Alzheimer’s research ‘world first’: blood oxygen levels could explain why memory loss is an early symptom
In a world first, scientists from the University of Sussex have recorded blood oxygen levels in the hippocampus and provided experimental proof for why the area, commonly referred to as ‘the brain’s memory centre’, is vulnerable to damage and degeneration, a precursor to Alzheimer’s disease.
To understand why this region is so sensitive, the University of Sussex researchers, headed up by Dr Catherine Hall from the School of Psychology and Sussex Neuroscience, studied brain activity and blood flow in the hippocampus of mice. The researchers then used simulations to predict that the amount of oxygen supplied to hippocampal neurons furthest from blood vessels is only just enough for the cells to keep working normally.
Dr Catherine Hall, Senior Lecturer in Psychology at the University of Sussex says:
“These findings are an important step in the search for preventative measures and treatments for Alzheimer’s, because they suggest that increasing blood flow in the hippocampus might be really effective at preventing damage from happening.
“If it’s right that increasing blood flow in the hippocampus is important in protecting the brain from diseases like Alzheimer’s, then it will throw further weight behind the importance of regular exercise and a low-cholesterol diet to long-term brain health.
“We think that the hippocampus exists at a watershed. It’s just about OK normally, but when anything else happens to decrease brain blood flow, oxygen levels in the hippocampus reduce to levels that stop neurons working. We think that’s probably why Alzheimer’s disease first causes memory problems – because the early decrease in blood flow stops the hippocampus from working properly.
“The same factors that put you at risk of having a heart attack make you more likely to develop dementia. That’s because our brains need enough blood flow to provide energy – in the form of oxygen and glucose – so brain cells can work properly, and because blood flow can clear away waste products such as the beta amyloid proteins that build up in Alzheimer’s disease.
“Now we want to discover whether the lower blood flow and oxygen levels in the hippocampus are what causes beta amyloid to start to build up in Alzheimer’s disease. Understanding what causes early damage will be really important to help us learn how to treat or prevent disease.”
Dr Kira Shaw, a psychology researcher at the University of Sussex who undertook the main experiments, said:
“We found that blood flow and oxygen levels in the hippocampus were lower than those in the visual cortex. Also, when neurons are active, there is a large increase in blood flow and oxygen levels in the visual cortex. This provides energy to hungry neurons. But in the hippocampus, these responses were much smaller.”
The scientists also found that blood vessels in the hippocampus contained fewer mRNA transcripts (codes for making proteins) for proteins that shape blood vessel dilation. Additionally, the cells that dilate small blood vessels, called pericytes, were a different shape in the hippocampus than in the visual cortex.
Dr Shaw concluded: “We think blood vessels in the hippocampus are less able to dilate than in the visual cortex”.
The research results point to differences between the microbiome of "larks" and "owls"; among "larks," the researchers found a higher percentage of the bacterial genus Alistipes, whereas among "owls," the bacteria belonging to the Lachnospira genus were higher—bacteria that produce butyrate, a short-chain fatty acid that is a source of signals related to sleep and wakefulness.
A collaborative research project between the University of Haifa and the Technion–Israel Institute of Technology has found that “morning people” and “night people” differ from each other in their gut microbiome—the bacterial populations that inhabit the digestive tract.
The study was conducted in collaboration between researchers and a number of research groups at the University of Haifa and the Technion: Assoc. Prof. Eran Tauber Head of the Biological Clock Lab in the Department of Evolutionary and Environmental Biology at the University of Haifa and his lab manager Dr. Bettina Fishman, Prof. Tamar Shochat and research student Liel Stelmach Lask of the Cheryl Spencer Department of Nursing at the University of Haifa, and Dr. Naama Geva-Zatorsky, Head of the Microbiome Research Lab of the Rappaport Faculty of Medicine at the Technion, and her Ph.D. student Shaqed Carasso. The challenge was to examine differences in gut microbiome composition between early risers and night people.
“This is the first time that a connection has been found between people’s gut microbiome, eating behavior and sleep patterns,” says Prof. Tauber. “These discoveries are likely to pave the way to change these patterns by altering one’s diet.”
I saw Jake Muller listed above Chris on some poll ranking RE protagonists according to skill and this could be a fun take. Thoughts on Jake?
!! Truly!? Says who?
Never have I been so insulted for Chris, and I've made quite the practise of it throughout the whole of the series. Jake is just so green. To consider that he has more skill after one game...
Thoughts on Jake Muller:
Quite frankly, I still am not the biggest fan of the idea that Wesker has a biological child through means of an implied relationship. Jake has a mother, mentions her, but we are still left to try and fathom who this woman is. Consider the following: Wesker has caches of bioweapons [specifically, Uroboros] and literal loads of research stashed away. Any of these jumbles of letters that call themselves anti-bioterror organisations would likely have tracked his movements to the best of their abilities.
We are told to believe that there is no canonical record of Wesker being in a relationship with an Edonian woman who had emigrated to [presumably] Raccoon City? I also am unsure if Jake can rightfully claim the “dead beat” father excuse for his behaviour if his mother moved back to Edonia prior to giving birth, but I should digress... I won’t.
Born in 1992, Jake grows up with a single mother who falls ill in the early 2000s. In an effort to support his mother through her illness, he becomes a mercenary. Here is the bit where I find that he is “more skilled” than Chris to be erroneous, and highly insulting: According to the Resident Evil 6 Memo “Soldiers of Fortune”, Jake knew nothing of combat skills until he joined his first mercenary group at seventeen. This means that Jake’s skillset has been active for an entire THREE YEARS before the Edonian Civil War and the Lanshiang Incident. It is an utter travesty to say that Jake Muller is more skilled than Chris after only having been trained for three. years.
He became attached to his CO, who taught him how to fight-- and his new father figure promptly sold out the unit as a turncoat. I suppose that being somewhat of Jake’s father makes you liable to be a traitor.
Furthermore: Canonically, Jake is “moody”, “distant”, “cold”, and has no loyalties to any cause. If you’ve played Six, you know this already. But, we cannot take into account a character’s popularity without examining their convictions.
From here on, what we know of Jake takes place in-game. Foolish boy, making foolish decisions. He does have a bit of a redeeming arc, but that arc takes place solely through Sherry and uses her as his motivator. I am not so enthralled that she functions as his catalyst for change. In the course of six months, during which he’s run from Ustanak, endured some experimentation, and somehow picked up an entire Cantonese vocabulary-- he goes from “pay me millions for a blood sample”, to “there are more important things at stake than you and I”.
His feud with Chris is utterly imaginary and it shows just how immature he is as a character. He blames Chris for taking his father away from him, but Jake never had his father. He never knew who his father was. In the same breath as learning Wesker’s name, he learns that he was a bioterrorist of the highest calibre. He is anger with Chris for killing an imagined version of what he wanted Wesker to be. And nearly shot him over it. Subduing the feud for the sake of mankind, quoted above, hardly saves it. This is because, I think, it feels oddly one-sided. We’ve followed Chris through all of these years and installments. We know and realise that killing Wesker was needed and quite justified. But then Jake comes along with a complex, attempting to put some sort of spin on the morality of killing Wesker.
What if the bioterrorist you are after has a child? Would you still pursue them? Yes, you would. Because they’re an active bioterrorist! Because they have the intent of ending the world through the use of a tentacle-virus and actively wants to put eugenics into practise because “everyone else is just so much chaff”. Not to mention- Jake does not know his father! He would never know his father! Even if Wesker had known that he had a son [again, we still believe this to be a stretch], I have high doubts that he would have cared enough to know him. He’s much too busy becoming a god and killing his own father figure. This entire father-son dynamic that Jake is angry over is entirely imagined.
I cannot offer much more of an analysis on him due to the lack of back story. And likely, the lack of his resurgence into the series. Capcom has a problem- they feel Chris needs to be replaced. They were going to replace him with Piers, but thought against it. They were going to replace him with Jake, but Jake’s reception was so poor that it would hurt the future of the franchise. And honestly, thank every denomination of God that Capcom thought better of it.
Could you imagine Village with Jake in Chris’ place? Some idiotic smart mouth trying to talk down sentient mould? Ugh. Spare me the thought.
Honestly, I am quite sad because I feel that due to Jake’s poor reception, and that Sherry is now regrettably tied to him, we may never see Sherry again. If that is the case, she is wasted. I will not forgive him if he wastes my daughter’s potential.
In short: Who performed the study, what was the sample size, what was the demographic that comprised it, and who calculated the confidence interval incorrectly? Jake more skilled than Chris... Please.
Star-shaped brain cells may be linked to stuttering
Astrocytes — star-shaped cells in the brain that are actively involved in brain function — may play an important role in stuttering, a study led by a University of California, Riverside, expert on stuttering has found.
“Our study suggests that treatment with the medication risperidone leads to increased activity of the striatum in persons who stutter,” said Dr. Gerald A. Maguire, professor and chair of the Department of Psychiatry and Neuroscience at the UCR School of Medicine, who led the study. “The mechanism of risperidone’s action in stuttering, in part, appears to involve increased metabolism — or activity — of astrocytes in the striatum.”
Findings from the study, published in Frontiers in Neuroscience, were borne from a collaboration between Maguire and Shahriar SheikhBahaei, an independent research scholar at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke.
The striatum is a key component of the basal ganglia, a group of nuclei best known for facilitating voluntary movement. Present in the forebrain, the striatum contains neuronal activity related to cognition, reward, and coordinated movements.
Stuttering, a childhood onset fluency disorder that leads to speech impairment, is associated with high levels of the neurotransmitter dopamine. Risperidone works by blocking the receptors in the brain that dopamine acts on, thus preventing excessive dopamine activity. Risperidone is available by prescription under a physician’s order almost anywhere in the world. In existence for nearly 30 years, it is generally prescribed for schizophrenia and bipolar disorder.
Maguire and SheikhBahaei have now found evidence that astrocytes in the striatum may be crucially involved in how risperidone is able to reduce stuttering.
“We do not know the exact mechanism for how risperidone activates astrocytes in the striatum,” said coauthor SheikhBahaei, an expert on astrocytes, and a person who stutters. “What we know is that it activates astrocytes. The astrocytes then release a signaling molecule that affects neurons in the striatum by blocking their dopamine receptors. In our future work, we would like to find this signaling molecule and better understand the exact role astrocytes play in stuttering, which, in turn, could help us design drugs that target astrocytes.”
Maguire and his team conducted a randomized, double-blinded placebo-controlled clinical trial with 10 adult subjects to observe risperidone’s effects on brain metabolism. At the start of the study and after six weeks of taking risperidone (0.5-2.0 mg/day) or a placebo pill, the 10 participants were assigned to a solo reading aloud task. The participants then each underwent a positron emission tomography, or PET, scan. It turned out that five subjects got risperidone while the other five got a placebo. Those in the risperidone treatment group were found to show higher glucose uptake— that is, higher metabolism — in specific regions of the brain according to scans taken after active treatment.
“Naturally, and abnormally, glucose uptake is low in stuttering — a feature common to many neurodevelopmental conditions,” said Maguire, who also is a person who stutters. “But risperidone seems to compensate for the deficit by increasing the metabolism, specifically, in the left striatum. More research is needed to understand this better. Neuroimaging techniques we used to visualize changes in the brains of those who stutter can provide valuable insights into the pathophysiology of the disorder and guide the development of future interventions.”
Next, Maguire and SheikhBahaei will aim to further understand what causes stuttering, what the different types of stuttering are, what may be their etiologies; and develop targeted personalized treatments for those who stutter.
“The general goal of our research collaboration is to combine basic research in my lab with Dr. Maguire’s clinical studies,” SheikhBahaei said. “My lab is generating new animal models to study stuttering which will help us understand what causes different types of stuttering. Researchers have proposed other components are involved in stuttering’s etiology. Our data, which suggests astrocytes in the striatum may be playing an important role in the development of stuttering, helps unify some of the findings the scientific literature has seen recently on astrocytes and could help connect the dots.”
Hello, friends! My responsibilities for my trading company job have abated in the interim, so I thought perhaps I would come back around to Jill, as promised.
Thoughts on Jill Valentine:
I will begin this by saying that it is appropriate that she was asked alongside Mia because there is one outstanding issue that I have between the both of them: The need to be saved. Though I find Jill to be leagues more competent.
We’ll get to it in full a bit later.
I will make no secrets that Jill has never been my most favourite of protagonists. Most of those issues stem from “3: Nemesis” and Five, though I am not adverse to including bits from One and Revelations. In one word, Jill is tolerable. Though, if given a choice (depending upon who my choices are) I will usually pick someone else.
A bit of background on Miss Valentine: I am utterly convinced that Capcom has changed her birthdate. I remember quite vividly scoffing that they made her birthdate Valentine’s Day, but now that I look it up again it seems its in May. Well, that’s at least a half a point in her favour. It’s become less mind-numbingly stupid. She is French-Japanese-American, whose father was a professional thief. In addition, she received Delta Force training through the US Army. Unusually adept at lock-picking, she then (apparently) gains the moniker - the Master of Unlocking. She also, again apparently, is adept at bomb disposal, though I cannot remember an instance in which this is exhibited. Though I can remember many instances when this would have come in handy. Jill.
Post-Delta Force and US Army tenancy, Wesker recruited Jill for STARS - described as an elite special forces operation for the RPD comprised of military veterans and weapons specialists (put a leaf in this for when I eventually get to Rebecca Chambers). Joining her in STARS are Forest, who she already had a friendship with prior to working together, and Chris. She is the only female officer on STARS Alpha Team, and works as a Breaking and Entering specialist. Forward onto the Mansion Incident.
Again, I’ve mentioned that if given a choice, I will usually not pick Jill to play as. However, that is not to say that I have not played Jill’s scenario in One. My primary complaint about Jill’s Scenario is as follows: It is fundamentally easier than Chris’. She’s got the lockpick set, so she doesn’t need to find Old Keys. She has more inventory space. In the space where she finds the zombie in the bathtub, she stomps his head mid-cutscene and does not have to fight him. She starts with the handgun and receives higher powered weapons whilst Chris has a higher chance of critical headshots. She can mix chemicals to weaken Plant 42 and cut the boss fight in half. Jill can skip certain puzzles in Arklay with Barry’s help, one under the guise of “saving” her from the falling ceiling where you retrieve the shotgun. No need to find the broken shotgun, and you have access to the shotgun as soon as you unlock the area which makes accessing the Armour Key much easier. I used to believe that this was a reflection of the character, but now I believe it is a bit of thinly veiled misogyny on Capcom’s part. ):
About the opening to her scenario, after running amok in the forest and into the mansion - “There are only three STARS members left now. Captain Wesker, Barry, and myself. We don’t know where Chris is.” YOU’VE JUST HAD HIM AT THE DOOR! HOW HAVE YOU LOST HIM? Also, check your maths, Jill. That’s four STARS members. We have one negative point here in that she’s managed to lose her partner in the amount of time it takes to cross a threshold. Anyhow, like how it is when you play as Chris, the other is locked in the cell in the labs and must be released with the MO discs prior to the T-002 battle. Canonically, Jill escapes with Chris and Barry. Chris escapes with Jill and Rebecca. Rebecca does not make an appearance in Jill’s game, nor Barry in Chris’. Brad is there in the background, flying the helicopter he had damned them with at the beginning. It’s a bit of a flub.
Moving on to 3: Nemesis and the Remake and whatever happens in between the events of Arklay and the destruction of Raccoon City. Gathering from memos in Two and Three, shortly after the Arklay Incident, Chris and Jill take their concerns to Chief Irons, requesting the launch of an investigation into Umbrella and all the related shenanigans. Irons, being involved and heavily steeped in wrongdoing, denies this request. STARS all but disbands, as Chris leaves for Europe in August 1998, Barry moves his family to Canada and follows after Chris, Rebecca is doing fuck-all, and Irons has suspended Jill and ordered her confined to her flat. That leaves... Brad Vickers as STARS. The only member. In office. Everyone else is dead, suspended, or AWOL. I suppose one way to operate as a corrupt organisation is to keep the most inept person as your only functioning operative. I digress, this is about Jill and not the bucket of maladroitness that is Brian Irons.
Jill remains in Raccoon City under the pretense of attempting to locate NEST, with the intention of following behind Chris, Barry, and Rebecca(?) a bit later. I believe also she was intending to sort through the rumours of the development of Golgotha, but I cannot find accurate citation of that. Things that she manages to do whilst confined to her flat for a month behind the departure of the other STARS members: Not that at all. I have long wondered what it was that was actually keeping Jill in her flat, aside from orders from her no-longer boss, when she had intentions of leaving on 30 September. I don’t imagine that with what remains of STARS poking around, save for Brad, that Irons would put a definite date on the lifting of her suspension. “Yes, now you may leave to bring down the organisation that I am tangentially working for”. The Three Remake expands on this a bit, as it seems that perhaps Jill was not emotionally nor mentally suited for travel outside of the flat. In which case, I question whether steeping herself in all things Umbrella was perhaps exacerbating her condition. I do believe that there is a fundamentally large difference between Three: Remake Jill and 3: Nemesis Jill. First off, trousers. Enough said. I don’t do my personal investigations sitting in a pleather mini-skirt and a tube top with a rather practical jumper tied around my waist, and neither should you. I much rather imagine a suspension to be carried out in pyjamas, but again I am not the type of person to dress at home if I’m not needed to.
Secondly, Three: Remake Jill holds up much better against Nemesis without the help of Carlos (who is also rather incompetent and sexist), than her original counterpart. Her reactions to goings on are much more believable, and for much of the game she has absolutely no issue putting Carlos within appropriate boundaries. He tries to explain to her what a radio is, she snaps at him. He touches her, she tells him not to. You are a stranger, sir, please observe courtesy. Not to mention, a stranger who is working for the organisation we’ve just found out is responsible for the development of bioweapons and viral agents. At least bother to ask her name, first. A bit of a hint, Carlos: It isn’t “supercop”. If we are to continue on with this Jill further on in the series, I will support it. I would quite enjoy a long-standing female protagonist that has no issue scoffing at male protagonist foolishness and scolding their perspectives. Perhaps it is a good thing that she and Leon have never met in any official capacity.
Three: Remake Jill still falls prey to damsel-syndrome, as I’ll call it, upon being infected by Nemesis. Carlos comes in as the knight in shining armour, having become infatuated with her after knowing her for exactly four hours. I like to imagine that this New Jill could wake up from her comatose state, shout about her autonomy, and then go back to sleep. This is however, remedied by some sort of favour-trading as she does save Carlos in a quid-pro-quo a bit later. I do have concerns about how far Jill allowed Nikolai to get without shooting him down, but that’s unimportant in the long run. There is also a bit of inconsistency between games in how Jill and Carlos escape Raccoon City and what happened just prior, but those are unimportant to our examining of Jill.
All in all, New Jill is portrayed as a competent individual, which I think serves much better to support her character in instances such as the Fall of Umbrella chapter in The Umbrella Chronicles, which leads into the formation of the BSAA and her involvement with them.
Functionally, from 2003 until at least 2009, Chris and Jill mostly function as a singular unit. 2005- they work together to subdue T-ALOS. 2004- The Queen Zenobia, Queen Semiramis fiasco in which Jill carries Parker through a sinking ship as Chris slams doors in her face- as loving partners do. (I do want to mention in an aside that so many people find themselves in trouble whilst looking for Chris. It is the plot of NO FEWER than four games. One, Two, Code: Veronica, and Revelations. Maybe even a bit of Six. Call it four and a half). Revelations does delve into a bit of why I find Jill to be competent amongst the ranks of highly amateur BSAA agents. First off, she reads the manuals for things. She realises the importance of memos! Secondly, she is shown deducing and explaining quite a bit about the situation they find themselves in to Parker, who is often none-the-wiser. An argument could be made that Parker is a newly ported FBC emigre and therefore does not yet have the same expectation but I disagree having seen the... eptitude of other agents. She is rather instrumental in uncovering the whole FBC - Veltro - BSAA mess and quite honestly tends to hold her own in that installment. If only the dodge function worked better. Anyhow, back to her partnership with Chris- it canonically ends with the Lost in Nightmares campaign in Five. In which she quite literally bowls Wesker out of a window in defense of Chris and (sort of) the world.
If there is any secret method of getting me to enjoy a character, it is self-sacrifice for the sake of another. There is something so beautiful about it. Except Ethan, nothing can redeem him. Jill functions best as a character when she is partnered with Chris. I cannot say that in any of these scenarios I have profound issues with her. Forward onto the events of Five and about where we will end this tangent.
Jill and Wesker, obviously, both survive the fall from the Spencer estate. Jill is kept for experimentation due to the existing muted strain of T in her body from the events of Three. The antibodies she possessed were used by Wesker in attempts to make Uroboros more accepting of human host bodies. During the time that she was “in his care” (poor choice of words, I know), he repeatedly injected her with Progenitor strains and took the resulting antibodies. As a result of the testing and antibody removal, Jill’s hair, skin, and eyes lightened in cryostasis (I am still trying to make sense of this bit). Once she had reached the extent of her usefulness, Wesker volunteered her for the P30 project, a Las Plagas extension that utilised chemical compounds for mind control. However, due to the high expulsion rate, the chemical had to be constantly injected, explaining the injector attached to her body.
This requires her, again, rescue at the hands of Chris and Sheva. Once the injector is removed, the other two move on after Wesker, and Jill promptly collapses into unconsciousness. She is found by BSAA Delta Team Captain Josh Stone, who escorts her to a helicopter and initiates a rendezvous with Chris and Sheva on the volcano.
I will stand up for Jill on this one- I do not at all believe that if Jill was on the helicopter, that Sheva should have been the one to wield the rocket launcher. That honour should have belonged to the two original STARS Alpha Team members alone. It’s simply poetic, and I am sorry for Sheva, but it would have been much more perfect.
Currently, we’ve not seen anything from Jill since Five. The only mention to her current condition is that she is at the BSAA undergoing testing and rehabilitation for her time spent with Wesker. In her words: “...ever since getting back I've been locked up in this lab as they run tests on me day in and day out. It's every bit as boring as it sounds”. We leave Jill’s chronology with her being bored. Fitting.
In short, I believe that Jill has quite a bit of potential in her competency, and I am actually quite interested to see what her reaction would be to the BSAA using bioweapons. We’ve not heard from her in twelve years, so one can only assume that she is still alive somewhere, being bored. If they are going to take her character in the same direction they appear to be going in the Three: Remake, I would not at all be adverse to seeing her again in a future standalone installment.
That being said, I have quite the backlog of characters to talk about! Please give me the benefit of the doubt when waiting on these. I’ve got work to do, tea to drink, games to play, and characters to analyse.
Using gene therapy, a research team has succeeded for the first time in getting mice to walk again after a complete cross-sectional injury. The nerve cells produced the curative protein themselves.
To date, paralysis resulting from spinal cord damage has been irreparable. With a new therapeutic approach, scientists from the Department for Cell Physiology at Ruhr-Universität Bochum (RUB) headed by Professor Dietmar Fischer have succeeded for the first time in getting paralyzed mice to walk again. The keys to this are the protein hyper-interleukin-6, which stimulates nerve cells to regenerate, and the way how it is supplied to the animals. The researchers published their report in the journal Nature Communications.
When the communication breaks down
Spinal cord injuries caused by sports or traffic accidents often result in permanent disabilities such as paraplegia. This is caused by damage to nerve fibers, so-called axons, which carry information from the brain to the muscles and back from the skin and muscles. If these fibers are damaged due to injury or illness, this communication is interrupted. Since severed axons in the spinal cord can’t grow back, the patients suffer from paralysis and numbness for life. To date, there are still no treatment options that could restore the lost functions in affected patients.
Designer protein stimulates regeneration
In their search for potential therapeutic approaches, the Bochum team has been working with the protein hyper-interleukin-6. “This is a so-called designer cytokine, which means it doesn’t occur like this in nature and has to be produced using genetic engineering,” explains Dietmar Fischer. His research group already demonstrated in a previous study that hIL-6 can efficiently stimulate the regeneration of nerve cells in the visual system.
In their current study, the Bochum team induced nerve cells of the motor-sensory cortex to produce hyper-Interleukin-6 themselves. For this purpose, they used viruses suitable for gene therapy, which they injected into an easily accessible brain area. There, the viruses deliver the blueprint for the production of the protein to specific nerve cells, so-called motoneurons. Since these cells are also linked via axonal side branches to other nerve cells in other brain areas that are important for movement processes such as walking, the hyper-interleukin-6 was also transported directly to these otherwise difficult to access essential nerve cells and released there in a controlled manner.
Applied in one area, effective in several areas
“Thus, gene therapy treatment of only a few nerve cells stimulated the axonal regeneration of various nerve cells in the brain and several motor tracts in the spinal cord simultaneously,” points out Dietmar Fischer. “Ultimately, this enabled the previously paralyzed animals that received this treatment to start walking after two to three weeks. This came as a great surprise to us at the beginning, as it had never been shown to be possible before after full paraplegia.”
The research team is now investigating to what extent this or similar approaches can be combined with other measures to optimize the administration of hyper-Interleukin-6 further and achieve additional functional improvements. They are also exploring whether hyper-interleukin-6 still has positive effects in mice, even if the injury occurred several weeks previously. “This aspect would be particularly relevant for application in humans,” stresses Fischer. “We are now breaking new scientific ground. These further experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future.”
Let the games begin. To go off on: Mia. To explore changes, potential, concerns, etc: Jill.
Oh! Cooperation is lovely! Thank you, Anonymous! This may be a bit longwinded... We'll give Mia a go first.
My Thoughts on Mia Winters:
I make no secrets that my analysis on Mia will be full of speculation. Quite honestly, though she's been in more games than some of our series protagonists, there isn't much that is truly known about her (Ha, I put "it" and had to correct myself). She is full of mystery, and while that functionally works for Ada and her behind-the-scenes mischief, there is something that absolutely irks me about the enigma that is Mia's purpose.
I think this is why: While Ada ends up being beneficial in some circumstance, Mia finds herself in need of rescuing. We are two for two, at this point. Her presence in both games is inconsequential. Everything that happens involving Mia could have been just as easily expressed in a memo or through cutscenes. Those of you who enjoy her will defend that she did not ask Ethan to come and rescue her in Seven, but truly I am not entirely convinced nor sure of how much of Mia's actions are the E-001 mould or are her own. Therefore, we cannot pick and choose.
We can, however, analyse what Mia was like prior to the E-001 infection.
Let us talk first about the organisation she finds herself involved with. The Connections, founded by Brandon Bailey, who you may recognise from memos in Five- a protégé of Dr. James Marcus. From what I can tell, The Connections does not have much to do with anything other than the E-series. They (he?) attempted partnership with HCF in the early 2000s, but the only bit of information I can find about what they did states that they only managed to "revolutionise" mind-control experiments through the use of fungus. Fungus which they obtained from Miranda under the false pretense that they would use it to resurrect Eva. Right, then- Mia joins them in 2010.
The timeline is a bit wonky in this bit, but stick with me as I try to make some sense of it. Mia and Ethan date in Texas (video games tell me that the most awful things happen in Texas) in the early 2000s, and marry in 2011. Therefore, it is (hopefully) assumed that their relationship was at least somewhat serious prior to Mia joining The Connections in 2010. One would assume that they engaged and Mia celebrated by becoming a bioterrorist. I understand, though. Weddings are expensive.
Mia keeps her job a secret from her to-be, and later- current, husband. She tells him she works as a "worker for a trading company", which- shame on Ethan for not asking more questions to uncover that elaborate ruse. That story falls apart if you brush it with a feather. She even calls the transport and handling of Eveline a "babysitting job" in her video to Ethan at the beginning of Seven. Oh, Ethan, you absolute moron. We should expect that he does suspect something, at least, as in her second video that she attempts to send she states "You're right, I have been lying to you". In October 2014, Mia and Alan spirit Eveline away, intentionally across the Atlantic,
and presumably transporting her to Miranda, because the BSAA uncovered the facility (I am unsure where the facility Eveline was conceived in is located. I assume Texas, as Mia joined The Connections in Texas, and Louisiana is on the way from Texas to Romania). I am aware that some articles state that the Annabelle was headed to Central America, but I cannot find citation of it in a memo, nor remember it in my playthrough of Seven. She is "killed" (fails at containment) whilst "trading goods" (smuggling a sentient bioweapon). Ethan presumably moves on with his life, all the better for no longer having Mia as a spouse. ... Until July, 2017. All bad things happen in July in this series. Arklay, Lanshiang, now this.
As we cannot be certain that Mia is not lying, due to her track record, I will state that we cannot be sure that she did not lure Ethan to Dulvey, and therefore is entirely involved in the events of Seven, from transport to finality. Mia, canonically, unfortunately, is "cured" with the serum and evacuated from the Dulvey Estate by Blue Umbrella (which I take absolute issue with).
I've said this timeline is a mess, and my thoughts are equally messy, so I apologise again. We'll move on to Village and the bulk of what I suspect is Mia's covert (if you could call it covert) allied relationship with Miranda. Previous to October 2014, Miranda travelled to The Connections facility that was housing Eveline. There, she met and conversed with both Mia and Alan. Both were working in tandem for and with The Connections, and both were intimately involved in the E-series.
Back to the whole transporting Eveline across the ocean bit, because I've just had a thought, just WHO approves of transporting a BOW of Eveline's calibre without containment measures and protocols? Oh, yes, it could not possibly backfire that we've given everyone out of the know the impression that this is a family with a not-at-all-dangerous small child. Yes, a gun will fix it. Perfect. Whose idea was this? Mia? Alan? Brandon? Whomever, you're thick.
Anyhow- I wholly and fully believe that Mia's involvement in Village and, by proxy, with Miranda, is willful. They had met before, and by extension had worked together, on the E-series project in specific regard to Eveline and the moulded. Rosemary is born to Mia and Ethan, and the BSAA relocates the Winterses (this still makes me laugh as it does not, at all, roll off the tongue) to Romania. I am not one hundred percent certain how this comes to be the location, as I have faith that Mia would know that Miranda operates nearby. There is too much happenstance for it to not be purposeful. That, however, involves Chris in some fashion and I cannot make that connection in a way that I enjoy it. I like to imagine that Mia simply expressed that she had always wanted to visit Romania, and the BSAA bungled it accordingly.
A bit more on the BSAA in this whole instance:
While I do find them entirely insufferable, an utter joke at times, I do believe that some of them are at least somewhat competent. Yes, even Miss Valentine. Canonically, The Connections has a mole in the BSAA. The Connections, who hired Lucas Baker as Head Researcher in the E-series project. The Connections, who trusted Mia to transport a sentient BOW without containment measures. Has a mole. In the BSAA.
Sure.
Anyhow, this "mole" provides Miranda with intel of where the Winterses are living, that they've just had a baby, that both Mia and Ethan are living fungal colonies, and therefore, perhaps, maybe, Rosemary may be a suitable substitute for Eva. Bit of a leap of logic there, but I digress.
This "mole" in the BSAA must absolutely be Mia. I do not think so much it's that she's in the BSAA so much as that she is privy to whatever intel they would have regarding her family because she is a part of it. Again, she would have know they were close to Miranda. "Remember that mouldy pseudo-child BOW that my organisation promised you? Have I got news for you- my husband and I have gone stale, I've got a daughter, and I'm right in the neighbourhood!"
It ultimately makes more sense in the whole of how the universe operates that Mia and Miranda would be in league with one another. One does not simply make connections in... Well, The Connections... For all this to be coincidence.
Miranda takes Mia's forme and then goes on to impersonate Mia for days, her confrontational attitude goes unnoticed by Ethan because Mia's mould-type is of the toxic variety. Allegedly, Mia is captured and holed up in Miranda's lab having been experimented on. The only supporting evidence to Mia having been experimented on is in Eugen's Diary, stating that Miranda asked Eugen to bring her medical equipment and drugs on Wednesday, 3 February 2021. On Friday, 5 February, Miranda had taken Mia's place. And, of course, Mia's claim that she was experimented on and held hostage. I have one question of all of this:
Why would Miranda need to experiment on Mia if she is infected with the same E-series mould that Miranda already has samples and an unlimited supply of due to her proximity to the megamycete? Mia does not state that she is special after being rescued by Chris, only that Ethan is special. I would argue that both are rather run-of-the-mill, but again, I digress. Simply put, I don't believe that she would need to. Us scientists are not in the habit of wanting to perform experiments for the sake of using up supplies.
Furthermore, when Chris finds Mia in Miranda's lab, she is "imprisoned" in oddly the same way as she was in Seven. Behind bars, but unrestrained. In Village, Mia even has relative access to a weapon which she tries to attack Chris with. While Miranda is a mimic, after having obtained target DNA, I do not imagine that it would be easy to have mistaken Chris for Miranda. Unless Miranda regularly comes down to her lab as other people, which would be rather amusing- though setting up for a massive security issue.
If you were to imprison someone for experimentation, it's likely you wouldn't give them anything they could possibly use to attack you with. At least, that's how I would do it in the off chance that for whatever reason I became interested in imprisoning someone against their will for the purpose of science. (Do not read into this, Christiana.)
I believe that Mia intended to attack Chris, and after failing miserably, played the damsel card.
I will end this rambling on this note: She is entirely rude, confrontational, and hostile for someone who has just been rescued from imprisonment and had their baby saved. Honestly, if this is her default personality, who could fault Ethan for not noticing his wife being replaced for three days?
In short: Ethan should have saved Zoe instead. Mia Winters is a false-protagonist who has found herself in more than a few suspicious situations, has proven from the beginning to be a liar, and already has the connection with Miranda that might foster her involvement in the events of Seven and Village.
I'm certain I've missed something further that would be worth discussing. We will cover Jill in another entry as this has run much too long already, and it is time for my job as a worker at a trading company.
Nasal spray delivers antipsychotic drugs straight to the brain, cutting required dose by up to 75 per cent and reducing adverse side effects
A team of neuroscientists and engineers at McMaster University has created a nasal spray to deliver antipsychotic medication directly to the brain instead of having it pass through the body.
The leap in efficiency means patients with schizophrenia, bipolar disorder and other conditions could see their doses of powerful antipsychotic medications cut by as much as three quarters, which is expected to spare them from sometimes-debilitating side effects while also significantly reducing the frequency of required treatment.
The new method delivers medication in a spray that reaches the brain directly through the nose, offering patients greater ease of use and the promise of improved quality of life, including more reliable, effective treatment.
Ram Mishra, a professor in the Department of Psychiatry and Behavioural Neurosciences and co-director of McMaster’s School of Biomedical Engineering, and Todd Hoare, a Canada Research Chair and professor of chemical engineering, describe their research in a newly published article in the Journal of Controlled Release.
They and their co-authors Michael Majcher, Ali Babar, Andrew Lofts, and Fahed Abuhijleh have proven the concept of their new delivery mechanism in rats with PAOPA, an experimental drug used to treat schizophrenia. In related work, the researchers have also produced similar results with other, commonly prescribed antipsychotic drugs.
A problem for patients using antipsychotic medications, Mishra explains, is that taking them orally or by injection means the drugs must pass through the body before they reach the brain through the blood. To be sure enough oral or injected medication reaches the brain, a patient must take much more than the brain will ultimately receive, leading to sometimes serious adverse side effects, including weight gain, diabetes, drug-induced movement disorders and organ damage over the long term.
When delivered through the nose, the spray medication can enter the brain directly via the olfactory nerve.
“The trick here is to administer the drug through the back door to the brain, since the front door is sealed so tightly,” Mishra says. “This way we can bypass the blood-brain barrier. By delivering the drug directly to the target, we can avoid side effects below the brain.”
Mishra and collaborator Rodney Johnson of the University of Minnesota had previously created a water-soluble form of the medication, which was used in the current research. The new form they created was easier to manipulate, but they still lacked an effective vehicle for getting it to the brain. A particular issue was that drugs delivered via the nose are typically cleared from the body quickly, requiring frequent re-administration.
Hoare, in the meantime, had been working with an industrial partner to develop the use microscopic nanoparticles of corn starch for agricultural applications.
The two scientists, who work across campus from one another, came together after researchers in their labs met at an internal McMaster conference. Two of the researchers, Babar and Lofts, worked on the project in both labs.
The engineering team was able to bind the drug to the corn starch nanoparticles that, when sprayed together with a natural polymer derived from crabs, could penetrate deep into the nasal cavity and form a thin gel in the mucus lining, slowly releasing a controlled dose of the drug, which remains effective for treating schizophrenia symptoms over three days.
“The cornstarch nanoparticles we were using for an industrial application were the perfect vehicle,” Hoare says. “They are naturally derived, they break down over time into simple sugars, and we need to do very little chemistry on them to make this technology work, so they are great candidates for biological uses like this.”
The gradual release means patients would only need to take their medication every few days instead of every day or, in some cases, every few hours.
Scientists jump-start two people’s brains after coma
In 2016, a team led by UCLA’s Martin Monti reported that a 25-year-old man recovering from a coma had made remarkable progress following a treatment to jump-start his brain using ultrasound.
Wired U.K. called the news one of the best things that happened in 2016. At the time, Monti acknowledged that although he was encouraged by the outcome, it was possible the scientists had gotten a little lucky.
Now, Monti and colleagues report that two more patients with severe brain injuries — both had been in what scientists call a long-term “minimally conscious state” — have made impressive progress thanks to the same technique. The results were published online in the journal Brain Stimulation.
“I consider this new result much more significant because these chronic patients were much less likely to recover spontaneously than the acute patient we treated in 2016 — and any recovery typically occurs slowly over several months and more typically years, not over days and weeks, as we show,” said Monti, a UCLA professor of psychology and neurosurgery and co-senior author of the new paper. “It’s very unlikely that our findings are simply due to spontaneous recovery.”
The paper notes that, of three people who received the treatment, one — a 58-year-old man who had been in a car accident five-and-a-half years prior to treatment and was minimally conscious — did not benefit. However, the other two did.
One is a 56-year-old man who had suffered a stroke and had been in a minimally conscious state, unable to communicate, for more than 14 months. After the first of two treatments, he demonstrated, for the first time, the ability to consistently respond to two distinct commands — the ability to drop or grasp a ball, and the ability to look toward separate photographs of two of his relatives when their names were mentioned.
He also could nod or shake his head to indicate “yes” or “no” when asked questions such as “Is X your name?” and “Is Y your wife’s name?”
Small but significant improvement
In the days following the second treatment, he also demonstrated, for the first time since the stroke, the ability to use a pen on paper and to raise a bottle to his mouth, as well as to communicate and answer questions.
“Importantly,” Monti said, “these behaviors are diagnostic markers of emergence from a disorder of consciousness.”
The other patient who improved is a 50-year-old woman who had been in even less of a conscious state for more than two-and-a-half years following cardiac arrest. In the days after the first treatment, she was able, for the first time in years, according to her family, to recognize a pencil, a comb and other objects.
Both patients showed the ability to understand speech.
“What is remarkable is that both exhibited meaningful responses within just a few days of the intervention,” Monti said. “This is what we hoped for, but it is stunning to see it with your own eyes. Seeing two of our three patients who had been in a chronic condition improve very significantly within days of the treatment is an extremely promising result.”
The changes the researchers saw are small, but Monti said even the smallest form of communication means a way to reconnect. One powerful moment during the study was when the wife of the 56-year-old man showed him photos and asked whether he recognized who he saw.
“She said to us, ‘This is the first conversation I had with him since the accident,’” Monti said. “For these patients, the smallest step can be very meaningful — for them and their families. To them it means the world.”
Using acoustic energy
The scientists used a technique called low-intensity focused ultrasound, which uses sonic stimulation to excite the neurons in the thalamus, an egg-shaped structure that serves as the brain’s central hub for processing. After a coma, thalamus function is typically weakened, Monti said.
Doctors use a device about the size of a saucer creates a small sphere of acoustic energy they can aim at different brain regions to excite brain tissue. The researchers placed the device by the side of each patient’s head and activated it 10 times for 30 seconds each in a 10-minute period. Each patient underwent two sessions, one week apart.
Monti hopes to eventually translate the technology into an inexpensive, portable device so the treatment could be delivered not only at state-of-the-art medical centers, but also at patients’ homes, to help “wake up” patients from a minimally conscious or vegetative state.
The treatment appears to be well tolerated; the researchers saw no changes to the patients’ blood pressure, heart rate or blood oxygen levels, and no other adverse events. Monti said the device is safe because it emits only a small amount of energy, less than a conventional Doppler ultrasound.
While the scientists are excited by the results, they emphasize that the technique is still experimental and likely will not be available to the public for at least a few years. For now, there is little that can be done to help patients recover from a severe brain injury that results in either a chronic vegetative state or a minimally conscious state, Monti said.
Monti said his team is planning additional studies to learn exactly how thalamic ultrasound modifies brain function; he hopes to start those clinical trials once the researchers and patients are assured of being safe from COVID-19.
