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Lupine Publishers | Histochemical and Histomorphometrical Studies on the Digital Cushion of Heifers and Dairy Cows with Claw Horn Lesions

Abstract

Background: The ruminant claw horn lesions seriously diminish histological structure and functional efficiency of the digital cushion of the dairy cows.

Objective: To investigate histological and histochemical properties of the digital cushion in the dairy cow with claw horn lesions, such as white line disease, sole damage and hemorrhage.

Results: The results showed that digital cushion loses its normal histological structure in claw horn lesions.

Conclusion: Further biochemical, physiological and feeding studies on the experimentally induced claw horn lesions are necessary to understand the nature of the events playing roles involving animal feeding in the development of the lesions, to develop new animal feeding strategies aiming to protect and maintain the normal structure of the digital cushion.”

Keywords:Protein Degradability; Goats; Intensive Feeding; Nitrogen Balance; Digestibility

Introduction

Lameness is one of the most important problems negatively affecting milk yield and animal welfare in modern dairy farming in high-performance animals. The cows with laminitis produce lower amount of milk [1-5]. Moreover, cyclic reproductive changes of these cows slow down [6] or cease because of anoestrus [7] or cystic ovarian disease [8]. Lameness is a major animal welfare problem because that it is a painful condition and causes to behavioral changes of the affected cow. A lame cow tends to display low mobility [9], to spend decreased daily feeding time and dry matter intake [10] and lying behaviour may be indicative [11]. In the dairy cow, claw horn lesions [CHL] constitute 65% of the total lesions causing to lameness [12,13]. Although possible roles of risk factors, such as claw conformation and trimming, animal welfare, management, feeding and housing have been evaluated in detail by previous researchers [14-17], pathophysiology of CHL is still unclear. Previous researchers [18,19] have suggested that CHL is arisen from traumatic lesions of the supportive tissues of the claw. Around the time of calving, increase of hoofase enzyme, oestrogen and relaxin secretions results in loosening and increased mobility of suspensor apparatus of third phalanx [19]. The bovine digital cushion locating under the third phalanx has a complex structure, which major part is constituted of fat tissue. The cushion comprises three cylindrical segments [axial, medial and abaxial segments] of adipose tissue surrounded by a thick connective tissue trabecules, those arranged in parallel to each other [20,21]. The pads of the bovine digital cushion play crucial roles in reducing the body load transferred to surface of sole via absorbing of substantial forces acting within the claw [22]. The biomechanical function of the digital cushion in distributing and attenuation of the load transferred to the base of flexor process of the distal phalanx have been well appreciated by previous researchers [21,23,24]. The aim of the present study was to determine histological and histochemical properties of the digital cushion in the heifers and primiparous, second and third parturitions, and multiparous dairy cows managed under similar feeding, housing and welfare conditions. The foot was chosen from the animals with CHL, such as white line disease, sole damage and haemorrhage, in order to define the histology and histochemical changes in the digital cushions of the animals.

Material and Methods

Animals

This experiment was approved by the Ethical Committee of Experimental Animal Production and Research Centre (2011/023) of Veterinary Faculty of Selçuk University. In the study, the 120-cadaver foot (totally 240 hooves) of Holstein heifers and cows were used as materials. The animals were culled because of moderate to severe CHL and lameness in one or more hooves. The claws of the animals with similar feeding, housing and welfare conditions were subjected to a detailed clinical examination prior to slaughter. Information on the age, number of parturitions, calving history and stage of lactation were and recorded, in addition to the clinical findings. Among the reasons given for culling were insufficient milk yield, lameness and infertility. The animals were divided into 5 groups, each consisted of 6 animals, as group I: heifers, group II: primiparous cows, group III: cows with second parturition, group IV: cows with third parturition, group V: multiparous cows with more than three calving. The first group animals were 20 months old averagely; other groups were between 2.6-6.2-year-old. After slaughtering, all the foot was cleaned, and lesions, such as discoloration, sole ulcer and hemorrhages were recorded, frozen at -20°C and kept until use for histological procedure.

Dissection of the Hooves and Obtaining Tissue Samples

Each foot was thawed. The soft tissues of the sole and heel of each hoof were separated following the horn had been removed, in order to fully expose the axial, middle and abaxial pads of the digital cushion (Figures 1A-B & Figures 2A-C) [18]. Axial pad of the cushion was totally removed, fixed in 10% phosphate buffered (0.1M pH 7.4) formal-saline and used for histological procedures.

Histology and Histomorphometry

The tissue samples were subjected to routine histological tissue processing. Briefly, the tissue samples were washed with tap water overnight, dehydrated in ethylene series, cleared in xylene and immersed in paraffin. The sections taken at 6μm were stained as follows; hematoxylin-eosin for investigating general histology and histological changes [25], safranin-O (SO) for histochemical properties of ground substance, alcian blue at pH 2.5 (AB 2.5) for staining acid mucins and mucosubstance, alcian blue at pH 4.0 (AB 4) for demonstrating carboxylated glucose aminoglycans in the ground substance, trichrome stain for Type I collagen fibres (Coll I) and other histological detail, Verhoef’s elastic fibre (EL) stain for EL fibers [26]. The specimens were investigated under light microscope equipped with digital imaging system and digital images were recorded. The images were analyzed with digital image analysis software (BS200 PRO-2005).

Statistical Analysis

The data obtained from the digital image analyses were analyzed statistically with one-way variance analysis (ANOVA) and Tukey’s pair wise comparison tests by using SPSS software 14.01 (Release 14.01 Licence No: 9869264).

Clinical findings of the animals prior to slaughter and results of postmortem gross examination of the foot Welfare and management of the animals included into the study were far from than satisfactory. The animals were housed on the concrete floor, under poor hygiene conditions, and claw trimming was irregular. The animals were mainly fed with corn silage, alfalfa, vetch and hay. Findings of the postmortem examinations of the foot showed that the animals suffered from CHL, such as sole ulcers, hemorrhage and folding, white line disease and sole erosions in one or more hooves. The highest percentage of the claws with CHL was in the multiparous cows, in the group 5. The groups 2 and 1 the group followed it respectively. The lowest lower CHL frequencies were found in the groups 3 and 4, and the frequencies of these groups were quite similar (P>0.05, Figure 3).Gross Macroscopic Findings of the Cushion SegmentsIn most of the claws with CHL, segmental structure of the digital cushion was diminished. The digital cushion tissues of the heifers (Group 1) were pale and softer, whereas in the cows with the increasing the parturition number, the tissues gained yellowish colour and relatively more brittle and fragile. The cushion segments were also smaller in the animals of the groups 4 and 5, aged and multiparous cows (Figures 4A & 4B).

Histological Findings

In general, the digital cushion pads of the animals were mainly formed of a loose connective tissue and unilocular adipose tissue. Adipocytes appeared as large cells with unstained cytoplasm in all of the used staining procedures (Figures 5-9). Fibrous connective tissue septa surrounded the loose connective and adipose tissues. There were striking structural differences in the histology of the digital cushion of heifers and calved cows. Loose connective tissue in the heifers, was replaced with adipose tissue in the primiparous cows, and fibrous connective tissue rich in collagen fibres in the third lactation cows. In the heifers and primiparous cows, adipocytes were seen as groups, whereas in the cows of the groups 3, 4 and 5, the cells were observed as individual cells and the cell groups consisting of small numbers of the adipocytes. Adipose tissue percentages of the groups are given in the Table 1. The highest adipose tissue percentage (21.55%) was in the heifers, group 1, and the value was significantly (P<0.001) higher than those of the other groups (Figure 3). The groups 3 and 4 displayed similar (P>0.05) adipose tissue percentages. The multiparous animals (group 5) had the lowest adipose tissue percentage (Figure 3). Type I collagenous fibres were seen as thick undulating bundles of the fibres darkly stained with aniline blue in trichrome stained sections (Figures 5A- 5E).

The heifers had significantly (P<0.001) higher type I collagen fibre percentage (27.82%) than those of the other groups those had quite similar (P>0.05) percentages (Figure 3). In AB pH 2.5 stained specimens, the AB positivity was mainly located in the ground substance around the connective tissue fibres, embedded in-between the adipocyte groups (Figures 6A-6C). The positivity was also stronger around the individual adipocytes and the groups constituted of small numbers of these cells. Percentage of the AB pH 2.5 stained ground substance was highest (2.08%) in the group 3 and group 2 followed it (1.96%), whereas the groups 1, 4 and 5 had quite similar (P>0.05) and significantly (P<0.01) lower values than those of the groups 2 and 3 (Figure 3). AB pH 4.0 mainly stained the similar ground substance regions with AB pH 2.5, around the connective tissue fibres, located around the adipocyte groups (Figures 7A-7D). Results of the histometrical investigations of the AB pH 4.0 stained specimens showed that the group 1 and group 4 had similar (P>0.05), and significantly higher (P<0.01) positivity percentages than those of the groups 2, 3 and 5 (Figure 3). In SO stained specimens, the positivity was very weak (Figures 8A-8C) in all groups. The positivity percentages of the groups were quite similar and there were no significant differences (P>0.05) between the groups (Figure 3). Elastic fibres were mainly found in-between the connective tissue trabecules surrounding adipocyte groups and tunica adventitia of the blood vessels, and seen as brownishblack, branching coarse and gently undulating fine fibres, in the sections stained with Verhoeff’s elastic fibre stain (Figures 9A- 9E). The results of digital image analyses showed that the group 2 had the highest (1.89%) elastic fibre percentage and the value was significantly (P<0.05) higher than those of the other groups. The groups 1and 3, and 4 and 5 had quite similar elastic fibre percentages (P>0.05, Figure 3).

Discussion

In the present study, statistically significant (P<0.01) differences were found between the CHL frequencies of the groups. Particularly, high incidences of CHL in the primiparous cows (45.80%, group 2) and multiparous (56.20%) cows (group 5) were striking. The differences possibly have arisen from higher incidence of CHL in more than one or all foot of the animals in these groups. Previous researchers [27,28] have reported that the histological development and functional maturation of the digital cushion are not completed before the age of three, and also incidence of sole lesions, such as sole ulcerations and white line disease are relatively higher in the first lactation because that the cushion tissues is less elastic and rich in saturated fatty acids. In accordance with the previous researchers [27,28] Incidence of CHL was higher in primiparous cows in the present study. The roles of the additional loads and forces exposed at late pregnancy, and structural and biochemical changes in the regional tissues, in addition to trauma of both corium of sole and the cushion tissues in the pathogenesis and occurrence of CHL have been discussed in detail by previous researchers [17-19,29,30]. Moreover, collaborative effects of improper, inadequate feeding and housing practices are mentioned among significant disposing factors. In coordination of anatomic structures of the hoof [bones, joints, ligaments and bursae] leads to CHL, mainly sole ulcers and white line disease. Thus, hoof problems occur more commonly among the cows kept in cubicles or concrete yards or straw yards than in the cows kept in cowsheds. Previous researchers [18,31,32] have reported that lameness incidence increases in multiparous cows with increase of ageing and calving, especially after third lactation, due to increasing the amount of the loose connective tissue while reducing adipose tissue, decreasing body condition score [BCS], thinning of the cushion segments. In the present study, a gradually decline was found in adipose tissue percentages of the groups, with ageing and increasing parturitions. Loosening of suspensor ligament system of the hoof results in increasing in mobility of bones, and this situation disposes the sole corium and sole horn to traumatic lesions, and consequently plays significant roles in the development of CHL, such as sole ulcers, white line disease [19,33]. Loosening of suspensor system of the hoof also increases the sensitivity of the claw to the CHL depending on increase of loads applied to the foot by increase in mammary gland and foetus weights, especially during first lactation [34]. Clinical findings and histometrical results of the hooves and higher CHL incidence of the groups 2 and 5 are consistent with previous findings [18,31,32]. Moreover, higher CHL incidence of the group 5, in which significant shrinkage of the cushion tissue was observed, supports the hypothesis suggesting the decline in load absorbing capacity of the cushion increases risk of injury of sole corium. Thus, environmental factors, such as long time standing on the concrete floor, unsuitable housing conditions and in proper claw trimming are effective in embodiment of the sole trauma and haemorrhages in addition to increase of coffin bone motility in late pregnancy and parturition. Unsuitable housing and hygiene conditions in the animals of the present study were in accordance with the high CHL incidence of the animals.

The digital cushion, which is a specified connective tissue, is constituted of connective tissue cells and intercellular substance [ICS]. The ICS contains collagenous, elastic and reticular fibres embedded in an amorphous ground substance. The amount of the amorphous ground substance in young animals is higher than fibrous elements. With ageing, the amount and rate of fibrous elements increase and the rate reverses in older animals. The digital cushion, a member of supporting system of the ruminant hoof locating in subcutis, is a complex structure, composed of white and yellow adipose tissues. There are significant differences in histological structure and organization of the digital cushion among the ungulate animal species. The digital cushion of the ruminant hoof is closely resembled with the cushion of the elephant’s cushion [18]. Equine digital cushion has relatively different structural features. In the horse, the cushion is composed of small number of elastic fibres and closely packaged interlacing collagenous fibres dispersed in acidic mucous matrix, rich in hyaluronic acid. Large spaces between the cells and fibres occupied with mixoid tissue and islets of fibro cartilage tissue [35,36]. Collagen fibres, especially type I fibres are the dominant fibre type of the connective tissues. Although the collagenous fibres have limited elasticity, their tensile strength is enough to meet the high tensile forces of the foot. In the present study, axial pad of the digital cushion constituted of white, unilocular adipose tissue lobuli surrounded by connective tissue trabecules. Fibro cartilage was not observed in the specimens. In some of the groups, trabecules surrounding adipose tissue lobuli constituted of loose connective tissue and contained less amount of type I collagen fibres, the others were rich in the collagenous fibres. Group 1 contained significantly (p<0.001) higher collagen (27.82%) when compared with the other groups. A gradual decline of type I collagenous fibre percentage was typical in the remaining, older and multiparous groups (groups 3, 4 and 5). Nevertheless, they contained quite similar (P>0.05) type I collagen fibre rates. Gradual reduction of type I collagenous fibre rate with the increase of age and calving might arisen from the structural and functional changes occurred in aged animals and during the late pregnancy and post parturition. It might be predicted that shock absorbing capacity of the digital cushion considerably reduced with declining of collagen fibre rate. In accordance with this prediction, the highest (56.20%) CHL incidence was found in the group 5, which had relatively low rate of type I collagen fibres. Moreover, in accordance with the prediction above, previous researchers [19,33,37], also suggested that loosening of the suspensor system of the hoof during pregnancy and post parturition increases sensitivity of sole corium located between coffin bone and sole to trauma, and consequently playing significant roles in the pathogenesis of the CHL, such as sole ulcers and white line disease.

Although the information on the types and distribution of adipocytes in ruminant digital cushion is limited, the heifer cushion contains lesser amount of the fat cells. The digital cushion of the heifers is a whitish and gelatinous in nature containing high amounts of ground substance and lipid content gradually increases through 2-3 parturitions, and gradually decrease starting from 3 years of age [18,21,32]. Because that white fat tissue is an energy source, many metabolic and hormonal mechanisms, such as pancreatic hormones and glucocorticoids are efficient on this fat tissue. Thus, feeding and other metabolic factors are likely to efficient on both amount and composition of fat of the digital cushion. Moreover, it is well known that the fatty acid composition and amounts of the cow’s digital cushion are seriously affected by metabolic disorders, mainly by ketosis. Similarly, previous researchers [38] emphasized that the topic needs detailed evidences. In the presented study, the digital cushion of the dairy cattle comprised of islets of large unilocular adipocytes. In the digital cushion with low levels of fat tissue, individual adipocytes were frequently seen. The animals in the group 1 contained significantly (P<0.001) higher adipocyte rates (%21.55) and the group 2 it, with a significant decline. However, the group 2 contained significantly (P<0.05) higher fat tissue percentage than those of the groups 3, 4 and 5. Rastani [39] suggested that lipids are mobilized from fat tissues in order to be used in milk synthesis. Lipids in white fat depots in the digital cushion are also consumed. Considering the data obtained in this study, it is possible to assume that white adipose tissue in the ruminant digital cushion also can be used as an energy source in ketosis, which is a condition resulting in negative energy balance [NEB], and thus CHL increase post parturition period. It is well known that fat and elastic fibres of the digital cushion play significant roles in shock absorbing mechanism of the cushion via expanding sideways until their viscoelasticity is limited by stretched fibrous connective tissue septa rich in collagen fibres. Elastic fibres support expansion by flattening their undulations and support reversing to the situation before when the applied force is expired. Significant decreases in both elastic fibre and adipose tissue rates result in loss of elasticity of the digital cushion.

There is limited information on the histochemical properties of ground substance of the cow’s digital cushion, and also histometrical results evaluation of these parameters have not been documented previously. In the present study, the results of the AB pH 2.5, AB pH 4.0 and SO stains showed that ground substance of the cow’s digital cushion was rich in hyaluronic acid (hyaluronan) and other proteoglycans, although there were some differences between the groups. Because that hyaluronic acid is a macromolecule increasing the viscosity of the tissue fluid, it consequently augments resilience of the tissue by binding water molecules. Other proteoglycans stained with SO might support the digital cushion in resisting to pressure, since the proteoglycans also show high water binding affinity and tend to gelation [40]. Although the results of the present study indicated that the ground substance of cow’s digital cushion was rich in hyaluronic acid, the hoof material was obtained from the animals with varying degree of CHL lesions. The authors strongly stress that a detailed comparison should be carried out between the findings of healthy and CHL animals. The elastic fibres, which relatively thinner when compared to the collagen fibres, are able to compensate the forces applied between elasticity limits. Tissues gain elasticity and stress bearing features by their elastic fibre content. Elastic fibres are found in hoof soft tissues as in other elastic tissues. Information on distribution and localization of these fibres in the ruminant hoof soft tissues is insufficient. In a previous histological study [38], elastic fibres were found between the collagen fibre bundles in the digital cushion of African elephant. In this study, elastic fibres were more peculiarly observed in-between the collagenous fibre bundles and in blood vessel walls. Morphometrical analyses evidenced that the group 2 displayed significantly (P<0.05) higher elastic fibre percentage (1.89%) than the other groups. Although there was a declining tendency with increase of the parturition number, the other groups had relatively similar elastic fibre ratios. Besides, striking decline of the elastic fibre percentage was determined in the groups 4 and 5 in concomitant with higher CHL lesion incidence. Although further studies are needed, the results of the present study imply that elastic fibre content of the cow digital cushion is quite limited and might play only small role in the functions of the digital cushion and in the development CHL lesions.

Conclusion

Based on the results, it was concluded that CHL seriously affected both histology and functional efficiency of the digital cushion of dairy cows. Results of the present study, which show strong evidence between histological, histochemical and histometrical findings and CHL lesions are noteworthy. However, the results should be compared with those of the healthy animals in further experiments those are involving experimental models. Further studies necessary to understand the nature of the events playing roles involving animal feeding in the development of the lesions, to develop new animal feeding strategies aiming to protect and maintain the normal structure of the digital cushion, in order to maintain and augment its supportive and protective roles, to reduce incidence of laminitis.

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Lupine Publishers | Effect of Diet on Evolutionary Obstetrics

Opinion

Diet and health are both related directly to the reproductive functions of a female in that nutrient intake effects exactly what hormones are produced and at what amounts. According literature women of Western societies produce more progesterone and estradiol from their ovaries leading to high rates of breast cancer in the West [1]. Another facet to the Western diet is foods that are rich in sugar thus contributing to the blood sugar level and ultimately affecting resistance to insulin. This resistance to insulin, which is called diabetes, may lead to many problems of the reproductive function of women. Obesity, insulin resistance, and hyperinsulinemia are all common of women in the West and lead to oligomenorrhea, amenorrhea, and chronic anovulation [2]. Regions pay big role into nutrition in the sense that different areas have abundance of different types of foods, a bulk of North America simply gets absorbed into the “western” diet, meaning increased intake of unhealthy food due to increased availability of fast food. Since these female populations are adopting nutritious lifestyles leading to obesity, insulin resistance, and hyperinsulinemia, these newly developing populations have women who are unable to reproduce as well, thus making this “developing society” not “develop.” The current research is supported with case studies demonstrating insulin levels, SHBG, and testosterone levels of women who are of south Asian descent living in affluent societies such as the United Kingdom [3]. The evidence provided portrayed that though there were two type of women living in the same society, women from south Asia that were adopting the new Western lifestyles were more susceptible to having high levels of insulin and insulin resistance, thus proving that the societies that are westernizing is leading to reproductive failure of the women. What this portrays is that high levels of obesity, insulin resistance, and insulin itself leads populations in transition to have reduced fecundity in women and based on the examples provided, it is a logical conclusion [4].

Another, “purposeful” way of preventing pregnancy is to take oral contraceptives or using contraceptives altogether before having sexual intercourse. There are many different types of ways a woman who is sexually active can prevent pregnancy. The most recent type of contraception is the menstrual-suppressing oral contraceptives which lead to virtually no menstrual cycle or a very consistent menstrual cycle like one every 3 months [5]. The basis of the menstrual cycle is avoided because of the menstrual suppressing oral contraceptives. The main reason this happens is to procure sexual development and gain levels in estrogen and progesterone. There are two general standpoints on whether these contraceptives should be taken: the fact that the menstrual cycle is physiologically tolling, or menstruation is energetically less costly than maintain the endometrium between ovulations [6]. There are many different hypotheses present, after these standpoints are mentioned, which talk about what menstruation can do and why it is there. These hypotheses are that menstruation was an evolutionary byproduct, it aids in pathogen removal, it weeds out defective embryos, and it advertises fertility. How women feel about menstruation also would aid in decisions on whether to use contraception or not. According to the surveys, women are inadvertently split close to even in that some women feel they need the period and some feel that they should take oral contraceptives to ease the pain and reduce bleeding that occurs [7]. There are various pros and cons when considering oral contraceptives, so it is completely a woman’s choice on to take one or not. The menstrual cycle is neither beneficial nor deleterious when compared with women taking contraception, thus leaving the argument open ended on whether taking these contraceptives are viable. Poor diet garners an overall unwanted experience while contraception is used for the sole purpose of deterring pregnancy; these are two of the few ways that women are preventing pregnancies [8].

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Lupine Publishers | Women in Advertisements: Women or Objectified Thin Bodies?

Abstract

Since the beginning of Humanity history, women are one of the main focuses of attention. Women have to deal with beauty standards which are dynamic and are changing over time. Thus the actual beauty standard is very thin: to be beautiful, women have to be very thin. But women bodies in ads are retouched and unrealistic. Hence, when women with real bodies are confronted to thin-ideal bodies, they are, in fact, confronted to an unattainable standard of women beauty. By now, many findings suggest that repeated exposure to such unrealistic standards have negative and significative implications on women. Some of these effects could certainly be avoided if individuals, and especially women, were better informed about the unrealistic and harmful nature of this norm and its consequences.

Keywords: Objectivation; Thin Ideal; Advertisements; Women

Introduction

Since the beginning of Humanity history, women are one of the main focuses of attention. They have a lot of duties; have to adopt specific behaviors and to be good mothers and good wives. Specifically, women’s bodies are, since several decades, in the spotlight too. Women have to deal with beauty standards which are dynamic and are changing over time. With the apparition of mass media, the social pressure doesn’t only come from pairs and parents but also from media [1]. By now, mass media is considered as the most powerful and persuasive source of influence [2-4] as they are constantly surrounded by advertisements even when we do not necessarily pay much attention to Most ads (whatever the promoted product) use women bodies which depict the ideal norm of feminine beauty. Women in ads are presented as perfect, thin, beautiful, with smooth skin, very white teeth and unrealistic measurements [5]. Since the 1980s to the 1990s, we observe a significant decrease in the weight of female models [6] as models are now mostly underweight. Thus the actual beauty standard is very thin: to be beautiful, women have to be very thin. But women bodies in ads are retouched and unrealistic. Hence, when women with real bodies are confronted to thin ideal bodies, they are, in fact, confronted to an unattainable standard of women beauty. By now, many findings suggest that repeated exposure to such unrealistic standards have negative and significative implications on women. By setting what is appreciable or desirable in a woman [7], standards provide women with indicators to assess their own bodies. Social comparison with the weight standard contributes to the construction of women’s image of their own bodies [8] and since the standard is excessively thin , many women overestimate their weight, and even perceive themselves as overweight when they are objectively not [9]. Moreover, a perception of excess weight lead women to suffer from “normative discontent” [8] and a body dissatisfaction [10,11] which can affect women’s quality of life by generating low self-esteem [12], anxiety and even depression [13] and a greater accessibility of suicidal thoughts [14]. It also generates negative behavioral consequences: women who are dissatisfied with their bodies tend to use fast, harmful and unhealthy weight loss eating and physical practices [15], and weight overestimation predicts the use of behaviors that lead individuals to gain weight [16-19].

Conclusion

In addition, the thinness standard makes overweight synonymous with normative deviance. People who are overweight are the target of stereotypes: they are suspected of eating in secret, refusing to control their diet, losing control of themselves when eating, and over-consuming [20-22]. Overweight women are specifically considered as not being feminine and sensual [23]. Moreover, overweight individuals experience significant stigmatization [23-25] which obviously affects their quality of life and food behaviors. It also may also lead women who perceive themselves as overweight to make poor food choices and to consume more fatty and sweet foods through stereotype threat [25,26]. Some of these effects could certainly be avoided if individuals, and especially women, were better informed about the unrealistic and harmful nature of this norm and its consequences. Unfortunately, only a few are. We believe that public policies should address this limit and provide women the key elements to limit the negative consequences of exposure to the slimming standard, particularly in advertising.

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Lupine Publishers | Palauamine and Olympiadane Nano Molecules Incorporation into the Nano Polymeric Matrix (NPM) by Immersion of the Nano Polymeric Modified Electrode (NPME) as Molecular Enzymes and Drug Targets for Human Cancer Cells, Tissues and Tumors Treatment under Synchrotron and Synchrocyclotron Radiations

Editorial

In the current editorial, we study Palau’amine and Olympiadane Nano molecules (Figures 1 & 2) incorporation into the Nano Polymeric Matrix (NPM) by immersion of the Nano Polymeric Modified Electrode (NPME) as molecular enzymes and drug targets for human cancer cells, tissues and tumors treatment under synchrotron and synchrocyclotron radiations. In this regard, the development of Chemical Modified Electrodes (CEMs) is at present an area of great interest. CEMs can be divided broadly into two main categories; namely, surface modified and bulk modified electrodes. Methods of surface modification include adsorption, covalent bonding, attachment of polymer Nano films, etc. Polymer Nano film coated electrodes can be differentiated from other modification methods such as adsorption and covalent bonding in that they usually involve multilayer as opposed to monolayer frequently encountered for the latter methods. The thicker Nano films imply more active sites which lead to larger analytical signals. This advantage coupled with other, their versatility and wide applicability, makes polymer Nano film modified electrodes particularly suitable for analytical applications [1–27].

Electrochemical polymerization offers the advantage of reproducible deposition in terms of Nano film thickness and loading, making the immobilization procedure of a metal–based electro catalyst very simple and reliable for Palau’ amine and Olympiadane Nano molecules–encapsulating Carbon nanotubes incorporation into the Nano Polymeric Matrix (NPM) by immersion of the Nano Polymeric Modified Electrode (NPME) as molecular enzymes and drug targets for human cancer cells, tissues and tumors treatment under synchrotron and synchrocyclotron radiations. Also, it must be notice that the nature of working electrode substrate in electro preparation of polymeric Nano film is very important, because properties of polymeric Nano films depend on the working electrode anti–cancer Nano materials. The ease and fast preparation and of obtaining a new reproducible surface, the low residual current, porous surface and low cost of Multi–Walled Carbon Nanotubes (MWCNTs) paste are some advantages of Carbon Paste Electrode (CPE) over all other solid electrodes [28–92].

On the other hand, it has been shown that, macrocyclic complexes of Palau’amine and Olympiadane Nano molecules– encapsulating Carbon nanotubes are interest as modifying agents because in basic media Palau’amine and Olympiadane Nano molecules–encapsulating Carbon nanotubes redox centers show high catalytic activity towards the oxidation of small organic anti-cancer Nano compounds. The high–valence species of Palau’amine and Olympiadane Nano molecules–encapsulating Carbon nanotubes seem to act as strong oxidizing agents for low-electroactivity organic substrates. 1,2–Dioxetane (1,2– Dioxacyclobutane), 1,3–Dioxetane (1,3– Dioxacyclobutane), DMDM Hydantoin and Sulphobe as the anti–cancer organic intermediate products of methanol oxidation as well as formic acid, is important to investigate its electrochemical oxidation behavior in Palau’ amine and Olympiadane Nano molecules-encapsulating Carbon nanotubes incorporation into the Nano Polymeric Matrix (NPM) by immersion of the Nano Polymeric Modified Electrode (NPME) as molecular enzymes and drug targets for human cancer cells, tissues and tumors treatment under synchrotron and synchrocyclotron radiations [93–110].

In this editorial, we decided to combine the above mentioned advantageous features for the aim of Palau’ amine and Olympiadane Nano molecules–encapsulating Carbon nanotubes incorporation into the Nano Polymeric Matrix (NPM) by immersion of the Nano Polymeric Modified Electrode (NPME) as molecular enzymes and drug targets for human cancer cells, tissues and tumors treatment under synchrotron and synchrocyclotron radiations. Furthermore, in this editorial, we prepared poly Nano films by electropolymerization at the surface of Multi-Walled Carbon Nanotubes (MWCNTs) paste electrode. Then, Palau’amine and Olympiadane Nano molecules–encapsulating Carbon nanotubes were incorporated into the Nano Polymeric Matrix (NPM) by immersion of the Nano Polymeric Modified Electrode (NPME) in a solution. The modifier layer of Palau’amine and Olympiadane Nano molecules–encapsulating Carbon nanotubes at the electrode surface acts as a Nano catalyst for the treatment of human cancer cells, tissues and tumors under synchrotron and synchrocyclotron radiations. Suitability of this Palau’amine and Olympiadane Nano molecules–encapsulating Carbon nanotubes–modified polymeric Multi–Walled Carbon Nano tubes (MWCNTs) paste electrode toward the electrocatalytic treatment of human cancer cells, tissues and tumors under synchrotron and synchrocyclotron radiations in alkaline medium at ambient temperature was investigated [111– 153].

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Lupine Publishers | Battle Against Solid Waste: Contribution of University Belt Barangays Towards Clean and Disaster-Prepared City

Abstract

Solid waste is one of the major problems in the urban communities due to congestion and improper garbage disposal. This problem may lead to some health and disaster-related issues. University Belt Area (UBA), a congested place in Manila City, Philippines generate tons of solid waste materials daily. Given this condition, it is significant to know the response of the local government units (LGUs) in addressing this type of problem. Thus, this study investigated the solid waste management programs (SWMP) implemented by UBA barangays and its problems encountered in implementing the said programs. The awareness of the residents on SWMP and their suggestions for effective implementation of these programs were also determined. An in-depth interview was conducted among barangay officials. Small group discussion (SGD) was conducted among the selected residents. Thematic analysis was used to interpret the qualitative data while descriptive statistical tools were used to analyze the quantitative data. Findings revealed that programs implemented by ten barangays in UBA are categorized into educational, infrastructure, waste reduction, and regular cleaning activity. These programs are known to most of the residents who participated in the study. In the process of implementation, the LGUs are facing some constraints. These constraints include lack of discipline among the residents, lack of funds, irregular collection of waste materials, location of the barangay, and poor segregation practices. To effectively implement the afore-mentioned programs, the residents suggested some important recommendations. These encompass implementation of the appropriate barangay resolutions, raising public awareness, and imposition of penalties for the violators. Stakeholders should provide strong support for SWM agenda of UBA barangays. Policy makers should consider these data to formulate sound policies which can address the problems on solid waste. The barangay council should review Republic Act 9003 and consider collaboration with Ferris Wheel Project for better implementation of the programs.

Keywords: Barangays; Solid waste; Solid waste management programs; University belt area; Urbanized areas

Introduction

Every day the world is getting more urbanized. The rate of urbanization is increasing at an alarming rate. United Nations Department of Economic and Social Affairs (UNDESA) reported that 34% of the world’s total population in 1960 was living in the urban centers. In 2014, this rate increased to 54% [1]. This increase in urban population is brought by the natural increase due high fertility rate of the urban population and rapid rural to urban migration [2]. The rapid rate of migration is attributed to the pull factors inherent to the urban environment itself [3] like better job opportunities, access to health and educational facilities, and high standard of living. University Belt (U-Belt) area (Figure 1) in Manila, Philippines (Figure 2) is an area where colleges and universities are concentrated, hence the name implies. This area is the home of more than fifty higher educational institutions. The Central University Belt (CUBE) area is a seat for twenty universities and colleges. As Filipinos put a high regard for quality and responsive education, population over in this place has increased tremendously. This rise in population then is considered as contributing factors in the escalation of the amount of waste materials generated in the urban setting. According to National Solid Waste Management Commission Reports (2015). the estimated the amount of solid waste generated in 2010 in Manila City alone was 2,990,814 metric tons. In 2014, this figure increased to 3,595, 593 metric tons. There is, however, no specific information that pertains to the case of U-Belt area.

The rise in population in the U-Belt area also resulted to the emergence of additional commercial establishments, dormitories, and other infrastructure development. This infrastructure development resulted to changes in the land use and the increase in the urban surface sealing which increases the amount of surface run-off and decreases the ground water recharge [4]. This condition serves as a challenge to the Local Government Units (LGUs) on how to deal with this problem. The problems on improper waste management and high percentage of impermeable land make U-Belt area highly vulnerable to the devastating effects of flood. High amount of waste materials and improper disposal of these items make people highly prone to the diseases (National Solid Waste Management Commission Reports, 2015) [5]. From the prevailing condition of this place, the researchers came up with the framework on the goals of the implementation of solid waste management programs in U-Belt area (Figure 3). The current modified framework focuses on how the dirty, disaster-prone, and disorder U-Belt area can be converted into clean, disaster-prepared and orderly place (Figure 1). This framework was modified from the framework of Discipulo [6] on urban renewal study.

From the existing problems on solid waste management in the U-Belt area, this study investigated the contribution of the U-Belt barangays towards a clean and disaster-prepared city. Specifically, this study determined the solid waste management programs implemented by the barangays around the University Belt, identified the problems encountered by the communities pertaining to the implementation of the programs, determined the awareness of the residents in the said programs, and identified the suggestions of the residents for effective solid waste management programs implementation. Data obtained from this study is vital in policy making and urban planning of LGUs. This will also agitate the stakeholders to support and participate in the program implementation.

Materials and Methods

Research design

The research design employed both descriptive and qualitative approaches. Qualitative research aims to interpret meanings, descriptions, and symbols [7]. The goals of this type of research are to provide answers to the why’s and how’s. On the other hand, descriptive approach was used to describe characteristics of the population being studied [8]. This approach answers the question of “what” in the study. Objectives 2 and 4 were answered using qualitative approach while objective 3 was answered using descriptive method. Both qualitative and descriptive approaches were used to answer objective 1.

Research locale

The study was conducted in the U-Belt area. The name was given to this area because of the high concentration of the colleges and universities in this place. Originally, this name was given only to San Miguel district but technically it includes the nearby districts such as Quiapo, Santa Cruz. This area covers Mendiola Street, Morayta Street (now Nicanor B. Reyes Street), eastern end of Azcarraga Street (now Recto Avenue), Legarda Street, western end of España Boulevard, and the different side streets (Figure 4). This study covers the 10 barangays as given in Table 1.

Respondents of the study

The participants of the study were the 7 chairperson, 3 barangay councilors, and randomly selected residents of the ten barangays in the U-Belt Area. Ten barangay chairpersons and several barangay councilors were asked about the solid waste management programs implemented by their respective barangays and the problems they encountered during the implementation of the said program in an in-depth interview. The councilors interviewed in this study were the heads of the committee on health and sanitation. Selected residents were asked about their awareness on solid waste management programs of their respective barangays and their recommendations for effective implementation of the said programs during the small-group discussion (SGD).

Research instruments

Two research instruments were used to gather the data needed in this study. These instruments were the interview guide questions for in-depth interview and guide questions for small group discussion. The contents of these instruments were validated by the experts in the field of research and solid waste management.

Data collection procedure

In order to gather the data needed for the study, the researchers did an in-depth interview with the barangay chairpersons and barangay councilors, focus-group discussion with the randomly selected residents, and regular observation was also conducted to validate the results. The methods in the in-depth interview and small group discussion were patterned from the suggestions of Yukalang et al. [7]. The items in the questionnaires were based from the ideas of Yukalang et al. [9] and McAllister [10].

In-depth interview

An in-depth interview with eight barangay captains, 1 barangay councilor, and 1 barangay secretary was conducted by the researchers to determine the solid waste management programs implemented by the barangays around the U-Belt area and the problems encountered by the communities in the process of implementation of the said programs. The researchers prepared the guide questions for interview ahead of time. The guide questions were validated by the expert in the field of research and environmental issues and concerns. The English version of the guide questions was translated into Tagalog so that the respondents can understand better and they can freely engage in the conversation. The researchers asked permission to record the conversations from the barangay captains, barangay councilor, and barangay secretary. Field notes were also utilized to record pertinent information during the interview.

Small group discussion

Eight small group discussions were conducted during the duration of the study. The number of participants and date of discussion in the selected barangays in the U-Belt areas during the discussion are reflected in Table 1. The demographic profile of the participants such as age, occupation, and highest educational attainment were noted during the onset of the activity. Each participant was asked regarding his/her awareness about the implemented solid waste management programs in his/her barangay.

Observation

In order to counter-check the information disclosed by the barangay chairpersons and councilors, regular observations were conducted by the researchers. A weekly observation on the implementation of the solid waste management programs and the difficulties associated with the implementation of these programs was done from March to September 2017.

Data analysis procedure

After the collection of data, the data gathered were analyzed using descriptive statistical tools and thematic analysis. The quantitative data were interpreted using the descriptive statistical tools such as frequency counts and relative frequency. Meanwhile, the qualitative data were analyzed using thematic analysis. In this method, patterns or themes within data were identified, analyzed, and reported [7]. Patterns across data sets that are important to the description of a phenomenon and are associated to a specific research questions are referred as themes [11]. The themes generated from the data were validated by the experts in the field of research and solid waste management.

Results and Discussion

Solid waste management programs in the U-belt areas Results of the in-depth interview indicated that the programs implemented by ten barangays in the U-Belt areas are categorized into educational, infrastructure, waste reduction, and regular cleaning activity (Figure 5). Under educational programs, barangays implemented waste segregation campaign and information campaign. Also, they strictly imposed the “No segregation, No Collection Policy.” They also conducted the massive information campaign about proper ways of segregating of the waste materials as mandated by Republic Act 9003. Barangays are actively allotting budget for infrastructure which will counter the disaster which may be brought about by improper solid management. They have been allocating budget for repairing drainage system and constructing material recovery facilities. Material recovery facility serves as an area to store non-biodegradable materials prior to disposal.

In terms of waste reduction, barangays are now passionate in campaigning for the recycling activities. They encourage their residents to turn waste materials to raw materials for producing valuable products like lanterns and decorative stuffs. Regular cleaning activity, such as regular clean-up drive and street sweeping has been practiced by the local government units (LGUs) as a support to the solid management programs. The specific programs implemented ten barangays in the U-Belt areas is indicated in Table 2. Findings showed that out of ten barangays, seven of them, excluding barangays 395, 398 and 401 are currently implementing the clean-up drive program in their areas. Interestingly, ten barangays practice waste segregation program (Figure 6a). In addition, it was also revealed e that barangays 395, 396, 398 and 402 are implementing the Materials Recovery Facility (MRF) program (Figure 6b). Moreover, the results showed that barangays 395, 396, 397, 399 and 400 are active in implementing the information campaign program concerning the battle against solid waste. Barangay 400 is the sole barangay which is regularly doing drainage maintenance (Figure 6c). Findings also showed that all the barangays in the U-Belt are currently implementing a daily street sweeping activity (Figure 6d) in their barangays. Barangays 400 and 402 are the only barangays which are implementing the recycling activities in the University Belt (Figure 6e & Figure 6f).

Over the years rapid urbanization is taking place in Manila City, Philippines. This phenomenon was due to economic and social reasons. Consequently, the amount of waste materials generated also increases. Bernardo [12] showed that the households in the city generated an average of 3.2Kg of solid waste per day, or 0.50Kg/capita/day. In 2010, the estimated amount of solid waste generated in Manila was 2,990,814 metric tons and it increased to 3,595, 593 metrics in 2014 [4]. The existence of the different programs on solid waste management in ten barangays in the U-Belt area are the response of the various communities to the alarming problems associated with the elevating amount of solid waste generated in the congested communities. These programs are the manifestations that these barangays are abiding to the important provisions stipulated in Republic Act 9003, otherwise known as the “Philippine Ecological Solid Waste Management Act of 2000.

During the SGD, all participants were asked about their awareness on the programs implemented by the barangays in the U-Belt area on solid waste management. Findings of the investigation showed that 89% (31) of the participants are aware about the programs while 11% (4) participants are unaware (Figure 7). Generally, the results manifest that most of them have an idea about the implementation of the aforementioned programs. Awareness of the people about the programs is the outcome of the massive information drive and visibility of the infrastructure projects of the local government units. The high percentage of awareness on solid waste management programs among the residents in the U-Belt barangays is an indication that people are vigilant and participative in the programs and projects of the communities. Their participation ranges from attending the general assembly of the barangays up to abiding the proper segregation policy. On the hand, there are residents that remain not ware about the programs and policies of the barangays on solid waste management. Perhaps, they are not watchful regarding what is going to their communities and at the same time they are not participative to the activities of their barangays.

Constraints on solid waste management

Constraints encountered in the course of the implementation of every project and program makes the implementation itself very challenging. The problems encountered by the barangays in the U-belt areas in the implementation of the solid waste management programs are given in Figure 8. Findings showed that all ten barangays are currently facing the problem on the lack of discipline among the residents. They throw their garbage anywhere. They are particular of the designated places for their waste materials. Barangay 399 and Barangay 404 consider deficiency of funds as a major problem in the implementation of the program on solid waste management. Furthermore, it is also indicated above that 7 out of 10 barangays except for barangays 399, 402 and 403 are experiencing problem in terms of irregular collection of wastes. Findings also show that the barangays 395 and 397 are facing a problem on their location, which causes these barangays to produce more solid waste materials.

The constraints experienced by the U-Belt barangays in connection with the implementation of solid waste management programs in their communities are typical issues observed also in the other urbanized cities in the Philippines. For instance, Reyes & Arturo [13] observed several problems encountered by the community people in the implementation of solid waste management practices in the different barangays in Batangas City, Philippines. In their study, they found that the increasing population, inadequate government policies, public indifference (public don’t care), inefficient collection of garbage, rapid urbanization, non-operation of a good disposal facility, irresponsible government officials, lack of awareness among the people regarding the effects of solid waste management practices to their health and the environment, and lack of training on proper solid waste management practice are major barriers in implementing effective and efficient solid waste management programs.

In the developing countries however, there are constraints associated with solid waste management implementation. These constraints are categorized into culture, education, and microeconomics; infrastructure and technology; and policy, institutions, and macroeconomics [10]. In terms of culture, education, and microeconomics, the major constraints comprise the attitude and behavior gap of the people and lack of campaign on education and awareness. Major constraints under infrastructure and technology include budgetary constraints, inadequate service and operational inefficiencies, ineffective technologies and equipment inadequacy, lack of landfill disposal, and limited utilization of waste reduction activities. Under policy, institutions, and macroeconomics, the major constraints encompass lack of policy, poor enforcement and responsibility, and lack of monitoring and regulation.

Recommendations of the residents for effective implementation of solid waste programs

Some of the programs on solid waste management are not effectively implemented due to the political, educational, and socio-economic reasons. During the focus group discussion, the residents suggested some recommendations to the barangay officials for effective and efficient implementation of the solid waste management programs in the U-Belt Areas. These include implementation of the appropriate barangay resolutions, raising public awareness, and imposition of penalties for the violators.

Implementation of the appropriate barangay resolutions

One of the best strategies in order to ensure the effective implementation of the solid waste programs is to pass the appropriate barangay resolutions. The residents said that the existing resolutions are not enough to support the implementation of the aforementioned programs. Hence, the barangay council needs to pass some additional resolutions aside from “No Segregation; No Collection Policy.” These resolutions once passed should be disseminated to the general public. According to the respondents, in order for the residents to become fully aware of these resolutions, the council should ensure maximum attendance of the residents during the barangay assembly. In the era of rapid urbanization in the cities of the third world countries (e.g. Manila), appropriate policies should be implemented to address the problems associated with high urbanization growth [14]. In the case of the barangays in the U-Belt Areas, in order make solid waste management programs effective the policies and resolutions that may focus on allotting budget for the implementation of the programs, improving the linkages to the non-governmental organizations (NGOs), private sectors, and cause-oriented groups and proper spatial planning.

Raising public awareness

The success of the programs and projects on solid waste management strongly depends on the support of the stakeholders and the general public. The participation of these groups of people can be maximized if they have been properly informed. As revealed by the residents, the barangay should boost the awareness of the people through educational campaign and massive public information dissemination drive. The campaign for solid waste management programs in the U-Belt area can be disseminated well through posting in the bill boards and other public places. Campaign can be done during the barangay assembly; hence, the barangay officials should ensure the maximum attendance of the residents. Cultural and literary programs through songs and poetry can also be explored in order to boost the awareness of the people thriving in the U-Belt Area.

Imposition of penalties for the violators

According to the participants in the SGD, there is a need to impose penalties to the violators in order to make implementation of the solid waste management more effective. Violators, in the context of this study; refers to the residents who are not abiding with the policies and resolutions about management of solid waste. For instance, these people don’t dump their garbage materials in the right bins and throw their waste materials in bodies of water. Those who are doing such should be penalized by the barangay councils. The penalty could be letting them engage on community service or pay offenders can pay a certain amount of money. Community service, on the other hand, could include cleaning the public places such plaza, streets, and bodies of water and repairing of the drainage system. Imposing these types of penalties will create a culture of discipline and support among the residents.

The success of the implementation of solid waste management can be attributed by three major factors. These factors include people’s orientation and strong political leadership, strong collaboration among the different sectors of the community, mass information, education, and communication campaign, and linkage and networking with different agencies and organizations [15,16]. Mc Allister [10] considered potential interventions in order to implement solid waste management programs effectively and efficiently. These interventions include intensified education and awareness campaign, enhancement of public participation, promotion of the incentive scheme, improvements in service operations, improvements in the accessibility of the technologies, utilization of the recycling initiatives, improvements in disposal system, creation of landfill, enhancement in the funding management, and proper enactment and enforcement of the policies and programs.

Conclusion

The programs implemented by ten barangays in the U-Belt areas are categorized into educational, infrastructure, waste reduction, and regular cleaning activity. These programs are known to most residents of the area. In the process of implementation, the LGUs are facing some constraints. These constraints are: lack of discipline of among the residents: lack of funds: irregular collection of waste; location of the barangay; and lack of segregation. To effectively implement the aforementioned programs, the residents suggested some important recommendations. These include implementation of the appropriate barangay resolutions, raising public awareness, and imposition of penalties for the violators (Figure 9).

Furthermore, the concept of eco-city [17,18] should be integrated by the U-Belt barangays in their campaign for effective solid waste management programs. The idea of composting [19] in the urban setting like enzyme-enhanced compositing and vermicomposting [20-24] should also be considered for the aforementioned program. For the future research endeavor, a greater number of respondents should be considered. Hence, the entire University Belt area should be covered in the succeeding research activity. From the major findings acquired in this study, the authors came up with the extension program of SHS Department of UE Manila known as “FERRIS WHEEL PROJECT” (Figure10). It is a holistic, multi-sectoral, and multi-disciplinary project which aims to further raise the awareness of all sectors in the U-Belt community about problems associated with solid waste management. These sectors include business, youth, local government unit, academe, and people with disabilities.

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Lupine Publishers | Can Dimple on Face is Affected by Blood Group?

Abstract

The objective of the present study was to correlate dimples on face with blood group system in humans. Total 180 subjects were participated in this activity. The subjects were student at Bahauddin Zakariya University Multan, Pakistan. Blood is to be checked against three types of antibodies, antibody A antibody B and –Rh serum. I took the blood group of the subjects and checked their blood type. Then we made list of subjects with their blood group types and asked them do they have dimple on their face or not one by one. Then we mentioned whether they have dimples or not after their blood group type in the list. It was concluded from the present study that O+ blood group people have maximum chance of having dimples and AB- have minimum chance of having dimples.

Keywords: ABO blood group system; Face dimples; Dimples and Blood grouping

Introduction

The most important blood group system in human blood transfusion is ABO blood group system. It is also present in some other animals like chimpanzees, bonobos and gorillas. ABO blood group system is discovered by Karl Landsteiner who discovered three different blood types in 1900. Our blood contains white blood cells, red blood cells, platelets and plasma. A person with blood group A, he have antigen A on red blood cells surface and antibodies B on his blood plasma. On the other hand a person with blood group B have B antigen on red blood cells surface and A antibodies in his plasma. If he have blood type AB, then he have both antigen A and B on his red blood cells surface and no antibodies. If he has O blood group than neither he have antigen A nor B on red blood cells and both A and B antibodies present in plasma. A person having blood group A can donate blood to the person having blood group A. B blood group can only be donates to a person having blood group B and so on. If a person receive another type of blood or donate blood to a person with another type of blood than antibodies will match to the donors blood antigen. Red blood cells will clump in donated blood. Antibodies bind with the foreign red blood cells which cause agglutination.

Agglutinated red blood cells will break after a while and their content will leak out. Persons having AB blood are universal receivers and they receive blood from all blood groups. Persons with O blood group are universal donors and they donate blood to all types of blood groups. Rh blood group system is another and important blood group system after ABO [1]. Term Rh is abbreviation of “Rhesus factor” discovered in 1937 in rhesus monkey red blood cells. Rh blood group system related with many antigens, one of which is antigen D. Rh+ blood type have antigen but Rh- do not have antigen. Those individuals who lack antigen D do not make it naturally. Rh+ antigen lack the antigen and pose a danger for Rh- persons. Adverse effects may not be occur the after first time when blood with Rh+ is given to the person having Rh blood group. But the immune system produces anti Rh antibodies by responding to the foreign Rh antigen. If we give again Rh+ blood then after forming antibodies they cause agglutination because foreign red blood cells cause them to clump together. Hemolysis occur which cause destruction of red blood cells and also cause serious illness [2].

Dimple is a small hollow area on a part of human body mostly noticed on the cheek or on chin. There are two kinds of dimples, chin and cheek dimples. Cheek dimples shown when a person make a face expression. But in the case of chin dimple there is a small line on the chin that stays without making any face expression. Dimples may be appear or disappear for an extended period of time. Some researchers conclude that dimples are genetically inherited and as a dominant trait. But some said that they are irregular dominant trait controlled by one gene that may be influenced by some other genes. It is a genetic defect that cause irregular growth of certain facial muscles during embryonic development. They are formed by structural variation in facial muscle which is zygomaticus major. Presence of double zygomaticus major muscle form cheek dimples. The muscle that is shortened is responsible for stretching or pulling our lips behind into corners when we smile. They occur in those persons having dominant dimple gene. If both parents have dimples than there would be 50% chance that this deformity passed into next generation. Dimples are incredibly attractive and so many people wish that they could have dimples. If a person feels uncomfortable with their dimples than there are some ways to help them. They can never be removed but there are procedures that can reduce dimple size. The objective of present study was to correlate dimple on face with blood group system in humans.

Materials and Methods

Blood Grouping

In order to check blood group of any person, a blood sample is needed. First of all sterilize finger with alcohol wipes then take blood from fingertip by pricking it. Blood is checked by mixing it with three types of antibodies in test tube against Antibody A, Antibody B and anti-Rh serum. Cells clumps, or blood clotting tells about the type of Blood group. Then I Put blood group sample in test tube then add antibodies in it. After adding antibodies to blood sample wait for few seconds to observe precipitates formation. If blood is clot it means one of the antibody will react to the blood. If blood cells do not clot on antibodies A or Antibodies B then it is blood group O, If it clots on both antibodies A and B then Blood group is AB. If blood cells clot against Antibodies A then it is Blood Group B and if blood cells clot against Antibodies B then it is Blood Group A. After this blood sample is checked against anti-Rh serum which confirms the positivity and negativity of that blood group. Drop anti-Rh serum on blood sample if blood cells clot on Rh antibodies then blood group type is positive and if do not clot then it is negative blood group type.

Project Designing

Firstly, we took consent from each subject to take their blood sample and collected information by making questionnaire that do they have dimples on their face or not? Then we took blood sample of each subject and checked their blood group type by the procedure mentioned above. Then we made list of subjects with their blood group types and asked them do they have dimple on their face or not one by one. Then we mentioned whether they have dimples or not after their blood group type in the list. Total 180 subjects were participated in this activity. The subjects were students in Bahauddin Zkariya University Multan, Pakistan.

Statistical Analysis

MS Excel is used to perform statistical analysis.

Results and Discussion

Following Table 1 shows the percentage of dimples in A+ males is 11.76% while in A+ females is 20%. Percentage of dimples in both A- males and females is 0%. B+ males have 10% and B+ females 21.81% dimples. B- males and females both have 0% dimples. AB+ males have 0% dimples while AB+ females have 12.50%. AB both males and females have 0% dimples. O+ males have 16.66% and females have 26.83% dimples. O- males have 0% and females have 40% dimples on their face. Questionnaire based studies have given an important advancement in recent studies. Four scientists in 2015 work on five different Genetic Traits in Association with the Distribution Pattern of ABO and Rhesus Phenotypes among Families in Calabar and Nigeria one of which was dimples [3-10].

Conclusion

It was concluded from the present study that O+ blood group people have maximum chance of having dimples and AB- have minimum chance of having dimples.

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Lupine Publishers | The Optimal Pain Management Methods Post Thoracic Surgery: A Literature Review

Abstract

Post-operative pain control is one of the key factors that can aid in fast and safe recovery after any surgical interventions. Thoracic surgery can cause significant postoperative pain which can lead to delayed recovery, delayed hospital discharge and possibly increased risk of chest complications in the form of atelectasis and even lower respiratory infections. Therefore, appropriate pain management following thoracic surgery is mandatory to prevent development of such morbidities including chronic pain.

Keywords: Thoracic Surgery, Analgesia, VATS, Robotics, Thoracotomy

Introduction

Thoracic surgical procedures can result in severe pain which can present as a challenge to be appropriately managed postoperatively. In particular, thoracotomies are well known for their severity of pain due to the incision, manipulation of muscles and ligaments, retraction of the ribs with compression, stretching of the intercostal nerves, possible rib fractures, pleural irritation, and postoperative tube thoracotomy [1]. Recognition of this has contributed to the development of minimally invasive techniques such as video assisted thoracoscopic surgeries (VATS) and lately robotic surgery [1]. These techniques not only aim to produce better aesthetic results, but also reduce post-operative pain and enhance recovery without compromising the quality of treatment offered. Poor pain management can lead to several and serious complications such as lung atelectasis, hypostatic pneumonia due to avoidance of deep breathing in these patients as a result of pain and superimposed infection [1]. Pain management as a result, does not only lead to greater patient satisfaction, but it also reduces morbidity and mortality in patients undergoing thoracic surgery [2]. Historically, post-operative pain management for thoracic surgery involved the use of narcotics alongside parenteral or oral anti-inflammatory agents [2]. Post chest tube removal patients typically are transitioned to oral analgesia. Multiple additional pain control adjuncts were also implemented with differing levels of success [1]. Over time, intra-operative techniques have been developed which aims to target pain reduction postoperatively [2]. As our understanding of both pain management and the factors that play a role in the development of pain has increased, we have been able to target these and improve postoperative pulmonary morbidity and pain scores [1,2]. We aim to review different means of pain control in this paper in order to assess their effectiveness in achieving optimum results.

Thoracotomy

The mechanism of pain in thoracotomy involves the innervation of the intercostal, sympathetic, vagus and phrenic nerves [3]. Additionally, shoulder pain may result from stretching of the joints during the operation.

After a thoracotomy, pain can persist for two months or more, and in certain incidences it recurs after a period of cessation. The incidence of chronic pain post thoracotomy is reported to be 22-67% in the population [4]. Good surgical technique and effective acute post-operative pain treatment are evident means of preventing post-thoracotomy pain and consequent pulmonary complications [4]. Due to the multifactorial character of the pain, a multimodal approach to target pain is advised. Typically, both regional and systemic anaesthesia are administered. A combination of opioids such as fentanyl or morphine are typically used [5]. A variety of techniques for the administration of local anaesthetics are available at present, and the effectiveness of each is assessed in this paper.

a) Thoracic Epidural Analgesia (TEA)

TEA was the most widely used method of means of analgesia. It was the gold standard means of pain relief [6,7]. It is typically inserted prior to general anaesthesia, at the level of T5-T6, midway along the dermatomal distribution of the thoracotomy incision. A study by Tiippana et al. [8] measured the visual analogue scale (VAS) in order to assess the presence of pain during rest and at the time at which they coughed in 114 patients of whom 89 had TEA and 22 who had other methods of pain control. TEA was effective in alleviating pain at rest and during coughing. In TEA patients, the incidence of chronic pain of at least moderate severity was 11% and 12% at 3 and 6 months, respectively. The study found that at one week after discharge, 92% of all patients needed daily pain medication. The study advised for extended postoperative analgesia for up to the week post-discharge to be administered in order to manage this. The study however concluded overall, that TEA was effective in controlling evoked post-operative pain. However, the study did encounter problems of technical form in 24% of the epidural catheters. The incidence of chronic pain, however, was lower compared with previous studies where TEA was not used. Several other studies support that TEA is superior to less invasive methods. According to Shelley B. et al. [9] TEA was preferred by 62% of the respondents over paravertebral block (PVB) with 30% and other analgesic techniques with 8%. Limitations of this technique included hypotension and urinary retention. Certain patients with active infection and on anticoagulation are excluded from epidural placement.

b) Paravertebral Block (PVB)

PVB is considered an effective method for pain management and its use has been increased in the recent years. This technique involves injecting local anaesthetic into the paravertebral space and it is able to block unilateral multi-segmental spinal and sympathetic nerves. Previous studies have shown that it is effective in achieving analgesia and is associated with a lower incidence of side effects such as nausea, vomiting, hypotension and urinary retention [10,11]. As the lungs are collapsed, it is associated with a lower risk of pneumothorax.

In a study by Davies R.G. et al. [10] there was no significant difference in pain scores, morphine consumption and supplementary use of analgesia between TEA and PVB. The rate of failed technique was lower in PVB (OR =0.28, p=0.007). Respiratory function was improved at both 24 and 48 hours with PVB but only significantly improved at 24 hours.

c) Intercostal Nerve Block (ICNB)

ICNBs are generally administered as single injections at least two dermatomes above and below the thoracotomy incision [12]. It is performed percutaneously or under direct vision, using single injections or through placement of an intercostal catheter. It can also be formed using cryotherapy. It is associated with reduced post-operative pain scores; however, it is less effective than TEA in controlling chronic pain [12]. This was illustrated by a study by Sanjay et al. [12] which found that patients that underwent ICNB had higher pain scores 4 hours post-operatively, than those who received epidural anaesthesia using 0.25% bupivacaine (p<0.05). The study concluded that in the early post-operative period there was significant impact in pain relief for both techniques, but thereafter, epidural anaesthesia was proven to significantly reduce post thoracotomy pain over ICNB. Due to the multifactorial nature of post-thoracotomy pain, various approaches are required in order to target pain. ICNBs are useful in the blockade of intercostal nerves, whilst PVB and TEA appear to block the intercostal and sympathetic nerves. Due to the inability of regional anaesthesia to block the vagus and phrenic nerves which are implicated in the pathophysiology of pain, NSAIDs and opioids are required as adjuncts. TEA is proven to be the most effective means of treating pain alongside PVB; however, it is associated with more side effects than PVB. At present, there are a limited number of studies directly comparing pain control and post-operative outcomes between PVB and TEA. There is no conclusive evidence that either method is superior to the other regarding pain control.

Video-Assisted Thoracoscopic Surgery (VATS)

Existing evidence supports the noninferiority of thoracic PVB when compared to TEA for postoperative analgesia [13]. PVB is versatile and may be applied both unilaterally or bilaterally. It can be used to avoid contralateral sympathectomy, consequently minimising hypotension. This is an apparent advantage it has over thoracic epidural. Furthermore, it offers a more favourable side effect profile when compared to epidural anaesthesia. At present, the factors taken into consideration when selecting a regional technique include tolerance of side effects associated with TEA, consensus on best practice/technique, and operator experience [13]. A randomised controlled trial by Kosiński et al. [14] compared the analgesic efficacy of continuous thoracic epidural block and percutaneous continuous PVB in 51 patients undergoing VATS lobectomy. The primary outcome measures were postoperative static (at rest) and dynamic (coughing) visual analogue pain scores (VAS), patient-controlled morphine use and side-effect profile. The study found that pain control (VAS) was superior in the PVB group at 24 hours, both at rest (1.7 vs3.3, p=0.01) and on coughing (5.8 vs 6.6, p=0.023), and control of pain at rest was also superior in the PVB group at 36 hours (3.0 vs 3.7 (p=0.025) and at 48 hours (1.2 vs 2.0, p=0.026). There were no significant differences in the postoperative morphine requirements. In regard to side-effect profile, the study showed that the incidence of postoperative urinary retention (defined as no spontaneous micturition for 8 hours or ultrasound-assessed volume of the urinary bladder >500ml) was greater in the epidural group (64.0% vs 34.6%, p=0.0036), as was the incidence of hypotension (32.0% vs 7.7%, p=0.0031). There was no significant difference in the incidence of atelectasis (4.0% vs 7.7%, p=0.0542). However, the incidence of pneumonia was significantly more frequent in the PVB group (3.8% vs 0%, p=0/0331). Kosiński et al. concluded that PVB is as effective as thoracic epidural block in regard to pain management as it offers a superior safety profile with minimal postoperative complications. A further randomised controlled trial by Okajima et al. [15] compared the requirements for postoperative supplemental analgesia in 90 patients who received wither a PVB or thoracic epidural infusion for VATS lobectomy, segmentectomy or wedge resection. The main outcome measures were pain scores at rest (verbal rating scale 0= none and 10=maximum pain), blood pressure, side effects and overall satisfaction scores relating to pain control (1=dissatisfied and 5=satisfied). The study found a similar frequency of supplemental analgesia (50mg diclofenac sodium suppository or 15mg pentazocine intramuscularly) for moderate pain in both groups, with 56% of those in the PVB group requiring ≥2 doses, compared to 48% in the epidural group (p=0.26). Hypotension, defined as a systolic blood pressure <90mmHg, occurred more frequently in the epidural group (21.2% vs 2.8%, p=0.02). There was no difference in the incidence of pruritus (3.0% vs 0%, p=0.29) and post-operative nausea and vomiting (30.3% vs 25.0%, p=0.62) between both groups. The study found no statistical difference between patient-reported satisfaction in pain control between epidural and PVB using the verbal rating scale (5.0 vs 4.5, p=0.36). The study concluded that PVB offered additional to equivalent analgesia to epidural, a lower incidence of haemodynamic instability postoperatively. A further study by Khoshbin et al. [16] performed an analysis on 81 patients undergoing VATS for pleural aspiration +/- pleurodesis, lung biopsies or bullectomy. The main outcome was postoperative pain levels, documented every 6 hours and scored against the Visual analogue Scale (0= no pain, 10= worst possible pain). In both PVB and epidural groups, bupivacaine 0.125% was the local anaesthetic of choice, with clonidine added to the epidural infusion at 300μg in 500ml. The study showed that there was no significant difference in mean pain scores between PVB or EP (2.1 vs 2.9, p=0.899), therefore concluding that PVB is as effective as epidural in controlling pain post-VATS.

Robotic Lung Surgery

Minimally invasive techniques are considered advantageous over open surgical approaches due to their shorter recovery times, reduced perceived levels of pain post-operatively and shorter postoperative length of stay in hospital [17-19]. Robotic surgery has become a popular method in recent years. Debate remains regarding whether robotic surgery is superior to VATS in regard with pain reduction. A case control study by Louie et al. [19] compared 45 robotic assisted lobectomies (RAL) to 34 VATS lobectomies. The study showed that both groups had a similar mean ICU stay (0.9 vs 0.6 days) and a mean total length of stay (4.0 vs 4.5 days). The study showed that patients that underwent robotic lobectomies had a shorter duration of analgesic use post-operatively (p=0.039) and a shorter time resuming to normal everyday activities (p=0.001). A limitation in this study was an inaccurate record of the amount of pain relief used by the patients, ultimately working as a confounding factor when interpreting the results. In a separate study by Jang et al. [18] 40 patients undergoing RAL were compared retrospectively to 80 VATS patients (40 initial patients and 40 most recent patients), all with resectable non-small cell lung cancer. The study showed that the post-operative median length of stay was significantly shorter in RAL patients compared to the initial VATS patients. The rate of post-operative complications was significantly lower in the RAL group (10%) compared to the initial VATS group (32.5%) and similar to the recent VATS group (17.5%). Post-operative recovery was easier for patients in both the RAL and VATS group due to earlier mobilisation, allowing them to return to their everyday activities quicker. In a retrospective review by Kwon et al. [17] 74 patients undergoing robotic surgery, 227 patients undergoing VATS and 201 patients undergoing anatomical pulmonary resection were assessed and compared with regard to acute (visual pain score) and chronic pain (Pain DETECT questionnaire). The study showed that there was no significant difference in acute or chronic pain between patients undergoing robotic assisted surgery and VATS. Despite no significant difference in pain scores, 69.2% of patients who underwent robotic-assisted surgery felt the approach affected their pain versus 44.2% of the patients who underwent VATS (p=0.0330). These results all support the superiority of robotic surgery over VATS and open approaches with regard to pain, length of hospital stay and recovery times. Both robotic surgery and VATS have their benefits i.e. two-versus three-dimensional view, instrument manoeuvrability, and reduced post-operative pain.

Conclusion

Since post-thoracotomy pain is multifactorial, a multimodal approach is required. In particular, ICNB blocks the intercostal nerves, and PVB and TEA appear to block the intercostal and sympathetic nerves. NSAIDs and opioids are required as valgus and phrenic nerve cannot be blocked by regional anaesthesia. TEA is evident to be the most effective in treating pain alongside with PVB. It is however associated with more side effects than PVB.

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Lupine Publishers | Oral Agents in the Treatment of Inflammatory Bowel Disease: A Remarkable Progress

Abstract

Despite remarkable progress for management of moderate-to-severe IBD patients, there are significant rates of primary nonresponse, loss of response, and/or adverse events thereby necessitating additional treatment options. Additionally, the burden of intravenous administration or subcutaneous injection of biologics accompanied by associated high cost necessitate the development of alternative treatments. In recent years, remarkable research has focused on the development of oral small molecule agents. Fortunately, the rapidly growing number of targeted therapies with oral small molecule agents offer the advantage of ease of administration with the durable effectiveness and no downside of immunogenicity with relatively more safety profile compared to the FDA approved biologic agents with relatively lower cost in the management of patients with moderate-to-severe IBD. The purpose of this review article is to summarize available novel oral small molecule agents in treatment of patients with IBD. Two of the oral small molecule agents, tofacitinib and ozanimod were already approved by the FDA for patients with moderate-to-severe ulcerative colitis. We will not include other emerging therapeutic modalities such as microbiome targeted or stem cell therapies in this review.

Introduction

Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease are chronic relapsing disorders of intestinal inflammation which leads to decreased quality of life, disability, and bowel damage resulting in hospitalizations and surgeries [1]. Several genetic models have been developed for the inflammatory cascade that leads to the chronic inflammation seen in IBD, but none of these models have been able to account for all the observed pathophysiologic features. This complexity is probably secondary to the intricate nature of IBD and an incomplete understanding of the interactions between the mucosal immune system and the intestinal microbiota [2]. The current goal of treatment is to achieve clinical, endoscopic and histologic remission of disease activity. Management of IBD is generally divided into induction and maintenance phases. These phases involve achieving remission of inflammation quickly usually over a 2-3 month period and then maintenance of that clinical and histologic remission beyond that point Table 1.

5-ASA acts as a topical anti-inflammatory agent that has efficacy within the lumen of the intestine [3]. Although its use is well established in ulcerative colitis, its efficacy in its effect in Crohn’s disease is not better than placebo. Mild-to-moderate ulcerative colitis can be managed with oral 5-ASA treatments, but is not effective for moderate-to-severe disease. Older treatments for moderate-to-severe IBD include steroids and thiopurines including azathioprine, mercaptopurine, and methotrexate Table 2. Despite the efficacy of prednisone in improving acute symptoms of IBD patients, they have not consistently demonstrated effectiveness in controlling histologic inflammation. In addition, side effects related to long term use of steroids can be debilitating including but not limited to insomnia, personality changes, acne, fatigue, and weight gain. Alternative agents such as the oral controlled ileal release budesonide have been developed. Budesonide is efficacious in the management of inflammation in the terminal ileum and right colon. This makes budesonide effective for short-term relief of symptoms for mild-to-moderate IBD but not a good long-term option. The efficacy of thiopurines to maintain medically induced remission as well as to prevent post-operative recurrence in IBD has been well established. In the SONIC trial, the mucosal healing rate in patients in clinical remission was not significantly different between the azathioprine and anti-TNF monotherapy arms (36% vs. 43%) [4]. Despite their effectiveness many patients elect to stop thiopurine therapy. Up to 40 percent of patients discontinued thiopurine therapy in the first 4 months of treatment due to intolerance or ineffectiveness [5]. In addition, there is no doubt that thiopurines safety profile is inferior as there is a significant risk of developing lymphoma and non-melanoma skin cancer [6]. No satisfactory management of IBD was achieved prior to the development of infliximab. Current recommendations for the management of IBD with biologics include the use of early therapy with a treat-to target strategy to achieve clinical remission, mucosal and histologic healing which ultimately decrease the risk of corticosteroid use, surgeries, hospitalizations and increases quality of life [7]. Available biologic agents include anti-tumor necrosis factor alpha (TNF-a) agents including infliximab, adalimumab, certolizumab, and golimumab; anti-integrin agents including vedolizumab and natalizumab; and anti-interleukin (IL) 12-23 agents such as ustekinumab. Unfortunately, despite remarkable progress in the management of moderate-to-severe IBD patients, there are significant rates of primary non-response, loss of response, and adverse events, thereby necessitating additional treatment options. Additionally, the burden of intravenous administration or subcutaneous injection accompanied by associated high cost necessitate the development of alternative treatments. In recent years, remarkable research has focused on the development of oral small molecule agents Table 3. Unlike antibodies that can develop with biologic agents, oral small molecule formulations do not carry the same risk of immunogenicity. Their molecular characteristics and size allow for a more convenient oral administration and avoids the potential development of anti-drug antibodies. The purpose of this review article is to summarize available novel oral small molecule agents in treatment of patients with IBD. Two of the oral small molecule agents, tofacitinib and ozanimod were already approved by the FDA for patients with moderate-to-severe ulcerative colitis. This review will not include other novel and emerging therapeutic modalities such as microbiome targeted or stem cell therapies.

JAK Inhibitors

One of the new treatment strategies that has been developed is the targeting of the Janus kinase (JAK) family of tyrosine kinases [8]. The functions of this family of tyrosine kinases is broad, but evidence suggests that innate and adaptive immune responses require JAK-STAT signaling to mediate several pathways of cytokine function. These agents inhibit cytokines in the inflammatory cascade such as IL-9, IL-12, IL-23 and interferon-gamma. Several studies have supported this hypothesis by demonstrating significant upregulation of JAK transcripts in intestinal mucosa of patients with active ulcerative colitis [9]. These facts make targeting the JAK-STAT an appealing therapeutic modality in IBD. This has led to the development and regulatory approval by the United States Food and Drug Administration (FDA) of therapies targeting the JAK pathway for the treatment of IBD [10]. One of those therapies is a non-specific pan-JAK inhibitor tofacitinib, which was approved by the FDA in 2018 for the treatment of patients with moderateto- severe ulcerative colitis. The Octave trial which included the phase 3 clinical trial that led to the regulatory approval of tofacitinib for the treatment of ulcerative colitis included patients randomly assigned to 10 mg of tofacitinib twice daily or placebo for 8 weeks. Clinical remission (determined to be a Mayo Clinic score of less than 2 and a rectal bleeding score of 0) at 8 weeks occurred in 18.5% of patients assigned to tofacitinib versus 8.2% of patients assigned to placebo (P = 0.007) [11]. The Octave sustain maintenance study re-randomized week 8 responders to receive 10 mg or 5 mg of maintenance tofacitinib twice daily or placebo for 52 weeks. Remission at 52 weeks was significantly higher in patients treated with 5 mg (34.3%) and 10 mg (40.6%) of tofacitinib than with placebo (11.1%; p<0.001 for both comparisons with placebo). Notably, tofacitinib has a rapid onset of induction and has shown to be effective in refractory anti-TNF exposed ulcerative colitis patients compared to placebo [12]. Similar studies in patients with Crohn’s disease failed to achieve primary and secondary endpoints though there were modest improvements in inflammatory markers; this was probably due to the study design and unusually high placebo response rate seen in the study [13]. Clearly more research in the use of tofacitinib is needed to elucidate its efficacy in patients with Crohn’s disease. This data makes tofacitinib an attractive treatment option for patients with moderate-to-severe ulcerative colitis. However, tofacitinib can inhibit the immune system to a degree that increases the risk of herpes zoster, serious bacterial infections, tuberculosis, and upper respiratory tract infections [14]. The safety committee of the European Medicines Agency performed a review of tofacitinib due to the concern for an increased risk of developing pulmonary embolisms [15]. Subsequently, the FDA released warnings about the risk of blood clots leading to a boxed warning. All patients irrespective of their risk factors for developing thromboembolism should be monitored for signs and symptoms of pulmonary emboli. Sudden death in patients using high doses of tofacitinib was seen in patients primarily with rheumatoid arthritis and not with inflammatory bowel disease [16,17]. Another important concern related to the use of tofacitinib is the increased risk of lymphoma and nonmelanoma skin malignancies [18]. In a recent study, 1455 patients receiving tofacitinib at a dose of 5 mg twice daily and 1456 patients receiving tofacitinib at a dose of 10 mg twice daily were compared to 1451 patients receiving a TNF inhibitor. Over a 4 year follow up period, incidences of cancer and major cardiovascular events were higher in patients receiving the combined tofacitinib doses (4.2% and 3.4%, respectively) than with a TNF-alpha inhibitor (2.9% and 2.5%) [19]. The hazard ratios were 1.33 for major cardiovascular events and 1.48 for cancer (particularly non-melanoma skin cancer); the non-inferiority of tofacitinib was not demonstrated. Rarely, gastrointestinal perforations can occur during tofacitinib therapy with data demonstrating and incidence of 0.2% [20]. It is important to remember that patients should be advised to reduce their dose of tofacitinib in half when combining treatment with cytochrome P450 inhibitors such as fluconazole and ketoconazole.

Selective JAK inhibitors have also been recently studied for the treatment of patients with IBD, including Crohn’s disease. Filgotinib, is a selective JAK inhibitor that was approved by the FDA for the treatment of rheumatoid arthritis. Filgotinib selectively targets the JAK1 cytokine at a 30-fold selectivity over JAK2. JAK2 inhibition is thought to lead to higher rates of anemia and thrombocytopenia through the interfering of erythropoietin and thrombopoietin and granulocyte-macrophage colony-stimulating factor which would make selective JAK1 inhibition an attractive option [21,22]. The phase II Fitzroy study demonstrated early clinical benefit of filgotinib in patients with Crohn’s disease. Fitzroy included patients with a disease activity score (CDAI) of 220-450 and confirmed endoscopically active Crohn’s disease. A total of 174 patient with moderate-to-severe active Crohn’s disease were randomly assigned to receive 200 mg of filgotinib daily or placebo for 10 weeks. Clinical remission (indicated as a CDAI score of <150) at 10 weeks was achieved in 47% of patients treated with filgotinib and 23% of patients who were given placebo (P = 0.0077). Endoscopic improvement at 10 weeks was not significantly different [23]. The phase II study, Divergence 2, examined the effect of filgotinib in patients with perianal fistulizing Crohn’s disease. Patients with a documented history or perianal fistulizing Crohn’s disease with at least one to two external openings with drainage previously treated with immunomodulators or anti-TNFs were randomly assigned to receive filgotinib 200 mg, 100 mg or placebo once daily for 24 weeks. The primary endpoint was fistula response with a reduction of greater than 1 from baseline in the number of fistulas and no fluid collections seen on MRI at week 24. Unfortunately, the study was not well powered as there was low recruitment rates due to the COVID-19 pandemic leading to a total of 57 participants. Results did demonstrate a numerically higher proportion of patients in the filgotinib 200 mg group (47%) versus the placebo group (25%) who achieved the primary endpoint [24]. Further studies with a large patient population will be required to further elucidate the efficacy of filgotinib in patients with fistulizing Crohn’s disease.

The Selection trial included two induction studies, a maintenance study, and a long- term extension study examining the efficacy of filgotinib in the treatment of moderate-to-severe ulcerative colitis. Adults with moderate-to-severe ulcerative colitis were randomized to filgotinib 200 mg, 100 mg or placebo once daily for 11 weeks. Patients who responded to selected treatment at week 10 were re-randomized to continue filgotinib or placebo for an additional 47 weeks. Clinical remission was evaluated at week 10 and 58. Filgotinib demonstrated clinical remission rates significantly improved over placebo (47% vs 23%) at 10 weeks. Secondary endpoints such as endoscopic remission, mucosal healing, and deep remission did achieve numerical improvement but failed to achieve statistical significance. At week 58 remission was achieved at a rate of 58% in the filgotinib group compared to placebo at 29.5%. These findings suggest that filgotinib is efficacious at inducing and maintaining remission in patients with ulcerative colitis. Due to the efficacy demonstrated by filgotinib regulatory approval for use in moderate-to-severe ulcerative colitis as well as Crohn’s disease is expected soon. The common side effects reported in patients taking filgotinib are quite similar to tofacitinib including but not limited to serious infections, herpes zoster, venous thrombosis, pulmonary embolism and gastrointestinal perforations [25,26]. It is of note that filgotinib was rejected for approval by the FDA in the treatment of rheumatoid arthritis on concerns of toxicity and reduced sperm count [27,28]. Two ongoing trials (MANTA and MANTA-Ray) are pending and will provide additional safety data on the matter in patients with IBD.

Another highly selective JAK inhibitor that was approved by the FDA for use in patients with rheumatoid arthritis, psoriatic arthritis, and atopic dermatitis and also has been studied for its potential benefit in IBD patients is upadacitinib. This molecule is even more selective for JAK1 then filgotinib and has been investigated in the Celest phase 2 trial [29,30]. Patients with ulcerative colitis who had been previously exposed to anti-TNFs were evaluated after 16 weeks for primary endpoints of clinical remission, which included a patient reported outcome of stool frequency and abdominal pain score. In the induction phase of the study, although a numerical benefit in clinical remission could be observed in the group on twice daily 6 mg upadacitinib, it did not demonstrate a statistical response over placebo. The phase II study showed that the clinical remission and endoscopic improvement were achieved better than placebo as well as reduction in inflammatory markers. Phase III clinical trials of upadacitinib are ongoing and will hopefully shed more light on its efficacy and risk profile. Upadacitinib has similar adverse events as seen with tofacitinib including major adverse cardiovascular events and serious infections [31]. Due to the concerns of significant adverse events with tofacitinib, filgotinib, and upadacitinib, the development of a more gut selective pan-JAK inhibitor has been investigated. TD-1473 is a pan-JAK inhibitor that has demonstrated such a gut selective effect on mice with in-vitro studies [32]. A Phase 2b/3 set of clinical trials is currently ongoing to assess the efficacy and safety of induction and maintenance therapy with TD-1473 in subjects with moderate-to-severe active ulcerative colitis. Preliminary results were promising in endoscopic improvement along with reduction in fecal calprotectin and CRP levels with TD-1473 compared to placebo. If its further effectiveness can be demonstrated with this pending trial it has the potential to limit severe systemic side-effects caused by other non-GI selective JAK inhibitors. TYK2 is one of the JAK-STAT family proteins that is involved in intracellular cytokine signaling and inhibition of which blocks IL-12, IL-23 and IFN [33]. The oral TYK2/JAK1 inhibitor is well tolerated and more selective than other JAK inhibitors potentially limiting toxicity. Two oral TYK2/JAK1 inhibitors, deucravacitinib and brepocitinib, are currently recruiting in phase II clinical trials for the treatment of moderate-to-severe ulcerative colitis and also, Crohn’s disease.

Sphingosine-1-Phosphate Receptor Modulators

Sphingosine 1- phosphate (S1P) receptors are G protein coupled receptors (S1P1-S1P5) that regulate the response and function of various cellular and organ systems including cell migration, proliferation, immune response, and trafficking of T and B lymphocytes from lymphoid organs [34,35]. Their role in the ability of immune cells to migrate to inflamed tissues has made them a potential new target of inhibition for the management of IBD. Ozanimod is a new oral small molecule agent that binds with high affinity to several S1P receptor subtypes leading to internalization of the receptor in targeted lymphocytes and prevention of lymphocyte trafficking [36]. Ozanimod was approved for the treatment of the patients with relapsing multiple sclerosis in 2020 and then for patients with moderate-to-severe ulcerative colitis in 2021 by the FDA. Sandborn et al performed a phase III double blind and placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderate-to-severe ulcerative colitis [37]. Patients were assigned to receive oral ozanimod 1 mg or placebo once daily and patients in a second cohort received open label ozanimod. They found that clinical remission was significantly higher in patients who received ozanimod than those who were on placebo (37% vs 18.5%, P<0.001). Clinical response was also significantly higher in the ozanimod group (60% vs 41%, P<0.001). The investigators found that rates of serious infection were equal in both groups. A few patients on ozanimod had higher rates of elevated liver transaminases. Adverse events have been reported with ozanimod treatment including herpes zoster, bradycardia, and elevation of liver enzymes, atrioventricular conduction delays and macula edema. Ozanimod is also being studied for the treatment of Crohn’s disease. In the phase II Stepstone study involving 69 patients with Crohn’s disease, 39.1% of patients who received ozinamod had clinical remission at week 12. There was no incidence of bradycardia or arrhythmias in these patients [38]. Phase III, placebo-controlled induction and maintenance studies of ozanimod are currently recruiting for moderate-to-severe Crohn’s disease. Etrasimod is another oral S1P receptor subtype 1 modulator which has demonstrated potential efficacy in the treatment of patients with IBD. In the phase II Elevate trial involving 156 patients with ulcerative colitis, those patients receiving a 2 mg dose of etrasimod demonstrated endoscopic improvement over placebo (41.8% vs 17.8%, P=0.003). Also, compared to placebo, the etrasimod 2 mg group had a higher rates histologic remission (19.5% vs 6.1%; p=0.03). Etrasimod adverse events were reported as minimal with a small group of patients developing a transient, asymptomatic, low grade atrioventricular block that resolved spontaneously. Amiselimod is an oral S1P receptor modulator with higher selectivity for S1PR1 than other S1P receptor modulators [39]. A phase II trial with this agent is pending in patients with active Crohn’s disease.

Anti-Adhesion Molecules

Migration of proinflammatory T cells into the gut facilitates inflammation that is characteristic of IBD [40]. Anti-adhesion agents that block lymphocyte trafficking to the gut are being investigated in patients with IBD. A variety of oral small molecules including alfa-4 integrin antagonists have been studied. AJM300 is an oral small molecule agent that targets alfa-4 integrin. A phase II study in 102 patients with moderate-to-severe ulcerative colitis showed higher rates of clinical response (62.7% vs 25.5%, p=0.0002), clinical remission (23.5% vs 3.9%, p= 0.0099) and mucosal healing (58.8% vs 29.4%) [41]. No major adverse events were reported. A phase III trial is ongoing with AJM300 in patients with ulcerative colitis. There is extensive research of other anti-adhesion agents in the treatment of inflammatory bowel disease.

Phosphodiesterase 4 Inhibitors

Phosphodiesterase 4 (PDE4) is part of a group of enzymes that catalyze the breakdown of cyclic adenosine monophosphate (cAMP). In inflammatory cells, PDE4 is the dominant enzyme responsible for this reaction and the resulting decrease in cAMP levels leads to an increase expression of proinflammatory factors. Thus, it has been postulated that if PDE4 were inhibited the resulting increase in cAMP levels would lead to the decreased expression of a number of proinflammatory factors including TNF-alfa, IL- 17, IL-23, and up-regulates anti-inflammatory IL-10 [42]. This makes PDE4 a potential target for the treatment of inflammatory disorders. Apremilast is an oral small molecule PDE4 inhibitor which has been approved by the FDA for the treatment of adults with psoriatic arthritis, plaque psoriasis, and Behcet’s disease. A recent phase II clinical trial demonstrated the clinical effectiveness of apremilast in the treatment of moderate-to-severe ulcerative colitis. The investigators performed a double-blind, placebocontrolled trial in patients with active ulcerative colitis who were either biologic naïve or had failed conventional therapies. Patients were randomly assigned to apremilast 30 mg twice daily, 40 mg twice daily, or placebo for 12 weeks. After which patients were then randomly assigned to receive apremilast 30 mg or 40 mg twice daily for an additional 40 weeks. Endoscopies were performed and biopsies were obtained at the initial encounter, week 12, and week 52 after initiation of the study. The primary endpoint for the study was clinical remission at week 12 (a Mayo score of 2 or less). The investigators found that clinical remission was achieved in the 30 mg apremilast group at a rate of 31.6% versus 12.1% of patients in the placebo group (P = 0.01) [43]. Both apremilast groups (the 30 mg and 40 mg groups) had similar improvement from baseline in Mayo score components. At week 52 clinical remission was achieved by 40.4% of patients. Endoscopic healing was achieved in 41.4% of patients in placebo compared to 73.7% in the 30 mg group (p< 0.0001). Moreover, both the 30 mg and 40 mg apremilast groups showed greater reduction in serum C-reactive protein and fecal calprotectin compared to placebo. In terms of safety, headache and nausea were found to be the most common side effect. One patient had an episode of acute pancreatitis but this was no attributed to the study drug. Currently, a phase III trial has not been registered for patients of ulcerative colitis or Crohn’s disease.

Anti-Tumor Necrosis Factor Agents

Anti-TNF agents were the first class of biologic medications approved for the treatment of patients with inflammatory bowel disease [44]. Limitations of this class of medications includes the intravenous or subcutaneous administration, infusion reactions, systemic side effects related to immunosuppression, and high cost [45]. An oral agent with a mechanism of action restricted to the gastrointestinal tract would be helpful to overcome some of these challenges of parenterally administered anti-TNF agents. AVX- 470 is an oral polyclonal immunoglobulin that inhibits TNF-alpha locally in the gastrointestinal tract, minimizing systemic exposure [46]. In a double blind, placebo-controlled trial, 37 patients with active ulcerative colitis received AVX-470 (0.2, 1.6, or 3.5 grams per day) or placebo for 4 weeks. Endoscopic activity was assessed pre and post treatment exposure.46 At all AVX-470 doses, 25.9% of patients achieved clinical response compared with 11.1% of those in the placebo group. Both groups were found to have similar adverse event rates without significant infectious reported.46 Further clinical trials evaluating the efficacy of AVX-470 are ongoing [47,48]. OPRX-106 is another oral anti-TNF agent which is currently undergoing evaluation for its efficacy in the treatment of inflammatory bowel disease [49]. In a phase II randomized open label clinical trial, 25 patients with ulcerative colitis who were administered OPRX-106 demonstrated clinical remission and mucosal healing with no major adverse events including immunogenicity. Initial studies with oral anti-TNF agents have shown promising results with the potential for enhanced safety and decreased immunogenicity. However, larger trials are needed to evaluate efficacy, safety and cost effectiveness.

Conclusion

Despite tremendous advancements in the field of treatments for IBD, there are significant rates of primary non-response, loss of response, adverse events and high cost thereby necessitating additional treatment options. Fortunately, the rapidly growing number of oral small molecule targeted therapies offers ease of administration with durable effectiveness, and an improved safety profile compared to the currently approved therapeutic agents.

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Lupine Publishers|Molecular detection of aflatoxin producing Aspergillus species isolates in some chicken meat cuts in Gharbiya governorate, Egypt

Abstract

Contamination with fungi and their toxins is considered one of the most dangerous hidden pollutants that threaten the health of the consumer. The presence of mycotoxins in various foods has been recorded, despite their apparent safety for human consumption. Therefore, the current study was conducted to evaluate the prevalence of Aspergillus species by culture method; and aflatoxinproducing genes molecularly in total of 75 random samples of chicken cuts represented by wing, breast and thigh (25 of each) that were collected from various groceries and poultries shops located at Gharbiya governorate, Egypt. Results of culture and isolation techniques revealed detection of Aspergillus sp. in 36, 48 and 44% of the examined wing, breast and thigh samples, respectively. Moreover, microbiological identification of the isolated strains showed presence of A. niger, A. flavus, A. fumigatus, A. terreus and A. parasiticus in 16, 13.3, 10.6, 1.3 and 1.3% of the total population of the examined samples. Molecular detection of some aflatoxin production regulating genes (OmtA, Nor1 and Ver1) in ten Aspergillus sp. isolates revealed their detection in 8/10 (80%), 8/10 (80%) and 7/10 (70%) represented by positive bands at molecular weight of 1024, 400 and 537 bp, respectively. Referring to the recorded results, chicken cuts may possess a great silent hazard to the human being under improper good manufacturing practices and inadequate hygienic conditions during handling and storage.

Introduction

Chicken meat and meat products production in developing countries plays an essential role in supporting food security and poultry meat demands Wong et al. [1]. Contamination of meat products with molds can be occur during different preparation stages during slaughtering under bad hygienic conditions using contaminated water or by adding contaminated spices with mold spores or during packing, handling, transportation and storage Khalalfalla et al. [2]. Contamination of meat with Aspergillus species, especially Flavi section, is one of the most hazardous microbial contamination as the majority of Aspergillus species are able to aflatoxins production that can cause diseases associated with aflatoxin poisoning and carcinogenic effects Leggieri et al. [3]. Acute aflatoxin poisoning may lead to death as was recorded in Kenya in 2004 Probst et al. [4], while chronic poisoning may lead to various recorded mutagens and cancers Benkerroum [5]. Aspergillus sp. was classified into two groups depending on their toxigenic impacts on food and human health; 1st group includes the aflatoxigenic species such as A. flavus and A. parasiticus, while the 2nd group contains the non-aflatoxin-producing species such as A. tamarii and A. oryzae Frisvad et al. [6]. Molecular analyses have been used to confirm aflatoxin productivity of Aspergillus species isolates. omtA, nor1 and ver1 genes are from the commonly used genes encoded aflP, aflD and aflM toxins detection in food items Sohrabi and Taghizadeh [7] yield an accurate, rapid and reliable records of toxigenic aspergillus species especially in food chain Sadhasivam et al. [8]. Therefore, the main target of the current study was to investigate the presence of toxigenic aspergillus species in some chicken meat cuts collected from Gharbiya Governorate markets, Egypt.

Material and Methods

Collection of samples : A total of seventy-five random samples of raw chilled chicken wing, chicken thigh, chicken breast (25 of each) was collected from different local poultries shops and different supermarkets at Gharbia governorate, Egypt. Samples were taken aseptically in polyethylene bags and were transferred to the laboratory in ice box for mycological examination. Preparation of samples (ISO [9]): Twenty-five grams from each sample were carefully and aseptically homogenized in blinder after mixing with 225 ml of sterile peptone water 0.1% to form a dilution of 1:10, from which tenth fold serial dilutions were prepared.

Determination of Aspergillus species

Culture of the prepared samples was performed according to ISO [10], where 0.1ml of the previously prepared serial dilutions was spreaded by mean of sterile L-shape glass rod over two Petridishes contained solidified Dichloran Rose Bengal agar with chloramphenicol (DRBC) then were incubated at upright position at 25Oc for 5 -7 days. Identification of isolated strains was performed according to Pitt and Hocking [11] macroscopically and microscopically as recorded in Table 1. Molecular detection of some aflatoxin producing genes of some isolated Aspergillus strains by cPCR

Oligonucleotide primers used in cPCR

Three pairs of omtA, nor1 and ver1 primers were prepared and collected from Metabion (Germany). Their special sequence and amplify certain products as were be displayed in Table 2.

Mycological DNA was extracted following QIAamp DNeasy Plant Mini kit Catalogue no. 69104. Preparation of master mix and thermal profile was adapted according to the manufacturer instructions (Emerald Amp GT PCR mastermix (Takara) Code No. RR310A).

Results

As recorded in Table 3, Aspergillus sp. was detected in 32(42.6%) of the total examined samples. In detail, breast samples recorded the highest contamination level (48%); followed by thigh and wing samples, respectively. Regarding with the genus identification, A. niger had the highest detection levels (16%) in the examined samples (Table 4). Referring to the obtained results of molecular detection of some aflatoxin producing genes as recorded in (Table 5) and (Figures 1-3); omtA, nor1 and ver1 genes were detected in 8/10 (80%), 8/10 (80%) and 7/10 (70%) of the examined A. flavus isolates, respectively. presence of these genes indicated the producibility of the examined strain for aflatoxins P, D and M, respectively.

Discussion

Chicken meat and meat products comply an important source of human protein supplement all over the world because they provide good source of digestible protein, low cholesterol fat, essential amino acids, minerals, and different types of vitamins and minerals. In Egypt, as well as human population increasing, demand of animal proteins also is increasing represents a serious challenge in which poultry industry plays an essential role in filling nutrition gap as a rapid and more economic source of proteins (Shaltout et al. [12]). Mold contamination of meat and meat products have been considered a serious source of food spoilage resulting in different organoleptic changes in flavor, color, texture, odor referred mainly to the fungal deterioration especially in poor developing countries due to lack of hygienic measures during processing and handling (Lorenzo et al. [7]). Presence of mold in foods may be referred to the rapid, easy disperse and wide spread of the fungal spores which are abundant in the environment introducing food chain through dust, water, workers and equipment. Their presence in food samples is a serious public health concern as these fungi may be associated with the production of mycotoxins (Benedict et al. [13]). Aspergillus species represents an important mycotic infection in public health concern as a human pathogen and as toxin-producing food contaminant. It releases a lot of spores which found in air, water, soil, plant debris, manure and animal feed. As fungal spore’s growing, it secretes digestive enzyme and mycotoxins leading to food spoilage and human mycotoxicosis (Richardson and Rautemaa-Richardson [14]). Referring to the recorded results in Table 3, Aspergillus sp. was prominently detected in breast samples other than wings and thighs samples, which came in agree with the previously recorded results of Darwish et al. [15] and Shaltout et al. [16] who found that the examined breast samples were more contaminated with fungal infection than wing and thigh samples. While the current prevalence of aspergillus species in the examined samples came lower than those recorded by Hassan [17] who found Aspergillus sp. in all the examined samples (100%) collected from Gharbiya governorate, Egypt. Moreover, Abuzaid et al. [18] also detected A. flavus and A. niger in 40 and 80% of the examined sausage samples of chicken origin, respectively. Referring to the obtained results of the microbiological identification of Aspergillus sp. isolates as recorded in Table 4, they came in agree with the previously reported results by Darwish et al. [15] who found that A. niger was the predominant detected strain, followed by A. flavus and A. parasiticus in the examined samples of chicken cuts collected from Zagazig city, Egypt. Some mold species can cause respiratory infections representing a significant risk for individual with severely weakened immune system (OSHA [19]). Presence of mold in high incidence indicate bad hygienic measures adopted during handling, preparation and processing El Abbasy [20]. Mycotoxins have been defined as naturally occurring secondary fungal metabolites produced in meat and meat products by direct growth of toxigenic molds such as Aspergillus species which produce Aflatoxins and Ochratoxins which threat public health due to their carcinogenic, hepatotoxic, nephrotoxic, teratogenic and mutagenic effects in human and animals Agriopoulou et al. [21]. Aflatoxins are produced by a polyketide pathway that pass through about twenty-seven enzymatic reactions which have been regulated by sets of genes including nor-1, ver-1 and omtA have been shown to be involved in this process. aflD (nor-1) encodes a norsolorinic acid ketoreductase needed for the conversion of the 10-keto group of Norsolorinic Acid (NOR) to the 10-hydroxyl group of Versicolorin A (VERA) Zhou and Linz [22]. aflM (ver-1), predicted to encode a ketoreductase, is involved in the conversion of VERA into Sterigmatocystin (ST) Henry and Townsend [23]; aflP (omtA) codes for O-methyltransferase, which is one of the main genes responsible for transforming ST into O-methylsterigmatocystin (OMST) that is the precursor for aflatoxin production Yabe et al. [24]. Many other previous studies recorded detection of these genes in their Aspergillus isolates of food origin by various PCR techniques; Manonmani et al. [25], Rodrigues et al. [26], and Hassan et al. [27], who conducted several studies investigating the aflatoxigenicity of Aspergillus sp., could detect different genes in their Aspergillus isolates [28,29].

Conclusion

It could be concluded that, breast samples revealed the highest contamination levels with Aspergillus sp.; in addition, A. niger was the prominently detected strain. PCR technique is a unique diagnostic tool for detection and identification of aflatoxigenic Aspergillus strains especially if the field of food safety. So, application of strict hygienic measures, proper use of water supply and food additives from good sources is recommended.

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lupine publishers|CT Manifestation of Abscess Occupying the Infratemporal Fossa and Temporoparietal Region in a 73-Year-Old Male- Case Report

Abstract

Commonly available dental care and a widespread use of antibiotics in an outpatient setting have not eliminated odontogenic infections which may require inpatient admission as potentially life-threatening conditions. The spread of infection to the deep fascia of the head and neck may lead to severe and life-threatening complications, such as airway obstruction, mediastinitis, sepsis and septic shock, endocarditis or intracranial abscess formation. Clinical presentation of deep fasciitis of the head and neck may not correspond to the systemic deterioration in the same patient. Therefore, contrast-enhanced computed tomography should be a standard diagnostic imaging in such cases, as it enables accurate location of inflammation, whereas contrast enhancement enables differentiation between soft tissue inflammation and fluid collections based on their density relative to the one of air. It substantially aides the diagnosis, where the history and clinical presentation are inconclusive. The aim of the paper is to discuss the diagnostic management, presentation and spread of odontogenic infections of the head and neck by presenting the rare case of abscess occupying the left infratemporal fossa and temporoparietal region in a 73-year-old male.

Keywords: Craniofacial Ct; Odontogenic abscess; Odontogenic infection; Temporal fossa abscess; Phlegmon of the face; Surgical treatment

Introduction

General characteristics of head and neck infections

The head and neck infections have their distinct characteristics which differ them from the infections affecting other anatomical locations. It is primarily associated with a complex craniofacial and cervical anatomy, the presence of teeth in the oral cavity, the proximity of paranasal sinuses, abundant blood supply and the presence of vital sensory organs (visual, auditory and olfactory senses) [1,2]. Inflammation develops as a bodily defense mechanism against a noxious agent, which can be either a physical or a biological (e.g. pathogens). The bacterial infection develops as the host immune barrier becomes compromised. This is the key mechanism responsible for head and neck inflammation and infection. Pulp necrosis, periapical periodontitis with abscess formation, infected dental cysts as well as infectious complications of partially or completely impacted teeth are the main source of pathogens in head and neck infections [3,4]. Necrotised pulp of mandibular and maxillary molars, premolars and, less often, single root teeth is the most common site of origin [5-7]. Periodontitis is the aetiologic factor in 20-30% of odontogenic infections [8-10]. The second group of aetiologic factors in head and neck infections are non-odontogenic conditions, including sialadenitis, sinusitis, lymph node abnormalities, and skin infections, such as furunculus (boil). The inflammation can manifest clinically as inflammatory infiltration, abscess and the most severe form of infection, that is, phlegmon of the head and neck. Odontogenic infections are mostly cause by mixed bacterial flora. The most commonly cultured isolates include Streptococcus viridans and Klebsiella pneumoniae [10,11]. As the infection progresses, anaerobic bacteria emerge, which is associated with decreased oxyreductive potential and pH reduction in affected tissues [12-14]. Synthetic penicillin remains the drugs of choice in odontogenic infections of the head and neck, mainly due to its high efficacy, minimum side effects, easy availability and low cost. Second generation cephalosporins, belonging to the class of -lactam antibiotics, are used qually often. The main representative of this drug category is cefuroxime, which has a very broad spectrum, good penetration to the bone tissue, which is vital in treatment of odontogenic infections. It is administered parenterally in its leading pharmaceutical form in an inpatient setting. If anaerobic strain involvement is suspected, metronidazole is a treatment of choice [15-17]. The indications for antibiotic therapy include severe systemic symptoms, extensive local inflammation, immunosuppression, systemic comorbidities (diabetes, RA, liver damage) and upper face or mid-face involvement. Empirical, often combined, treatment should be started immediately and adjusted once the susceptibility testing report is available (usually 72 hours). Cultures and antimicrobial susceptibility testing aim at identifying the causal pathogens, their susceptibility to different antibiotic classes and determining the minimum inhibitory concentration (MIC) needed to inhibit the pathogen growth. The MIC is helpful for determining the effective dosage [18].

Infection spread within the head and neck

Spread of head and neck infections may occur in a contiguous fashion, along planes of least resistance from the supporting structures of the affected tooth to fascial spaces of the head and neck.Having crossed the strongest barrier of cortical bone and periosteum, the infection spreads along the adjacent soft tissues [18,19]. The crucial factors which determine the spread of infection include its site of origin (maxilla, mandible), anatomical relationship between the site of origin and muscle insertions/ ligaments, alongside the detailed anatomy of craniofacial and cervical fascial layers, spaces and fossae. The fascial space is referred to as the anatomical fascia-lined space, which contains loose connective tissue and additional structures. The fascia is a compact connective tissue membrane, which covers muscles, muscle groups and ensures structural integrity of the body. Its function is complex with protection and regeneration of tissue it surrounds as the key role. A thorough knowledge of the anatomy is essential to understand the passageway of infection and associated clinical signs and symptoms [20,21].

Case description

A 73-year old man presented as an emergency at the Department of Maxillofacial Surgery in Wrocław due to moderately increasing oedema of the left temporal region. He had a history of dental extraction of gangreneous roots of tooth 27 two weeks earlier under local anaesthesia, as well as chronic, treated, hypertension. He reported that 3 days following his extraction, the oedema developed “near his left ear”, which subsequently enlarged yet remained fairly asymptomatic. He did not present with any systemic symptoms such as fever, chills or malaise. The patient reported that he saw his GP about it twice, who recommended cold compresses and non-steroidal anti-inflammatory drugs (NSAIDs). Due to the problems with dental visit, GP issued a referral to hospital treatment to Maxillofacial Department. Clinically, intraoral examination revealed severe dental caries, roots of teeth 13, 23, 32, 42, 46 eligible for extraction and clinically healed dental alveolus of tooth 27 with no signs of inflammation within the left maxilla. An extraoral examination revealed significant head asymmetry. There was a massive oedema stretching from the left subtemporal space, through to the temporal and parietal region (Figures 1a-1c). The oedematous area was medium-soft, fluctuant and slightly tender upon palpation. There was no history of head or craniofacial injury. The patient was verbally responsive and oriented, in a good general condition, with no signs of fever or malaise. He was admitted to the Department of Maxillofacial Surgery as an inpatient for further diagnostic assessments and treatment.

Figure 1a:Patient’s head and neck - an “en face” view.

Figure 1b: Patient’s head and neck – a left profile view.

Figure 1c: Patient’s head and neck – a right profile view.

His vital signs at admission were: temperature 36.4 C, blood pressure 140/80 and HR 100’. The patient reported using the following medications: trimetazidine MR 35mg (once a day each morning), atorvastatin 20mg (once a day each morning), ramipril 10mg (twice a day), aspirin 75mg (once a day at bedtime), and bisoprolol 5mg (once a day at bedtime). The WBC count was normal (7.34*10^3/uL, reference range 4-10*10^3/uL), but the C-reactive protein level was elevated (CRP 34.40mg/L, reference range 0-5mg/L). The contrast-enhanced CT of the head was performed immediately. The reported abnormalities included “an irregular area of oedema and inflammatory infiltration within the left masticator space and within the left subtemporal fossa with abscess formation, irregular in outline, sized 2.5 x 8.0cm and small gas collections (…). An extensive abscess and soft tissue phlegmon are present within the cranial integuments, in the left temporoparietal area. The abscess contains gas collections, is 2.7cm thick and 12cm wide (…).

Figure 2: CT image of frontal sinuses plane.

The submandibular lymph nodes and lymph nodes against the carotid vessels on the left are fairly small.” The figures below present contrast-enhanced axial computed tomograms of the head and neck (Figures 2-4) and coronal (frontal) image reconstructions (Figures 5-7). In the light of the above findings, empirical intravenous antibiotic therapy was started, including biocefuroxim 1.5g every 8h, metronidazole 500mg every 8h, fluid replacement therapy (Ringer fluid 1000ml/24h) and pain management. The surgical intervention was performed right after CT scans evaluation and antibiotic deliviery. Under a general anaesthesia and orotracheal intubation, the two-step procedure was performed. The first step involved a comprehensive dental treatment-extraction of potencial inflammatory foci in oral cavity, and the second one - abscess incision and drainage. Having disinfected the skin in the left temporal area, fresh sterile drapes were put in place and the reported purulent fluid collections were incised and drained. Following a manual revision of abscess cavity recesses, a sample for microbial cultures was taken and drains were sutured in place (Figures 8,9). On subsequent days, the patient’s condition improved with decreasing amount of drained contents. On day 3. (72hrs), a negative culture for aerobic bacteria was obtained, followed by a positive culture for anaerobic bacteria on day 6. Gemella Morbillorum was isolated, resistant to metronidazole and susceptible to amoxicillin and clindamycin. Gemella morbillorum is Gram-positive, facultatively anaerobic and non-spore forming coccus. G. morbillorum liveas as a commensal organism of the mucous membranes of the human oropharynx, gastrointerstinal and female genital tracts [21].

Figure 3: CT image of orbits plane.

Figure 4: CT image of maxillary sinuses and subtemporal fossa plane.

Figure 5: CT image (frontal plane) of the orbital apices.

Figure 6: CT image (frontal plane) of the external auditory meatuses.

Figure 7: CT image (frontal plane) of the deep cervical muscles.

Figure 8: Intraoperative view - an incision in the left temporal area with posing purulent discharge.

Figure 9:Intraoperative view after the incision and drainage with drains protruding from the abscess cavity.

The antibiotic treatment was adjusted accordingly replacing metronidazole with clindamycin 600 mg every 12 hrs and leaving biocefuroxim dosage unchanged. The decision was guided by susceptibility test findings and the fact that clindamycin itself has fairly low efficacy against Gram-negative aerobic bacteria [17]. The laboratory tests were repeated 5 days later, with a CRP reduction to 13.37mg/L. One day later, the follow-up contrast-enhanced CT of the head and neck was performed (Figures 10,11). The report stated that “the previously reported extensive inflammatory infiltration and soft tissue abscess within the left craniofacial area was incised and drained, subsequently reducing in size (…). The inflammatory lesions within the temporal and subtemportal fossa as well as within the masticator space have also slightly decreased in size”. The patient was hospitalised for 18 days. One day prior to scheduled discharge, the drains were removed and laboratory tests repeated. The findings included CRP reduction to 4.91mg/L [reference range 0-5.0mg/L] and almost completely resolved oedema. The patient was discharged home with continued course of antibiotics (clincamycin 600 mg PO twice a day), wound cleaning and dressing change instructions and a follow-up appointment at the Maxillofacial Clinic booked in 7 days.

Figure 10: Control CT image (frontal plane) of the orbital apices.

Figure 11: Control CT image (frontal plane) of the external auditory meatuses.

Discussion

Odontogenic infections still constitute a major group of head and neck infections [2-4]. An infection presenting as local infiltration or abscess may develop secondarily to pathogenic flora presence in necrotic pulp or after any intraoral/ dental procedures involving the alveolar process. The most common procedure is dental extraction, which is always associated with bacteriemia. With local and/or systemic vulnerability and risk factors, dental extraction may lead to a local or-very rarely-systemic infection. The treatment of choice in abscesses is a surgical intervention including incision and drainage, in some cases accompanied by medical treatment [6,8,11]. The decision of inpatient admission can be very challenging at times. It should be informed by a thorough history, clinical assessment and diagnostic imaging [12,20]. Any potential life-threatening conditions associated with dyspnoea warrant inpatient admission. Similarly, intraoral abscesses, including canine fossa abscesses, should be treated surgically under general anaesthesia. The infection spread in this case via the route typical of maxillary molars, along the subtemporal space, extending through the temporal space, up to the parietal area [10-13]. Effective treatment of odontogenic infections of the head and neck requires accurate diagnosis. It should be noted that the severity of the general condition may not correspond to the clinical presentation, especially with the involvement of parapharyngeal or pterygomandibular spaces [9,13,20]. Contrastenhanced computed tomography is a diagnostic imaging modality of choice in extensive infections of the head and neck, as it enables precise location of the inflammation, especially with the infection spread to the deep fascia of the head and neck. Contrast-enhanced computed tomography helps to differentiate between the nature of the condition (inflammatory infiltration, abscess, phlegmon) and precisely determines its location, identifying the surgical target [1,16,13]. The abscess occupying the infratemporal, temporal and parietal fossae may also be occurred by trauma or laryngological causes. However odontogenic infections constitiute over 49% in head and neck region [1,14,16].

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lupine publishers|CT Manifestation of Abscess Occupying the Infratemporal Fossa and Temporoparietal Region in a 73-Year-Old Male- Case Report

Abstract

Keywords: Craniofacial Ct; Odontogenic abscess; Odontogenic infection; Temporal fossa abscess; Phlegmon of the face; Surgical treatment

Introduction

General characteristics of head and neck infections

Infection spread within the head and neck

Case description

Discussion

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Lupine Publishers|Radiology; USG and Colour Doppler of Post Renal Transplant Complications

Abstract

Kidney transplant is the treatment of choice for patients with end-stage renal disease. Kidney transplant offers better quality of life. It is more cost effective than hemodialysis. Advances in surgical technique, along with improvement in organ preservation and immunosuppression have improved patient outcomes. Post-operative complications, however, can limit this success. Ultrasound and Doppler study is the primary imaging modality for evaluation of renal transplant, providing real –time information about complication in graft. A multimodality approach including CT scan, MRI or conventional angiography may be necessary in cases when sonography and Doppler are inconclusive to diagnose the etiologies of these complications. Radiologists play an integral role within the multidisciplinary team in care of transplant patient at every stage of the transplant process. Therefore, the radiologist should always be aware when evaluating the failing renal graft, whether the cause is renal or extrinsic. In this pictorial essay we tried to gather the most common complication of transplant kidney in different cases that occurred in our hospital, with an emphasis on Ultrasound and Doppler study.

Keywords: USG; Colour Doppler; Post renal transplantation; Complications

Introduction

The preferred modality for renal replacement is renal transplantation, and its superiority in prolonging the longevity of patients with end-stage renal disease is well established [1]. Kidney transplantation is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantation depending on the source of the donor organ. Due to improvement in transplantation technology, advancement in immunosuppressant and graft preservation techniques the 1-year survival rates for grafts, are reported to be 80% for mismatched cadaveric renal grafts; 90% for nonidentical living related grafts; 95% for human lymphocyte antigen-identical grafts [2]. Radiologists play a major role at every stage of the transplant process with transplantation team. Ultrasonography with colour Doppler is the principal modality used for evaluation of renal allograft. USG is a relatively cheap, noninvasive, and non-nephrotoxic modality. It is applied for diagnostic and monitoring purposes in the post-transplant period. This pictorial essay describes USG and Doppler imaging appearances of the major complications that may occur in renal transplantation. All our images have been obtained from a single our center which is major transplantation center in India. All post renal transplant patients undergo a USG and comprehensive Doppler evaluation on post-operative day one. The sonographic examination algorithm includes gray-scale evaluation of the graft and spectral Doppler. Further imaging is based on clinical follow-up including daily monitoring of laboratory values. If clinical parameters are abnormal, repeat sonography is performed and depending on the results, CT, MRI, or angiography may be requested.

Surgical Technique

Surgical technique and location of placement of renal allograft depends on the variation in arterial and venous anatomy of donor. The transplanted kidney is usually placed extraperitoneally in the patient’s right iliac fossa (less commonly in left iliac fossa), with end-to-side or end to end anastomosis to the external iliac vasculature. The currently preferred method for restoring urinary drainage is ureteroneocystostomy, a procedure by which the ureter is implanted directly into the dome of the bladder (Figure 1).

Figure 1: Diagrammatic representation of anatomical and anastomotic arrangement (end to side fashion) in renal transplantation in right renal fossa

Post renal transplantation complications

Urologic Complications

The prevalence of urologic complications varied from 10% to 25% with a mortality rate ranging from 20% to 30%. Incidence rate is decreased range between 3% and 9% in the current era because of advancement in surgical techniques and frequent use of ureteral stents [3,4].

Urinary Obstruction

a) Incidence: 2%-5% of kidney transplant recipients. b) Site of obstruction: Approx. 90% of stenoses occur in the distal third of the ureter due to its poor vascular supply. c) Imaging appearance: US can easily confirm the diagnosis of hydronephrosis and dilated renal pelvis and thus determine the level of ureteral obstruction (Figure 2). When contents of pelvic calyceal system are echogenic and weakly shadowing, fungus balls should be considered, whereas low-level echoes suggest pyonephrosis (Figure 3).

Figure 2: Grey scale USG image shows (A) dilated pelvic calyceal system, (B) dilated ureter may favors urinary obstruction.

Figure 3: Grey scale USG image shows echogenic material within (A) dilated pelvic calyceal system, (B) dilated renal pelvis may favors debris.

Urine Leaks and Urinomas

a) Incidence: up to 6 % of renal transplant recipients [5] b) Location: extraperitoneal or intraperitoneal, if intraperitoneal may present with ascites. c) Imaging appearance: USG findings are nonspecific, well defined anechoic fluid collection with septa or without septation, adjacent to the lower pole of the transplant in most of the cases (Figure 4).

Figure 4: Grey scale USG image shows anechoic collection (A) near urinary bladder, (B) near lower pole of transplanted kidney may favors urinoma.

Drainage of fluid under ultrasound guidance and testing the fluid for creatinine helps to differentiate it from seromas or lymphoceles. High concentration of creatinine will be found in case of urinoma if we compare with serous fluid.

Calculous Disease

a) Incidence: 1% to 2 % of post-transplant cases develops clinically relevant stones as compared to general population [6]. As the kidney is denervated patient will not suffer typical renal colic. b) Imaging appearance: Calculus appears as strongly reactive focus of variable size producing acoustic shadowing on USG and twinkling artifact on colour Doppler (Figure 5). Other rare urologic complications are ureteric necrosis and vesico-ureteric reflux.

Figure 5: Grey scale USG image of transplanted kidney show echogenic focus with acoustic shadowing (A) in lower calyceal system, (B) in upper calyceal system, (D) in mid part of transplanted ureter and (C) with twinkling artifact on colour Doppler favoring calculus.

Peritransplant Fluid Collections

Fluid collection in peritransplant region has been reported in up to 50 % of renal transplantation. They are urinomas, hematomas, lymphocele and abscess, the clinical relevance of these collection is largely determined by their size, location and possible growth. In immediate postoperative period, small hematomas or seroma are almost expected. Their size should be documented at baseline examination. Rarely do they lead to graft dysfunction or obstruction of collecting system. Urinomas and hematomas are most likely to develop immediately after transplantation, whereas lymphoceles generally develop after 4 to 8 weeks. The ultrasonography characteristics of peritransplant fluid collections, however, are entirely nonspecific, correlation with clinical findings helps to restrict differential diagnosis. Ultimately, diagnosis may be made only with percutaneous aspiration and then biochemical analysis. Differentiation between Peritransplant and subcapsular collection is important. A subcapsular collection likely to cause mass effect on parenchyma, usually cresenteric and show extension along the contour of kidney deep to the renal capsule

Hematoma

a. Incidence: Varies from 4 to 8 % [7] b. Imaging appearance: Hematomas have a complex appearance. Hematomas appears echogenic in acute case and progressively become less echogenic with time (Figure 6). Chronic hematomas even appear anechoic, more closely resembling fluid and septation may develop later on.

Figure 6: Grey scale USG image shows echogenic collection in (A) at subcapsular region, (B) in peritransplant region favoring hematoma.

Lymphocele

a. Incidence: Affecting up to 20% of the patients [8] It occurs after surgery owing to the surgical disruption of the normal lymphatic channels along the iliac vessels or around the hilum of the graft. b. Imaging appearance: on Ultrasound it appears as anechoic bur may contain septation. They may become infected and gave more complex appearance (Figure 7).

Peritransplant abscesses

a) Imaging appearance: USG cannot always differentiate an abscess from other collection. Collection may show low level echoes and thick irregular wall. If gas is seen, an abscess is probable. In any pyrexia patient, any perinephric collection should be considered infected until proven otherwise through the appropriate imaging and guided diagnostic aspiration.

Figure 7: Grey scale USG image showing septated collection (A) near lower pole of transplanted kidney, (B) causing compression over renal pelvis and resulting in obstructive changes in transplanted kidney favoring lymphocele.

Parenchymal Complication / Graft Dysfunction

Diseases of the renal parenchyma are usually diffuse and often leads graft dysfunction. Differential diagnosis is difficult by imaging alone. USG is not sensitive or specific for evaluation; differential will be relying on biopsy. USG still has a central role in qualitative assessment of graft perfusion and to guide the biopsy.

Acute tubular necrosis (ATN)

Acute tubular necrosis is due to reversible ischemic damage to the renal tubular cells prior to engrafting and reperfusion injury. i. Incidence: affects 20–60 % of cadaveric renal grafts. ii. Time of onset: in the first 48 hours after transplantation. iii. Imaging appearance: No specific imaging pattern for the diagnosis of ATN. The kidney may appear normal, in severe cases it looks enlarged, edematous and echo poor with loss of corticomedullary differentiation (Figure 8) and shows elevated RI (above 0.8).

Figure 8: Grey scale USG image showing edema to us transplanted kidney with prominent pyramids and decreased cortical echogenicity may favors changes of Acute tubular Necrosis (ATN) or Acute Rejection (AR).

Rejection

Rejection can be classified according to the period of appearance as hyper acute (occurring within minutes), acute (occurring within days to weeks), late acute (occurring after 3 months), or chronic (occurring months to years after transplantation). Classification of renal allograft rejection by Banff classification of allograft pathology is routinely followed nowadays. It is based on a combination of histopathologic features coupled with molecular, serologic, and clinical parameters.

Acute Rejection (AR)

i. Incidence: up to 40% of patients in the early transplant period [9].

Figure 9: (A) Grey scale USG image shows enlargement of transplanted kidney, swelling of the medullary pyramids and echogenic sinus fat, (B) Spectral Doppler analysis shows elevated RI may favors changes of Acute Rejection (AR) or Acute Tubular Necrosis (ATN).

ii. Imaging appearance: Graft enlargement due to edema, Decreased cortical echogenicity, swelling of the medullary pyramids, echogenic sinus fat, edematous wall of pelvic calyceal system, focal hypoechoic areas in parenchyma which may favors infarct and collection in perigraft region due to necrosis or hemorrhage. PI and RI elevated in both ATN as well as in AR, but AR has high values of it. In severe cases, Power Doppler shows reduced, absent or reversed diastolic flow with elevation of the RI (Figure 9).

Chronic Rejection

Chronic rejection occurs in case of insufficient immunosuppression given to recipient to control the residual antigraft lymphocytes and antibodies. i. Imaging appearance: US appearance is not typical, ranging from normal to hyper echogenic, along with cortical thinning, reduced number of intrarenal vessels, and mild hydronephrosis (Figure 10). RI measurements are not reliable for this diagnosis. The diagnosis is made histologically.

Figure 10: (A) Grey scale USG image shows echogenic transplanted kidney with cortical thinning and minimal hydronephrosis, (B) Spectral Doppler image shows reduced diastolic flow and elevated RI may favors Chronic Rejection.

Drug Nephrotoxicity

Calcineurin inhibitors are key immunosuppression agents administered to avoid acute rejection, but they are nephrotoxic. A. Imaging appearance: USG may show completely normal results or nonspecific findings such as graft swelling, increased or decreased renal echogenicity and loss of cortico-medullary differentiation. Doppler study may show a RI increase of 0.80. Findings of USG and Doppler study should be correlated with the serum drug levels. USG and Doppler findings of ATN and AR is almost similar, but both can be differentiated by time course of the findings. Clinical & biochemical correlation and serial measurements of RI and Pulsatile index (PI) would be further helpful to monitor the patient.

Infections and abscesses

Incidence and time of onset: More than 80% of renal transplant recipients have at least 1 episode of infection during the first year of post transplantation.

Figure 11: Grey scale USG image shows ill-defined hypoechoic lesion (A) in mid pole, (B) in upper pole of transplanted kidney posteriorly Suggestive of Abscess formation. First one is proved case of fugal etiology and second one is pyogenic abscess.

I. Imaging appearance: USG appearance is quite variable. Focal pyelonephritis appear as a focal hyperechoic or hypoechoic area, but this finding is nonspecific because it can represent infarction or rejection also (Figure 11). Abscess has varied appearance on USG like- heterogeneous, hypoechoic or cystic. Urothelial thickening may be seen. In febrile post renal transplant patient low level echoes in dilated collecting system may favors pyonephrosis. Fungus ball appears as focal rounded, weakly shadowing or echogenic structure in dilated pelvic calyceal system. In emphysematous pyelonephritis, gas in the parenchyma of the renal graft produces an echogenic line with distal reverberation artifacts. Papillary necrosis has no typical sonographic findings, and it subsequently leads to ureteric obstruction.

End stage disease

Nonfunctional renal grafts are left in place in abdominal cavity. Gradually graft becomes small and can have fatty replacement, hydronephrosis, infarcts, hemorrhage or calcification.

Vascular Complications

Vascular complications in post renal transplantation have significant negative influence of graft survival. They are infrequent, occur in approximately 1%–2%; [10] but can cause sudden loss of renal allograft. Selective catheter angiography is the gold standard for diagnosis; however, it is invasive and may cause various complications. Hence it is not used as a screening tool but reserved for patients with inconclusive results on the noninvasive screening tests. Noninvasive imaging like ultrasound, Doppler, scintigraphy, CT and MR angiography plays major role to evaluate them.

Renal artery thrombosis (RAT)

Incidence: Ranges from 0.5% to 3.5 % [11] Imaging appearance: No evidence of any arterial or venous flow noted on color, spectral and power Doppler study (Figure 12). Doppler sonography had 100% sensitivity and specificity for diagnosis and hardly any other imaging study is required for diagnosis [12].

Figure 12: (A) Grey scale USG image, (B) Power Doppler image of transplanted kidney show enlargement and absent colour flow Suggest Vascular Thrombosis.

Focal Renal Infarction

Imaging appearance: A segmental infarct appears as a poorly marginated wedge shaped hypoechoic mass or a hypoechoic mass with a well-defined echogenic wall without colour flow (Figure 13). If the infarction is global, the kidney will appear hypoechoic and be diffusely enlarged.

Figure 13: Colour Doppler image of transplanted kidney shows absent colour flow (A) in upper and mid pole, (B) in upper pole favoring Segmental infarct.

Renal Artery Stenosis (RAS)

Incidence: It has wide range varying from 1% to 23 % depending on the definition and diagnostic techniques used.

Site: usually at anastomotic site

Imaging appearance: On gray scale USG, there is lack of normal post-transplant hypertrophy. On color Doppler study appearance of focal color aliasing noted at stenotic segments. On spectral Doppler study, peak systolic velocity in main renal artery >300 cm/sec and Ratio of PSV in transplanted main renal artery and external iliac artery greater than or equal to 1.8 are highly suggestive of significant stenosis. Indirect criteria are low resistive index <0.56, Acceleration time >0.07 sec, Acceleration index <3 meter/ sec and Intrarenal tardus–parvus waveform (Figure 14).

Figure 14: Spectral Doppler image shows (A) elevated peak systolic velocity in main renal artery at anastomosis, (B) delayed systolic upstroke and rounding of systolic peak consistent with tardus parvus spectral waveform in case of transplanted renal artery stenosis.

Limitation: Results are strongly depends on the operator’s individual experience and skill. Rate of restenosis is less than 10 %. Doppler ultrasonography is the procedure of choice to evaluate graft perfusion before and after revascularization The term pseudo transplant renal artery stenosis (TRAS) refers to thrombosis or stenosis of iliac artery or aorta proximal to transplant renal artery.

Renal vein thrombosis: (RVT)

Figure 15: (A) Grey scale USG image shows swollen and hypo echoic transplanted kidney, (B) Colour Doppler image shows absent venous flow and spectral Doppler image shows absent and reversal of diastolic flow in renal artery favoring Renal vein thrombosis.

Incidence: Ranges from 0.9% to 4.5 % [13]

Imaging Findings: Graft appears swollen and hypoechoic.

Doppler shows absent venous flow. Renal arterial Doppler spectrum shows absent or reversal of diastolic flow due to increased resistance (Figure 15). Reversal flow in renal artery is nonspecific as it also seen in severe rejection and in acute tubular necrosis, its combination with absent venous flow is the diagnosis of renal vein thrombosis. Partial thrombosis also can occur near anastomosis or within the transplanted kidney (Figure 16).

Figure 16: Spectral Doppler image shows (A) partial thrombosis in renal vein near anastomosis (white straight arrow), (B) partial thrombosis in main renal vein (white straight arrow) and adjacent renal pelvis showing DJ Stent (curved whited arrow) in two different cases. Intra renal venous flow is very well demonstrated and appears normal Suggest Partial renal vein thrombosis.

Extra parenchymal pseudo aneurysm

Incidence: Anastomotic pseudoaneurysm is a rare complication of renal transplantation occurring in 0.3%. [14]

Imaging findings : On gray scale ultrasound it appears as cystic lesion which shows color flow and to and fro spectral pattern on doppler study(Figure 17). Endovascular treatment with covered stent placement to exclude pseudoaneurysm can also be evaluated with USG and colour doppler (Figure 18).

Figure 17: (A)Grey scale USG image of transplanted kidney shows cystic lesion near anastomosis which shows color filling in Colour Doppler image(white arrow), (B) Colour Doppler image shows colour filled out pouching near anastomosis(white arrow) confirmed non thrombosed extra parenchymal pseudo aneurysm in two different cases.

Figure 18: (A) Two echogenic line structure(Stent) in main anastomotic renal artery in gray scale USG image of transplanted kidney, (B) Colour doppler image shows partially colour filled pseudoaneurysm at anastomosis with stent suggest Imaging findings of endovascular treatment with covered stent placement.

Intra-parenchymal arteriovenous fistula and pseudoaneurysm

AVF occurs when both artery and vein are simultaneously lacerated, while pseudoaneurysm results when only artery is lacerated. Incidence: 1-18% of the biopsies [15] Time of onset: occur at time of biopsy. They depend on many factors – ultrasound guidance, needle caliber and imaging follow up. Imaging appearance: colour Doppler study shows AVF as focal areas of disorganized flow adjoining the normal vasculature. Spectral waveforms show increased arterial and venous flow with high velocity and low resistance (Figure 19). Pseudoaneurysm appears as simple or complex cyst on B mode ultrasound and intracystic flow on colour Doppler mode (Figure 20).

Figure 19: (A) focal colour aliasing at lower pole of transplanted kidney in colour doppler image, (B) Spectral Doppler evaluation demonstrates high velocity, low impedance waveform with increased diastolic flow Suggest arteriovenous fistula (AVF) in doppler evaluation after biopsy.

Figure 20: (A) Grey scale USG image shows cystic lesion in lower pole of transplanted kidney in grey scale USG image, (B) colour Doppler image shows intra cystic flow Suggest intra parenchymal pseudo aneurysm.

Neoplasms after renal transplantation

Post renal transplantation patients are at higher risk of development of neoplasms. Urologic tumour are 4 to 5 times more common in post renal transplantation recipients than normal population with significant exposure to cyclophosphamide immunosuppressant agent.

Renal cell carcinoma

Etiology: by means of transplanted organ or de novo development by immunocompromised status, patients on hemodialysis in case of chronic renal failure develop acquire renal cystic disease Prevalence: 90 % occurring in native kidney and 10 % in transplanted kidney [16] Imaging appearance: lesion appear heterogeneous with vascularity, similar picture as seen in native kidney [17] (Figure 21).

Figure 21: Gray scale ultrasound image of transplanted kidney shows (A) heterogeneous mass lesion at the upper pole (white arrow) with internal hypoechoic region (asterisk) suggesting necrosis, (B) the mass lesion showed internal as well as peripheral vascularity on color Doppler study. Suggest renal cell carcinoma in transplanted kidney.

Lymphomas

Incidence: 1 % of renal allograft recipients [18] Time of onset: Post transplantation lymphoproliferative disorder is diagnosed at a median of 80 months after transplantation. Imaging appearance: Lymphadenopathy at various sites but can also affect any solid organ or hollow viscera or transplant graft parenchyma itself. It appears as low or mixed reactive masses and tends to have a predilection for the renal hilum.

Recurrent Native disease

It depends on the primary disease before transplantation. Imaging appearance: Imaging has no specific pattern in these situations apart from excluding the treatable cause of reduced renal function.

Abdominopelvic Complications

Renal graft is placed in extraperitoneal space via a peritoneal window in laparoscopic and robot assisted surgical techniques. So these cases are prone to same complications experienced by other surgical cases in whom peritoneum is exposed.

Renal Allograft Compartment Syndrome (RACS)

It is a rare syndrome, and it is under recognized cause of early transplant dysfunction or even loss. It may occur as a result of intracompartment hypertension and ensuring ischemia of renal graft [19]. Imaging appearance: absent or diffuse diminished cortical flow in transplant kidney at colour Doppler.

Fascial dehiscence and bowel or allograft evisceration

They tend to occur in perioperative period. Herniation of bowel through a transplant peritoneal defect may lead to compromise of intestine or transplant itself.

Limitations

The USG examination is examiner dependent and limited accessibility in obese patents impairs the evaluation and often leads misinterpretation. The RI index is also unspecific and influenced by many factors like site at which the RI is measures, increased intraabdominal pressure during forced inspiration and the pulse rate.

Summary

Kidney transplant is the treatment of choice for patients with end-stage renal disease. Improvements in surgical techniques and advanced immunosuppressive drugs have resulted in remarkable survival of patients and renal grafts. Still complications occur in both the early postoperative period and later. Kidney transplants follow up is common in radiology and sonography practice. Ultrasonography and Doppler examination can accurately depict and characterize many of the potential complications of renal transplantation. It facilitates prompt and accurate diagnosis and thus guiding treatment.

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Lupine Publishers|Inguinal Hernias Repair by Laparascopy (Pet)

Abstract

Introduction: The hernia affection is one of the processes that has been studied into much detail and whose treatment pursues excellence, although many controversies are still yet to be resolved. Laparoscopy repair of inguinal hernia is a treatment method that improves the quality of management given to our patients. Objective: To identify perioperative events, surgical complications and to evaluate the pain referred for the patients who have had inguinal hernia repair by the laparoscopic method. (TEP). Methods: A prospective and descriptive study was done on 80 patients who have had endoscopic (TEP) repair of inguinal hernias between January 2013 and December 2020. Results: We performed 100 hernioplastias by laparocoscopy in 80 patients. The male sex predominated in a 5:1 ratio and the surgical time average was, 53.5 minutes for unilateral hernias and 71.3 minutes for the bilateral ones. The most frequent complication in the transoperatory stage was ¨minor bleeding¨. At 15 days after surgery, 86.3% of the operated did not complain of pain, but social and laboral reintegration was at a 34% of the total. Conclusions: Laparoscopic inguinal hernioplasty is a good therapeutic option, mainly in patients with bilateral and reproduced inguinal hernias.

Keywords: Laparoscopic Hernioplasty; Inguinal Hernia; Hernia Recurrence

Introduction

Since the concept of endoscopic inguinal hernia repair was first described by Ger in 1982, endoscopic techniques have been modified; It was a time when failures and complications - coupled with high cost - outweighed initial enthusiasm [1]. Laparoscopic hernioplasty (LH) has gained popularity in the last decade and numerous controlled studies appear in the literature comparing laparoscopic techniques with conventional ones [2]. In recent years, HL, despite being one of the most controversial laparoscopic procedures, has established itself as a therapeutic option to consider. The advantages of this method are demonstrated in bilateral, recurrent hernias and in the labor-active subject, who requires early return to work [3].

Method

Between January 2013 and December 2020, a prospective, descriptive, longitudinal-cut study was carried out in 80 patients operated on by endoscopy (PET) with the diagnosis of inguinal hernia, at the General Teaching Hospital “Enrique Cabrera”. All patients who agreed with the type of surgical intervention, the study and who gave their informed consent were included; patients older than 30 years classified ASA I-III, without anesthetic contraindications for laparoscopic intervention and patients classified as Nyhus III and IV. Patients with previous surgical wounds in the inguinal region, to operate, not dependent on reproduced inguinal hernias and patients with complicated, irreducible or slipped inguinal hernias; they were excluded. The surgical techniques were: totally extraperitoneal laparoscopic inguinal hernioplasty (TEP). The PET technique was performed with some variants such as: no use of the balloon trocar, the preperitoneal space was decolorized by means of the 0º laparoscope and the insufflation of CO2 at 13 mmHg. In patients with large hernial rings, a polypropylene cone was placed in the hernial defect and subsequently a 15 x 12 cm polypropylene prosthesis. There was no need to fasten the meshes with clips [4]. In the immediate postoperative period, the visual pain scale analog scale (VAS) was applied and a pain value was assigned by means of “little faces”, which starts from very happy (I value) to very sad (X value). Pain quantification was repeated in consultation 7 days, 15 days and one month after the operation.

Results

100 hernias were operated on in 80 patients (20 patients [25%] had bilateral hernias, 85 primary hernias, and 15 reproduced hernias). The average age was 55.6 years, the youngest patient was 30 years old and the oldest was 77 years old, but the majority (14 patients) belonged to the fifth decade of life. The male sex predominated in 84%, which represented a male / female ratio of 5: 1. 43% of the patients made great physical efforts on a regular basis Table 1 shows that 36 patients had the habit of smoking, which represents 45% of the total and 17 consumed alcohol for 21.2%. Table 2 shows that right hernias were more frequent in 54.0% of the total; the indirect variety with great dilation of the annulus and destruction of the posterior wall (IIIb) was the most frequent (41 hernias). Nine femoral hernias and 15 recurrent hernias were operated on.The 100 surgeries were performed by PET technique (100.0%). Two of the patients in whom a PET technique was started had to be converted to a conventional prosthetic technique due to accidental perforation of the peritoneum, passing CO2 into the peritoneal cavity, and consequently, the loss of the preperitoneal surgical space, and another was the conversion of a failed PET technique. The mean surgical time for unilateral hernias was 53.5 min, with a minimum time of 25 min and a maximum of 120 min. In bilateral repairs, the average surgical time was 71.3 min, with a minimum of 40 min and a maximum of 110 minutes. The hospital stay was less than 24 hours in 70 patients (87.5%), in 5 patients it extended from 24 to 48 hours and in 5 patients it lasted more than 48 hours. Table 3 shows minor bleeding as the most frequent complication in the intraoperative period, in 22 repairs (22.0%) that originated 13 hematomas (13.0%). No complications were observed after the second week, but two patients suffered recurrences (2.0%) more than two months after the operation. Table 4 shows the pain classification according to the VAS scale. In the immediate postoperative period, after the patient recovered from anesthesia, 75 individuals (93.7%) were classified as VAS I and 5 patients as VAS II. At 24 h after the operation, 19 patients (23.7%) were classified as VAS I, 50 (62.5%) as VAS II, 7 patients as VAS III, and 4 as VAS IV. In the first week postoperative consultation, 52 patients (65.0%) were classified as VAS I and 15 as VAS II, and two patients with moderate pain (VAS V) appeared in this period. At 15 days after surgery, 69 patients (86.3%) were VAS I and at one month 73 (91.3%) were. The incorporation to the usual activities, including work, was of 3 patients (3.7%) a week after the operation, after 15 days there were 23 patients (28.7%) and at month 54 patients, for 67, 5% of the total.

Table 1: Toxic habits and personal pathological history (APP).

N= 80 COPD: Chronic obstructive pulmonary disease

Table 2: Distributión according classificatión to the Nyhus [5].

Thel total is 100 hernias operated on in 80 patients.

Table 3: Complications.

Table 4: Evaluatión of the Visual Analog Scale (VAS) [6].

N = 80

Discussion

Currently, with the improvement of laparoscopic techniques, inguinal hernia surgery is emerging as safe, feasible and as a good therapeutic option, regardless of the age of the patient; However, the preoperative evaluation of the individual must be correct and thorough, specifically the cardiorespiratory function, since with the TEP method a working space is created between the sheets of the transverse lamina, richly vascularized, so that the absorption and elimination of the CO2 is greater than that produced in the peritoneal cavity during pneumoperitoneum [7]. Although men predominated, there was a slight increase in women in the series with respect to other authors [8] In laparoscopic practice, the finding of hernial defects diagnosed during the intraoperative period is frequent, in men and women, the latter essentially with a history gynecological disorders. Although the usefulness of hernia repairs in asymptomatic patients is questioned in some articles, the authors consider that it would be beneficial for the patient, if conditions permit, to repair the hernial defect by the TAPP method [9]. The relationship between hernial disease and physical exertion has been classic since Cooper’s time. In the series, 68% of the patients performed physical activities that involved great and medium efforts and also analyzing the multifactorial nature in the pathogenesis of hernia disease, it is striking that approximately half of the operated patients were smokers, a factor that influences in collagen metabolism, significantly linked to hernia recurrences [10]. Most of the repairs were by means of the TEP technique and we consider, like other authors, that although the TAPP technique brings us closer to the area from a perspective familiar to the surgeon (peritoneal cavity) and facilitates the so-called “learning curve”; Hernia disease -because it is considered a parietal defectshould be given a solution from this same plane, to avoid the probability of serious complications of the intra-abdominal organs and to leave the transperitoneal method as a tactical resource when the totally extraperitoneal method is unsuccessful. (eleven) Average surgical time was similar to other series [12]. It is known that this tends to decrease when the surgical team gains in experience. The longest operating time recorded was in a patient, who started with a PET technique, but due to technical difficulties, he was converted to a conventional posterior repair. The main complications were related to minor intraoperative bleeding and postoperative hematomas. In 3 patients it was necessary to drain the hematoma due to the discomfort caused, however, in the rest of the patients with hematomas and seromas they were treated with conservative measures. In two patients, recurrence occurred 2 months after the operation, which was interpreted as a technical error [13,14]. Our results coincide with numerous studies that affirm less postoperative pain with the use of minimal access techniques, as well as a prompt socio-occupational reincorporation of patients [1,3,9,15]. Despite the fact that 70% and 93.3% of the patients at 1 week and 15 days after surgery, respectively, had no pain or minimal discomfort; only 18 individuals (30%) started their usual activities before 15 days. These results contrast with other studies that report a return to work and social activities between 10-15 days postoperatively, although it is likely that some sociocultural factors are influencing these results [1,16]. In the series there were no major intraoperative or postoperative complications, only minor bleeding and bruising. In most of the patients, before 2 weeks postoperatively, the pain disappeared, however, the return to social work activities after 15 days was low.

Conclusions

Laparoscopic inguinal hernioplasty was an effective therapeutic option, especially for patients with bilateral and reproduced hernias. It provided benefits to patients and families, the former joining work and social activities early.

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Lupine Publishers | Ranjana’s Indigenous Suture Material for McDonald’s Cervical Cerclage

Abstract

Introduction: Cervical cerclage has been advocated in cases of ‘cervical incompetence’. There is very little evidence on the material to be used for cerclage. Here we have used nylon wool over semicircular needle for cervical cerclage.

Material and Methods: 30 patients were included in the study. After a written informed consent, the patient was then taken for cervical cerclage suture application. The material used was dark colored nylon wool. The primary outcome was live birth rate of the baby where as the secondary outcome parameters included period of gestation at delivery, mode of delivery, length of hospitalization of the baby, NICU if required, requirement of another cerclage in subsequent pregnancies and the timing of removal of cerclage.

Results: Out of the 30 pregnancies 29 were singleton pregnancies and 1 was twin pregnancy. The mean gestational age was 16.3 weeks. The mean duration between the cerclage and delivery was 137.6 days. All children survived their hospital stay and were discharged to home. 11 patients came for management of subsequent pregnancy. Close USG monitoring was done while deciding for the cerclage.

Conclusion: The present study of patients who were applied McDonalds cervical cerclage suture using nylon wool sutures have shown satisfactory prolongation of the period of gestation. All the newborns apart from 1 fetus, survived and were discharged to home. The results are promising, and they show that nylon wool can be used for McDonald’s cerclage.

Keywords: Mid Trimester Abortion; Cervical Cerclage, McDonald Cerclage; Premature Labour

Introduction

Cervical cerclage has come a long way since it was first performed in 1902 [1]. It has been advocated in cases of ‘cervical incompetence’ which is a term defined by ACOG as “the inability of uterine cervix to retain a pregnancy in the second trimester in the absence of uterine contractions” [2] Cochrane review has suggested the reduction in the neonatal mortality following cerclage [3]. Different terms have been used for different types of cerclages. These include [1].

History indicated cerclage - It is a prophylactic cerclage done in an asymptomatic woman at 12-14 weeks with history of 3 or more premature labour or mid trimester abortions.

Ultrasound-indicated cerclage - On USG done between 14-24 weeks of gestation if the cervical length is less than 25 mm without any exposed fetal membranes then cerclage can be performed.

Rescue cerclage - In cases of premature cervical dilatation with exposed fetal membranes with discharge/bleeding the cerclage procedure can be done as a salvage procedure.

There are many methods of performing cerclage which have been well described in the literature and are time tested. However, more concerning issue is the material to be used in the procedure of the cerclage. There is very little evidence on the material to be used [1]. The material initially described, Mersilene tape, has been found to be associated with infection leading to failed cerclage and premature labour. This was followed by the use of mono filamentous suture material which was to avoid the infection. This infection may trigger premature labour [1]. The mono filamentous sutures have less suture strength and also due to the thinness of the suture it may cut through and damage the cervical tissues. Braided sutures (PDS - Polydioxanone) increase the strength but then the chances of infection are still there. The literature is divided in the ideal material to be used for the cerclage [4,5].This study is a prospective study which analyses the use of nylon wool as a suture material for the cerclage stitch along with the advantages which the author felt while using the same.

Material and Methods

This prospective study was performed in 30 patients at our centre between 1990-2019. The study constituted women for history indicated, ultrasound indicated or rescue cerclage from 12- 24 weeks of gestation with the inclusion criteria of

a) H/O 3 or more previous mid trimester abortions or premature (<28 weeks) births

b) H/O mid trimester abortion with shortened cervix

c) Ongoing pregnancy with impending abortion

Women who were unwilling to participate in the study were excluded.

After discussing the potential risks of the surgery, the procedure was explained in non-medical terms and after getting a written informed consent the patients were included in the study.

All the patients underwent a thorough physical examination and co-morbidities if any were taken into account. A detailed previous history and that of the drug usage in the current pregnancy was taken. Routine blood examination was done. Vaginal and Urinary tract infection was also ruled out. An ultrasound examination was done to assess the cervical length. The patient was then taken for cervical cerclage suture application.

The material used was dark colored nylon wool. The threading of the wool was done through semicircular round body needle (No12) after wetting the end of the wool which helped in threading. Doubling of the wool was done. The wool was then wrapped around the needle and autoclaved for sterilization [Figure 1].

McDonald’s method [6] was used for cervical cerclage in all the cases with 2 layers (by doubling the nylon wool thread) of the suture material. All cases were performed under General Anesthesia. A short course of broad-spectrum antibiotics (2 doses) was administered to the patient. The patients were kept under tocolytic support in the form of Isoxsuprine intravenous continuous infusion in Dextrose normal saline fluid (10 mg over 24 hours for 2 days followed by oral Isoxsuprine 5 mg thrice daily and progesterone (Dydrogesterone 10 mg twice daily) till 34 weeks of gestation. All the cases were performed by the same surgeon and the patient was discharged home after 5 days.

Repeated USG examination (every 4 to 6 weeks) was done to monitor the progress of the cervical length and to decide the method of delivery. If elective cesarean section was planned, then the cerclage sutures were not removed till the procedure was performed. In case for a trial of natural delivery the sutures were removed at 36-37 weeks or onset of labour whichever was earlier.

The primary outcome was live birth rate of the baby whereas the secondary outcome parameters included period of gestation at delivery, mode of delivery, length of hospitalization of the baby, NICU if required for the baby, requirement of another cerclage in subsequent pregnancies and the timing of removal of cerclage.

In 1 case rescue cerclage was done at 18 weeks of gestation as the patient had come with an impending abortion with 4 cms dilatation of the cervix. This was attempted after all the pros and cons and the chances of procedure failing were explained to the patient.

There was a single case of twin pregnancy. She spontaneously delivered a premature baby with the cerclage suture in place. The second twin was in transverse lie and LSCS was done after suture removal. No untoward effect was noted on the cervix (bleeding, cut through).

Statistical Analyses: All the calculations were done with the help of SPSS version 23 software.

Ethical Approval - The study was designed and started in 1990 at that time the ethical approval was not required and hence, not taken.

Results

Thirty patients were included in the study period. Table 1 shows the baseline maternal characteristics. Out of the 30 pregnancies 29 were singleton pregnancies and 1 was twin pregnancy. The mean age of the patient was 31 years (23-38 years) [Table 1].

Table 2 shows the mean gestational age when the cerclage was done. The mean gestational age was 16.3 weeks (14-20 weeks). Out of the 30 pregnancies history indicated were 12 (40%), USG indicated were 17 (56.7%) and rescue cerclage was 1 case (3.3%). On physical examination only 1 patient had dilatation of cervix along with prolapse of the fetal membranes in whom rescue cerclage was done. In no case rupture of membranes occurred during surgery [Table 2].

Table 3 lists the outcomes of the pregnancy and the perinatal period. No immediate post cerclage premature rupture of membranes was seen. The patient in whom rescue cerclage was attempted the progress of abortion could not be halted and the patient aborted. In the remaining patients no delivery prior to 32 weeks was seen. The duration between the cerclage and delivery ranged from few hours (rescue cerclage) to 146 days. Normal delivery was carried out in 17/30 (56.67%) of the cases. Whereas, 13/30 (43.33%) underwent cesarean section. Even though, there was 1 abortion still 30 babies were delivered as in twin pregnancy one baby was delivered by normal delivery and the other by LSCS as the baby was in transverse lie. In 1 case the patient came in active labour the knot was cut but the whole suture material could not be removed as the cervical tissue was oedematose and in another case the patient wanted to continue with the cerclage in place and LSCS was done. This was followed by another baby by LSCS 2 years later and then the suture was removed [Table 3].

Table 4 lists the outcomes of the 30 live neonates as there was 1 abortion and 1 twin pregnancy. All children survived their hospital stay and were discharged to home. No neonatal / infantile deaths were noted during the study. In the case of rescue cerclage, the abortion could not be prevented. 2 neonates (2 twins) were below 1.5 kgs and both had to be admitted in the neonatal ICU and were released after 30 days [Table 4].

Table 5 consists of 11 patients who came for management of subsequent pregnancy, these pregnancies were not included in our data. Close USG monitoring was done, and the decision was made not to take the history into consideration while deciding for the cerclage. In only 2 patients the cerclage stitch was required again [Table 5].

Discussion

The present study of patients who were applied McDonalds cervical cerclage suture [6]. using nylon wool sutures have shown satisfactory prolongation of the period of gestation. All the newborns apart from 1 fetus whom we tried to salvage by rescue sutures, survived and were discharged to home.

McDonald’s cerclage is the most common intravaginal procedure used for cervical incompetence [7]. It is more popular than Shirodkar technique [3]. However, the type of suture material has never been discussed. Even RCOG in their green top guidelines have mentioned that the material to be used depends on the surgeon [1]. According to the American College of Obstetrician and Gynecologists, a non-resorptive material should be used for the McDonalds stitch [2]. The maximum data available is the use of mersilene tape [8] and monofilament sutures [9, 10]. However, the advantages of the suture material have never been fully assessed. Sato et al. [11] got promising results by using absorbable monofilament sutures for emergency cerclage but in their study the average birth weight of the baby was low, and the babies were premature which makes us think whether the premature labour was caused due to the loss in the tensile strength of the cerclage suture. Berghella et al [12]. compared braided polyester thread and Mersilene tape and found no difference in the outcome. Bernard et al [13] used braided sutures and found the results to be encouraging. Abdelhak et al [14]. compared delayed absorbable sutures with non-absorbable sutures. It was found that the delayed absorbable sutures were better as there was no need to remove them surgically.

In this study 30 patients were taken and the indication for the cerclage stitch was decided using either the history / examination method or the Ultrasound cutoff of the cervical length. 1 case of rescue cerclage was attempted but it failed in preventing the abortion. The twin pregnancy patient had both children who were premature babies and were admitted to the NICU. At the end of 2 years the milestones and intelligence is normal of both the babies. All USG imaging were done by the same radiologist to avoid any inter observer variation. All the surgeries were performed by the same surgeon using the same technique in all the cases to avoid any changes in the techniques. No rupture of membranes occurred during the procedure.

The advantages which the surgeon felt for the nylon wool were

a) Good tensile strength

b) No incidence of the cutting through of the suture.

c) Stretchability of the material

d) Inexpensive

e) Easily available

f) No incidence of infection

The requirement of cerclage for the second pregnancy was decreased as the cervical length was maintained and did not decrease the second time. This may have been due to fibrosis developing in the cervix leading to the increased tone of the cervix and also the maintenance of the cervical length. So, it is better to closely follow the cervical length on transvaginal ultrasound, rather than going in for repeat cerclage.

The cerclage was performed with 2 layers of the wool. This helped in increasing the strength of the suture and was a sort of safety measure even though single layer might have been enough. There was also no cut through of the suture through the cervical tissue. This may have been due to the stretchability and thickness of the suture material.

The patient in whom the cerclage stitch was not fully removed was because of the suture material embedding in the oedematous gravid cervix as the patient came in active labour. After 2 months of delivery the remaining suture material was removed as the embedded suture was now visible due to decrease in the oedema. All the patients were examined from time to time and on examination of the patient there was no inflammation or signs of infection around the wool. This suggests that the wool is inert and there is no infection/inflammation surrounding it.

In the management of twin pregnancy at 32 weeks the first baby was delivered per vaginum with the cerclage suture in place which was possible due to 2 reasons. First, the baby was premature and so the size of the baby was small. Secondly, the elasticity of the wool allowed the baby to be expelled out without any damage to the cervix. The neonatal outcome of the cerclage was good as the outcome was favorable in nearly all the patients.

This study is significant as it gives the information regarding the subsequent pregnancies and how the patients fared in the follow up pregnancies. However, there were also a few limitations of the study. Firstly, as it is not a comparative study hence, we cannot really assess whether this material is better than the one which are currently being used. Second, the sample size is quite small even though it is bigger than the other studies, but still larger studies are required.

Wool is a naturally antimicrobial. Wool is blended with synthetic material like nylon which increases the durability, stretchability and water wicking characteristics [15]. In our study we have used nylon wool, which classifies as braided suture material but because of the above mentioned properties less incidence of cut through and no infection was seen.

Conclusion

This study was undertaken to assess the use of indigenous cervical cerclage suture material - nylon wool for cervical cerclage. It gives the experience of a single center and even though the sample size is less, it is still adequate to provide a good analysis on nylon wool as a material suitable for cervical cerclage. The results of this study provide a favorable outcome of cervical cerclage with the use of nylon wool without any side effects. However, further comparative studies using different materials will analyse how this material fares as compared to the other materials.

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Lupine Publishers | Magical Hands of a Tribal Farmer Set a Milestone in Finger Millet Cultivation-A Case from Koraput, Odisha, India

Abstract

The nutritious millets traditionally occupied substantial part of the diets and cropping systems in tribal areas of Odisha. Millets require less water and are more resilient to climate vulnerability. They can also be cultivated on the undulating terrain. Reduction in millets resulted in nutrition deficiency. In order to address growing crop failures and nutritional issues, millets need to be revived. Majority of the farmers in Koraput district of Odisha are tribal, resources poor and mostly dependent on onset of monsoon for agriculture. The rainfall in this region is erratic and prolonged drought conditions are common occurrences. Numbers of rainy days were decreased over the period of time. Millets being climate resilient crops systems, revival of millets will enhance resilience of the farming systems and household food security against Climate Change. Finger millet is the second staple food after rice. Area under millets is drastically declining resulting in narrowing of the food diversity in consumption at household level. Increasing urban demand, improvements in processing machinery, availability of improved cultivars, better agronomic practices and possibility of accessing support irrigation has increased the potential of realizing higher productivity in millets thereby improving nutrition security, resilience and economic security of tribal households. The farmers were cultivating many traditional varieties in the past, but now have changed to improved varieties because the traditional varieties continuously perform low in terms of productivity due to mixture of seeds, loss of purity and long duration. This paper analyses how a tribal family set a milestone in finger millet by adopting improved agronomic and good agricultural practices (Figure 1).

Keywords: Cropping System; Nutrition Deficiency; Climate Resilient Crop; Koraput; Seeds

Introduction

Odisha is predominantly an agricultural state with a cultivated area of 90.54 lakhs ha and average production of 25.44 million tons. Koraput district comes under Eastern Ghats high land type agroecological zone. The district enjoys tropical climate characterized by hot summer (20.5°C to 38°C), cold winters (12 °C to 29 °C and rainy seasons (19 °C to 28 °C). The winter season generally commences from late November and continues up to the end of February. The summer season commences from March and continues till middle of June. It is observed that about 80% of the total annual rainfall takes place due to south-west monsoon between the middle of June and mid-October. The north east monsoon gives erratic and insufficient rainfall. The average annual rainfall varies between 1320-1520mm (Figure 2 & 3). Although the district is having high rainfall, the number of rainy days is restricted to 70-80 days/ annum. The district is drought prone because of the erratic and uneven pattern of rainfall. The entire Koraput district has a unique physiographic set up. Except the north western and west-west central part, the rest of the district is occupied by dense forest with highly rugged mountains, interspersed with intermundane valleys. The total geographical area is 8,807 Sq. Km. The population of Koraput district as per 2011 census 1,379,647 of which male and female were 678,809 and 700,838 respectively with the schedule caste population is 196540 (14.2.%) and schedule tribe population 697583 (50.6%). The literacy percentage of the district is 49.29 as against 72.9 of the state. Population density is 157/km2. The proportion of district population to the Odisha state population is 3.29%, Sex Ratio (Per 1000) 1032: 999. The total cropped area is about 3.56 lakh ha out of which 1.53 lakh ha (43.0% of TCA) is irrigated and 2.03 lakh ha (57.0% of TCA) is under rain fed area. The main sources of irrigation are canals, rivers, farm ponds, dug wells to net sown area of the district. Among the different crops, cereals accounts for 54.5% of the irrigated area followed by other crops (34.6%), coarse cereals (4.7%), horticulture & plantation (2.9%), pulses (2.5%) and oil seed crops (0.7%). The primary source of income is from Agriculture whereas secondary source from agriculture labourer and daily wages. Kharif is the major cropping season where farmers cultivate cereals, millets and pulses. In Rabi season few pulses crops, oil seed crops and vegetables are being cultivated and majority of the farmers migrated in search of wage labourer both within the district and outside the district. The majority of farmers hold less than one hectare of land in the district and generally practice subsistence farming. Rice is the major crop cultivated in the district in Kharif and also in Rabi where irrigation facilities available. Traditional farm practices are followed in upland resulting in low level of production. In the non-agriculture season NTFP like kendu leaf, tamarind, Mohua and Sal seeds are the source of income. Koraput was recognized as a Globally Important Agricultural Heritage Systems (GIAHS) by FAO in 2012 for the efforts of the community in biodiversity conservation, food security, preserving the traditional wisdom and cultural diversity of the region for the benefit of the present and future generations (Figures 4-6).

Koraput is a tribal dominated district in Odisha consisting of more than 70% small and marginal farmers and 83% of population live in Below Poverty Line (Anonymous, 2013). The most dominant tribes in this proposed operational area are Bhumia, Gadaba, Paroja and Kandha. Subsistence farming still remains their main source of livelihood, supplemented by forest collection and earning wages [1]. The tribal income is mainly based on agriculture and forest products. The per capita income of the district is Rs 25161/ annum (source: Odisha Economic Survey 2014-15). Though the district is rich in biological resources, experienced & hard working farming communities, existence of Women Self Help Groups and the standard of living is quite low due to poor farm productivity, lack of village level small scale industries, low level of technological knowhow and lack of market knowledge. Foreseeing the sustainable yield in finger millet, M. S. Swaminathan Research Foundation launched a project on “Enhancing Production and Productivity of Millets and Pulses in Odisha through an Alternative Seed System Model for Production and Supply of Improved Seed Varieties” with support from Department of Agriculture & Food Production, Govt. of Odisha and Govt. of India under the scheme Rastriya Krishi Vikash Yojana (RKVY) in April 2018. The project was executed in 13 villages of Umuri, Mastiput, Padampur and Lankaput Gram Panchayat in Koarput district involving around 750 farmers. The project introduced new technology like System of Millet Intensification (SMI) and line transplanting. Participatory Varietal Selection was conducted with six traditional varieties and five improved varieties of finger millet. The farmers observed that among all the varieties cultivated, KMR-204 performed better in terms of no. of productive tillers, size of panicle, fingers per panicle, grain filling percentage and grain yield (Figures 7 & 8).

Materials and Methods

Hari and Gori used to cultivate finger millet in one acre of land following traditional practices. They used to follow broadcasting method. Weeding also was a very tedious task for them. They used to harvest 2.5 to 3.0 quintals from it. During last Kharif MSSRF implemented the seed production programme in the village. They were trained on various improved agronomic practices and System of Millet Intensification (SMI) method of cultivation such as - land preparation, FYM application, seed treatment, raised bed nursery preparation, transplanting in SMI method, organic manure and bio pesticides preparation and application, use of cycle weeder for weeding etc. Shri and Smt. Sukia were provided with 500 grams of breeder seed of KMR-204 variety to cultivate in half acre land. Initially they were little bit scared [2]. So, they decided to try in half acre and the rest half acre they cultivated their own variety Bati Mandia following traditional method. They followed all the recommended agronomic practices stated above and also followed organic way of cultivation. They also prepared NPM like Amrut jal, jeebamrut, handi kahata etc. and applied in their millet field in every 15 days interval after weeding using cycle weeder which helped in plant growth and controlling pests and diseases (Figures 9 & 10).

Study Design

A case study

Study Location

Machhara village of Koraput block, Koraput District, Odisha, India

Duration of study

June 2018 to December 2019

Results and Discussions

Despite the un-conducive weather condition during last kharif season, the crop performed very well. There were productive tillers in a range of 8 to 25 per hill. An average finger per panicle was around 9 which is higher than that of other farmers cultivating same variety (Table 1). Hari and his wife were very happy and surprised to see the crop performance of the new improved variety in comparison to her own traditional variety. They yielded 3.4 quintals/ acre from their own variety of bati mandia following traditional practices and 20.55 quintals/ acre from the improved variety i.e. KMR-204 following SMI method and improved cultivation practices (Table 2 & 3). They never dreamt of getting such a bumper yield from the improved variety. Now she is convinced that she will use the seeds of this variety in coming years and also say others to follow the same practice. She sold the foundation seeds of 400 kg @ Rs 40/- per kg and shared around 250 kg to her relatives for seed purpose and remaining grains she kept for own consumption (Figure 11). The cultivation cost was around Rs 6200/- INR for half acre. The net benefit she got after meeting all the cost of cultivation was Rs. 27,400/- INR from the same land of half acre (Table 4-6).

Conclusion

The study clearly reveals that millet is not a poor man’s crop. If it is cultivated with proper care in up or medium land following improved agronomic practices, it can compete with any other crop and produce good yield with very low input cost of cultivation. Inclusion and promotion of modern technological intervention like SMI is an advantage to the finger millet. So, it is proved that millet cultivation can be a viable alternative and sustainable option for the rural poor. Moreover, it is eco-friendly and improves food security and enhances economic growth. She is now a role model who can serve to the community by extending her knowledge and experience to promote millet in the region with a new hope.

Acknowledgement

The authors sincerely thank Department of Agriculture & Food Production, Govt. of Odisha and Govt. of India, RKVY team who supported us to implement this project. Our special thanks are due to Dr Krishnakumar K. Navaladi, Director, Biju Patnaik Tribal Agro-biodiversity Centre, MSSRF, Jeypore for motivation. Special mention of appreciation goes to the farmers of Koraput block who co-operated and adopted the technology and staff members and volunteers who guided the farm families in implementing this alternative seed system project successfully

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Lupine Publishers | Magical Hands of a Tribal Farmer Set a Milestone in Finger Millet Cultivation-A Case from Koraput, Odisha, India

Abstract

Keywords: Cropping System; Nutrition Deficiency; Climate Resilient Crop; Koraput; Seeds

Introduction

Materials and Methods

Study Design

A case study

Study Location

Machhara village of Koraput block, Koraput District, Odisha, India

Duration of study

June 2018 to December 2019

Results and Discussions

Conclusion

Acknowledgement

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LupinePublishers|The Current Approach to the Hepatocellular Carcinoma; A Mini Review of Etiology, Prognosis and Treatment

Short Communication

One fifth of the population in UAE suffers from gastrointestinal diseases including obesity, reflux disease and fatty liver because of obesity, poor diets and close marriage, Acid reflux, ulcerative colitis and irritable bowel syndrome are increasing in recent years [1-3]. There are also a high number of sufferers of fatty liver, caused to a large extent by the excessive consumption of sugary drinks. Obesity is an issue that can affect the UAE’s development as a nation and needs to be managed immediately and effectively, vague discomfort is usually the only symptom of a fatty liver. Low fiber diets, lack of exercise and consuming large amounts of food and dairy products are responsible for the majority. Genetics combined with obesity are responsible for people suffering from many disorders. A case of fatty liver, if ignored, might escalate to an advanced liver problem later in life.

Increasing numbers of inflammatory bowel diseases specially in the young and more severe forms of Crohns disease. Increasing numbers of cancers especially colorectal cancers affecting younger populations. During our practice in UAE we came across many rare and unusual disease presentations that were missed because of either lack of awareness or failure to check detailed history including family history and proper physical examination. These diseases included: Celiac disease which affect 2.3% of the population, Inflammatory bowel diseases both ulcerative colitis & Crohns disease with obvious rise in Crohns disease, Studies on colorectal cancer showed that over 60% are discovered in an advanced stage and affecting younger populations and because of that the health authorities started the program to prevent, early detect colorectal cancer. Our initial study of over 6000 colonoscopies showed prevalence of polyps over 30% and colorectal cancer in about 1% of all colonoscopies,20% of colorectal cancers were below the age of 40 years. Many families with inherited colorectal cancers including Lynch syndrome were seen. Constipation is a real problem in UAE sometimes ending in severe disability and sometimes colectomies performed for some refractory cases. Missed diseases included over 10 cases of multiple auto immune IGG4 related diseases that presented as pancreaticobiliary manifestation or multiple auto immune diseases, pachymengitis & mesenteric panniculitis. Many cases of hyper elasticity syndromes associated with reflux disease & 10 cases of vascular compression syndromes mainly superior mesenteric artery syndrome [4-10]. 4 cases of Behcet disease with intestinal involvement, 3 cases of Cowden disease, 2 cases of tylosis with reflux disease and esophageal & colon cancers, 1 case of Gardner syndrome. 1 case of Chédiak–Higashi syndrome syndrome with albinism & colitis. We are running monthly meetings for these unusual presentations of common diseases and rare diseases in UAE. Awareness for young colleagues in all specialties is needed in these diseases [11].

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