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Poetry of Neurology

We are more than our neurons or their combinations, co-relations, conjunctions, functions and interactions, that are conducted through their gap junctions, synapses or action potentials. We are more than the cells, tissues, organs, systems, DNAs, RNAs, genes etc and their ultimate unification into a whole mechanism and system of magnificence. We are an infinity unfolding itself in the name of the human mind which, through the physiology of what on appearance is a human physique, it becomes, dreams, imagines, creates, loves and does human: the most astonishing of all things, that we find on this Universe. All we have to do is to look at its unity off the billion plus expressions of its self and wonder about its endless expressive diversity off the same self in billion plus instances to realise that this human mind is magnificent a thing for the purpose of which the neurology is given to it as the most sophisticated, most elaborately engineered, most complexity-strewn an architecture, a most awe-inspiring bio-chemico-genetico-mechanism, that we humans will ever see in this Universe; nothing else will ever surpass this magnificence.
















And it all begins with the book of genome, that has already been written, that will have all the tools to keep on writing the future of a human physiology and with that begins the human life and soon the Cardiology is formed and follows neurology: the duo or the two in one or the one in two: for they, neither ends nor begins alone but, rather, both just clasp, grasp, sew, knit, cut, run, crisscross, bind, bend, blend and flow in, out, between and through the human physiology in such an 'infinity of subtle, intricate and sublime artistry', that the entire creation of this Universe does not have a parallel to show next to it. And with this Cardiology and Neurology the human becomes more than a physiology: it becomes a human mind and that has not been written out, unlike the genome, which has been, and, here is, where the entire life of this human mind is, as if it has got infinity of white papers bundled into a beautiful blank book, that no one can know how to write but that human mind alone does and this is where humanity is, this is what humanity is and this is how humanity is and this why we publish The Humanion to write a Beautiful Book out of those blank white pages of that book, where genome alone can never write a single word unless The Sanctum Mayakardium and The High Neuranium join forces to make 'one': the one, that is exactly like the heart with two atria; or the one, that is exactly like the brain with two hemispheres: it is two in one and one in two. And here is to this awe, to Humanity

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A Type of Cerebral Haemorrhage Considered Rare Cause More Deaths Among Middle-Aged Women Than Other Strokes




|| Sunday: November 15: 2020 || ά. According to a recently published Finnish Study, subarachnoid haemorrhage:SAH, which has so far been considered a relatively rare type of stroke, causes a significant share of all fatalities among middle-aged people. The number of, in particular, middle-aged women, whose death is caused by subarachnoid haemorrhage is higher than the corresponding figure for cerebral infarction, a much more common disorder measured by the number of cases for all ages.

SAH, the most fatal of all cerebrovascular disturbances, results in death for 40-50% of patients, suffering from the condition in the first months after the haemorrhage. The annual incidence of SAH is considered to be six to seven cases per 100,000 people globally. Due to its rarity, the effects of this cerebral haemorrhage type have been considered very minor on the population level. Furthermore, it has been previously estimated that no more than 04% of all deaths caused by strokes are caused by SAH.

Although, the disease has been known to be most prevalent among the middle-aged population, it has been impossible to reliably determine the share of deaths among the working-age population, caused by subarachnoid haemorrhage: As many as a quarter of SAH patients die before reaching the hospital and many countries record the deaths of such SAH patients according to more likely causes, for example, as sudden cardiac deaths. If, an autopsy is not conducted in the case of sudden death, the cause of death and the possibility of SAH remain undetermined.

In Finland, autopsies are mandated by law to be conducted to determine the cause of death in cases of sudden death. This has enabled Finnish researchers to determine, for the first time, the share of deaths caused by subarachnoid haemorrhage in all deaths of middle-aged people. The registry Study, which was recently published in the Journal of Neurology, Neurosurgery and Psychiatry:JNNP, included precise details on the cause of death for, almost, 200,000 individuals between the ages of 40 and 65, who have died in Finland in the past 20 years.

The results indicate that, in middle-aged women, subarachnoid haemorrhage was the 12th most common cause of death from among all deaths and the most common type of stroke death throughout the entire 20-year study period. According to Dr Ilari Rautalin, the Principal Investigator, the finding is a surprise in the light of previous literature.

“In middle-aged women in particular, the number of SAH deaths clearly exceeds that of deaths, caused by cerebral infarctions, deaths from several cancers and, for example, car crashes and other accidents.” says Mr Rautalin, Bachelor of Medicine, who is, also, a PhD student.

As SAH is a disease, primarily caused by smoking and high blood pressure, it is largely preventable. “Investment in healthy lifestyles would cut down significantly the share of premature deaths among the working-age population.” says Dr Rautalin. The other two members of the research group and authors of the article, Dr Miikka Korja, Docent and Neurosurgeon at Helsinki University Hospital and Professor Jaakko Kaprio, Professor of Genetic Epidemiology at the University of Helsinki, also, emphasise the importance of a healthy lifestyle.

According to them, premature deaths among the working-age population could be effectively prevented, for example, by encouraging people to not smoke and by preventing hypertension, as well as, by providing them with good care. TheSstudy of deaths among Finnish middle-aged people is based on population-level registers, maintained by Statistics Finland and the Finnish Institute for Health and Welfare. The registers make it possible to carry out comprehensive studies on subarachnoid haemorrhage in Finland.

“There have been digital health registers in use in Finland from the 1960s. Finland’s high-quality healthcare system and a number of related top-level registers, that cover the entire population are the reason why Finland has produced so many ground-breaking studies on subarachnoid haemorrhage.” says Docent Korja, who heads the group. Recently, the group published a finding on the effect of smoking on subarachnoid haemorrhage and they have now uncovered new information on the share of SAH deaths among middle-aged people. However, the significance of several risk factors, potentially, associated with SAH remains unknown.

“The topic is in urgent need of high-quality research evidence based on the health records of hundreds of thousands of individuals and decades-long monitoring periods.” Dr Rautalin says.

The Paper: Burden of aneurysmal subarachnoid hemorrhage deaths in middle-aged people is relatively high : Rautalin I, Kaprio J, Korja M:. JNNP, 2020. DOI: 10.1136/jnnp-2020-324706

Further information: Ilari Rautalin, Bachelor of Medicine, doctoral student, University of Helsinki: Phone: +358 40 525 7709: Email: ilari.rautalin

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The First UK-wide Study of Brain Complications in Patients With COVID-19


|| Monday: June 29: 2020 || ά. Researchers from the University of Southampton are amongst a UK team of scientists to conduct the first nationwide surveillance study of the neurological complications of COVID-19. A Study of 153 patients, treated in UK hospitals during the acute phase of the COVID-19 pandemic describes a range of neurological and psychiatric complications, that, may be, linked to the disease, including, stroke and an altered mental state, such as, brain inflammation, psychosis and dementia-like symptoms.

The findings are published in The Lancet Psychiatry and provide valuable and timely information, urgently needed by clinicians, researchers and funders to inform the next steps in neuroscience COVID-19 research and health policy planning. Increasingly, concerns regarding potential neurological complications of COVID-19 are being reported. However, most published reports have been limited to individual cases or small case series and, even, larger studies have been limited by both geography and specialty. Consequently, many important questions remain, such as, how common complications are, whether novel syndromes are emerging and which people are most at risk.

To address this, the CoroNerve Studies Group, a collaboration between the universities of Liverpool, Southampton, Newcastle and UCL, developed a rapid notification case identification system across the spectrum of major UK Neuro-science Professional Bodies, representing neurology, stroke, psychiatry and intensive care.

During three weeks of the exponential pandemic phase, the researchers identified 153 cases from across the UK, who had both a new COVID-19 diagnosis and a new neurological or psychiatric diagnosis, requiring hospital admission, including, those admitted to intensive care and or recovering from critical illness.

The median age of the patients was 71, 23-94, years. Of the 125 patients for whom complete clinical data was available, 57, 44%, suffered ischemic strokes and 39, 31%, experienced an altered mental state reflecting both neurological and psychiatric diagnoses. Whereas 61, 82%, cases of cerebro-vascular events occurred in those over 60 years old, half of cases with an altered mental state were under 60 years old.

The Southampton research team, led by Dr Aravinthan Varatharaj and Dr Ian Galea, from the Southampton Clinical and Experimental Neurology Team, use this data to investigate causality and identify risk factors for neurological involvement during COVID-19. Dr Galea, Associate Professor and Senior Author, leading the Study for Southampton, said, “The University of Southampton played a key role in establishing the UK-wide surveillance system CoroNerve to monitor serious effects of COVID-19 on the nervous system.

The project continues with the next phase, during which the University’s world-leading Clinical Informatics Research Unit, are playing an essential role to help researchers identify risk factors for early identification of neurological involvement and effective treatment strategies.”

Dr Benedict Michael, who led the Study for the University of Liverpool, said, “Whilst an altered mental state was being reported by some clinicians, we were surprised to identify quite so many cases, particularly, in younger patients and by the breadth of clinical syndromes, ranging from brain inflammation, encephalitis, through to psychosis and catatonia.

Clinicians should be alert to the possibility of patients with COVID-19, developing these complications and, conversely, of the possibility of COVID-19 in patients, presenting with acute neurological and psychiatric syndromes.”

It is not possible to draw conclusions about the total proportion of COVID-19 patients likely to be affected based on this Study. Larger studies are now needed to identify the broader cohort of COVID-19 patients both in and outside of hospitals, to determine clearer estimates of the prevalence of these complications, those at risk, and impact on recovery.

Co-author Professor Tom Solomon, Director of the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool, said, “This Study provides a great snapshot of the spectrum of COVID-19 associated neurological disease in the UK. Now we can recognise these problems, we need to understand in more detail why some patients are developing these complications and what we can do to stop it. It will, also, be interesting to see how these data compare with other countries.”

The CoroNerve Studies Group is supported by the Association of British Neurologists, Royal College of Psychiatrists, British Association of Stroke Physicians, British Paediatric Neurology Association, NeuroAnaesthesia and Critical Care Society, Intensive Care Society, Faculty of Intensive Care Medicine and the Encephalitis Society.

The researchers are supported by grants from the Medical Research Council, Wellcome, National Institute of Health Research and Academy of Medical Sciences.

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Cell Pores Discovery Gives Hope to Millions of Brain and Spinal Cord Injury Patients



|| Tuesday: June 16: 2020 || ά. Scientists have discovered a new treatment to dramatically reduce swelling after brain and spinal cord injuries, offering hope to 75 million victims worldwide each year. The breakthrough in treating such injuries, referred to as, central nervous system:CNS edema, is thought to be hugely significant because current options are limited to putting patients in an induced coma or performing risky surgery.

Brain and spinal cord injuries affect all age groups. Older people are more at risk of sustaining them from strokes or falls, while for younger age groups, major causes include road traffic accidents and injuries from sports, such as, rugby, US-style football and other contact games. The high-profile example of Formula One racing driver Mr Michael Schumacher, demonstrates the difficulties physicians currently face in treating such injuries. After falling and hitting his head on a rock while skiing in Switzerland in 2013, Mr Schumacher developed a swelling on his brain from water rushing into the affected cells.

He spent six months in a medically-induced coma and underwent complex surgery but, his rehabilitation continues to this day. The new treatment, developed by an international team of scientists, working at the Aston University, UK, Harvard Medical School, US, University of Birmingham, UK, University of Calgary, Canada, Lund University, Sweden, Copenhagen University, Denmark and University of Wolverhampton, UK, features in the latest edition of the scientific journal Cell.

The researchers used an already-licensed anti-psychotic medicine, Trifluoperazine:TFP, to alter the behaviour of tiny water channel ‘pores’ in cells, known as, aquaporins. Testing the treatment on injured rats, they found those animals, given a single dose of the drug at the trauma site recovered full movement and sensitivity in as little as two weeks, compared to an untreated group, that continued to show motor and sensory impairment beyond six weeks after the injury.

The treatment works by counteracting the cells’ normal reaction to a loss of oxygen in the CNS, the brain and spinal cord, caused by trauma. Under such conditions, cells quickly become ‘saltier’ because of a build-up of ions, causing a rush of water through the aquaporins, which makes the cells swell and exerts pressure on the skull and spine. This build-up of pressure damages fragile brain and spinal cord tissues, disrupting the flow of electrical signals from the brain to the body and vice versa. 

But the scientists discovered that TFP can stop this from happening. Focusing their efforts on important star-shaped brain and spinal cord cells, called, astrocytes, they found TFP prevents a protein, called, calmodulin from binding with the aquaporins. Normally, this binding effect sends the aquaporins shooting to the surface of the cell, letting in more water. By halting this action, the permeability of the cells is reduced.

Traditionally, TFP has been used to treat patients with Schizophrenia and other mental health conditions. Its long-term use is associated with adverse side effects but, the researchers said that their experiments suggested that just a single dose could have a significant long-lasting impact for CNS Edema patients.

Since TFP is already licensed for use in humans by the US Federal Drug Administration:FDA and UK National Institute for Health and Care Excellence:NICE, it could be rapidly deployed as a treatment for brain injuries. But the researchers stressed that further work would allow them to develop new, even, better medicines, based on their understanding of TFP’s properties.

According to the World Health Organisation:WHO, each year around 60 million people sustain a traumatic brain or spinal cord injury and a further 15 million people suffer a stroke. These injuries can be fatal or lead to long-term disability, psychiatric disorders, substance abuse or self-harm.

Professor Roslyn Bill of the Bio-sciences Research Group at Aston University said, “Every year, millions of people of all ages suffer brain and spinal injuries, whether from falls, accidents, road traffic collisions, sports injuries or stroke. To date, their treatment options have been very limited and, in many cases, very risky.

This discovery, based on a new understanding of how our cells work at the molecular level, gives injury victims and their doctors hope. By using a drug already licensed for human use, we have shown how it is possible to stop the swelling and pressure build-up in the CNS, that is responsible for long-term harm. While further research will help us to refine our understanding, the exciting thing is that doctors could soon have an effective, non-invasive way of helping brain and spinal cord injury patients at their disposal.”

Dr Zubair Ahmed of the University of Birmingham’s Institute of Inflammation and Ageing, said, “This is a significant advance from current therapies, which only treat the symptoms of brain and spinal injuries but do nothing to prevent the neurological deficits, that, usually, occur as a result of swelling. The re-purposed drug offers a real solution to these patients and can be fast-tracked to the clinic.”

Dr Alex Conner of the University of Birmingham’s Institute of Clinical Sciences,  said, “It is amazing that our work, studying tiny water channels in the brain can tell us something about traumatic brain swelling, that affects millions of people every year.”

Dr Mootaz Salman, Research Fellow in Cell Biology at Harvard Medical School, said, “This novel treatment offers new hope for patients with CNS injuries and has huge therapeutic potential. Our findings suggest it could be ready for clinical application at a low cost in the very near future.”

Dr Matthew Conner, the Course Director for Biochemistry and Genetics and Molecular Biology at the University of Wolverhampton, said, “Our breakthrough research offers new hope for the treatment and prevention of brain damage in people with head injuries. This cutting-edge work is the culmination of a number of years of collaborative research on the behaviour of the tiny water channel ‘pores’ in cells known as aquaporins.”

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New Study Finds: Former Professional Footballers Had an Approximately Three and a Half Times Higher Rate of Death Due to Neuro-degenerative Disease Than Expected




|| Monday: October 21: 2019: University of Glasgow News || ά. A new Study, led by the University of Glasgow, has shown the first major insights into lifelong health outcomes in former professional footballers. The findings of the Study have been published today in The New England Journal of Medicine.

In the Study, funded by the Football Association:FA and the Professional Footballers’ Association:PFA, the researchers compared the causes of death of 7,676 former Scottish male professional football players, who were born between 1900 and 1976 against those of more than 23,000 matched individuals from the general population.

Led by Dr Willie Stewart, Consultant Neuro-pathologist, who is an honorary Clinical Associate Professor at the University of Glasgow, the FIELD Study found that former professional footballers had an approximately three and a half times higher rate of death due to neuro-degenerative disease than expected.

Dr Stewart, said, “This is the largest Study to date, looking in this detail at the incidence of neuro-degenerative disease in any sport, not just professional footballers. A strength of our study design is that we could look in detail at rates of different neuro-degenerative disease sub-types.

This analysis revealed that risk ranged from a five-fold increase in Alzheimer’s Disease, through an approximately four-fold increase in Motor Neurone Disease, to a two-fold Parkinson’s Disease in former professional footballers, compared to population controls.”

Although, footballers had higher risk of death from neuro-degenerative disease, they were less likely to die of other common diseases, such as, heart disease and some cancers, including, Lung Cancer. Reflecting these findings, the Study found that deaths in former footballers were lower than expected up to age 70 and higher than expected over that age.

Dr Stewart said, “An important aspect of this work has been the ability to look across a range of health outcomes in former professional footballers. This allows us to build a more complete picture of health in this population.

Our data show that, while former footballers had higher dementia rates, they had lower rates of death due to other major diseases. As such, whilst every effort must be made to identify the factors contributing to the increased risk of neuro-degenerative disease to allow this risk to be reduced, there are, also, wider potential health benefits of playing football to be considered.”

The association between contact sport participation and neuro-degenerative disease has been subject to debate in recent years. Post-mortem studies have identified a specific dementia pathology, linked to exposure to brain injury, known as, Chronic Traumatic Encephalopathy:CTE, in a high proportion of brains of former contact sports athletes, including, former footballers in parallel studies led by Dr Stewart.

However, until this Study, it was not clear whether there was any evidence of an increase in neuro-degenerative disease rate in former footballers. Mr Greg Clarke, FA Chairman, said, "This is the most comprehensive Study ever commissioned into neuro-degenerative disease in former professional footballers. We welcome its findings and thank Dr Willie Stewart for diligently leading this important research.

The whole game must recognise that this is only the start of our understanding and there are many questions, that still need to be answered. It is important that the global football family now unites to find the answers and provide a greater understanding of this complex issue. The FA is committed to doing all it can to make that happen."

Mr Gordon Taylor, PFA Chief Executive, said, “These findings are a matter of considerable importance to our members. We are grateful to Dr Willie Stewart and his team for their work.

The PFA co-funded FIELD, alongside the FA. It is now incumbent on football globally to come together to address this issue in a comprehensive and united manner. Research must continue to answer more specific questions about what needs to be done to identify and reduce risk factors.

Our members; well-being is of paramount importance to us and we are committed to representing their voice as this conversation opens up across football’s stakeholders.”

The Paper: Neurodegenerative disease mortality in former professional soccer players: Published in The New England Journal of Medicine.


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New Study Finds: Cannabidiol or CBD Reduces the Impairments of Brain Functions Caused by Cannabis



|| Sunday: April 28: 2019: UCL News || ά. The more cannabidiol:CBD in a strain of cannabis, the lower the impairment to brain function, according to a new UCL-led brain imaging Study. The Research, published in the Journal of Psychopharmacology, is the first Study, using functional magnetic resonance imaging:fMRI to gauge how different strains of cannabis impact brain function.  “Over the last two decades, rates of addiction and psychosis, linked to cannabis, have been on the rise, while at the same time, stronger strains of cannabis with more THC and less CBD have become increasingly common.” said the Study’s Lead Author, Dr Matt Wall, UCL Clinical Psychopharmacology Unit and Invicro.

“We have now found that CBD appears to buffer the user against some of the acute effects of THC on the brain.” There is growing evidence that THC is implicated in addiction and cannabis-induced psychosis. CBD, on the other hand, is being researched for a range of therapeutic functions but, the interplay between THC and CBD is not yet well-known. In the present Study, the researchers monitored brain activity at rest in 17 people after taking different strains of cannabis. The two strains have equal levels of tetrahydrocannabinol:THC but, one of them, also, has high levels of CBD while the other strain, a high-strength cannabis, commonly, known as, skunk, contained negligible levels of CBD.

Both strains are comparable to the different strains of cannabis in common usage. The researchers found that the low-CBD strain impaired functional connectivity in the brain’s default mode, particularly, in the posterior cingulate area and salience networks, while the high-CBD strain caused only a minimal disruption to these regions, suggesting that the CBD counteracts some of THC’s harmful effects.

The salience network supports other brain networks and determines what sensory or emotional inputs we pay attention to and disruptions of the network have, previously, been implicated in addiction and psychosis.

The researchers, also, found that the THC-induced disruption of functional connectivity in the posterior cingulate was strongly correlated with participants’ reports of subjective experiences, such as, feeling more ‘stoned’ or ‘high’, suggesting that the brain area, may be, central to driving cannabis’ subjective effects. This relationship between the posterior cingulate and subjective effects was, also, blocked by CBD.

The researchers say that their findings add to evidence that cannabis strains with greater CBD content, may be, less harmful, suggesting that CBD content of cannabis should perhaps be regulated in jurisdictions where it’s legal. “As cannabis is becoming legal in more parts of the world, people buying cannabis should be able to make an informed decision about their choice of cannabis strain and be aware of the relative risks.” said Dr Wall.

The findings, also, provide insight into why CBD holds potential for medicinal uses.  “If, CBD can restore disruption to the salience network, this could be a neuro-protective mechanism to explain its potential to treat disorders of salience, such as, psychosis and addiction.” said Senior Author Professor Val Curran, UCL Clinical Psychopharmacology Unit.

The Study involved researchers at UCL, Invicro, King’s College London, Imperial College London and the University of Bath and was supported by Drug Science, Channel 4 Television and the Beckley Foundation.:::ω.

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New Research Finds: Background Noise Strongly Impairs Children’s Ability to Concentrate




|| February 25: 2019: Aalto University News: Tiina Aulanko-Jokirinne Writing || ά. A new brain-imaging Study compared the cocktail party effect between adults and children. The Study sought to understand how children cope the often noisy surroundings, in which, they grow and learn. Neuro-scientists of Aalto University in Finland and Erasme Hospital in Belgium compared brain activities of adults and children during the so-called ‘cocktail party effect,’ that is the ability to pay attention to a single speaker in a noisy environment.

Compared with adults, the children's brain activity followed less reliably the speaker's voice, especially, when the background noise was high. “Children’s ability to concentrate on their teacher is disrupted in a noisy environment, such as, in a noisy class room and this, may, affect their learning.’’ says Mr Veikko Jousmäki, a Senior Researcher at the University. Published in the Journal of Neuro-science, the Study compared adults with children, aged six to nine years. The researchers used magneto-encephalography:MEG to follow the brain activity while the subjects were asked to focus on one speaker’s voice in the background noise.

The background noise consisted of the other speakers’ stories and the noise level was modified in different sessions. Without any background noise, the brain accurately tracked the speech stream in both adults and children. When the level of background noise was increased, adults' brains were still able to follow the intended speaker but, children lost this focus rather quickly.

The results imply that the ability to concentrate in a noisy environment develops with age. School children are not yet able to easily pick up the intended speech stream in background noise. The brain recordings agree with previous findings showing that children have difficulties in understanding speech in noisy surroundings.

“Brain recordings allowed us to see how the listener’s auditory cortex was driven by the listened speech stream. When the level of background noise increased, adults’ brains still continued to track the intended speaker’s voice as a coherent stream, whereas children easily lost this focus.” says Mr Jousmäki.

This study is a part of a larger series of experiments, that were started by developing a coherence-based method to follow the relationship between brain signals and the listened natural speech. The same Finnish–Belgian research team demonstrated in 2013 how the right-hemisphere auditory cortex reacts to different rhythms of speech. More recently, this analysis method has been applied to the study of people suffering from autism-spectrum disorders.

“Our next goal is to find out how children could be helped to cope with the often noisy growth and learning environments.” says Mr Jousmäki.

Further information: Veikko Jousmäki: Senior Scientist: Aalto University: email: veikko.jousmaki at tele: +358 400 952 525

The Paper: Cortical tracking of speech-in-noise develops from childhood to adulthood:::ω.

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A Survey of Contemporary Brain Research Approaches and the Challenges for the Research Communities Seeking to Cure Brain Cancer




|| February 22: 2019: Institute of Cancer Research News: Conor McKeever Writing || ά. Researchers and clinicians from across the world, including, the Chief Executive of the Institute of Cancer Research, Professor Paul Workman and Professor Raj Chopra and Professor Louis Chesler, have come together to set out how future research can finally deliver major progress against brain cancer in both adults and children. Despite many years of excellent research to improve our scientific understanding of cancer and great progress in improving the survival of many types, brain tumours have remained a particularly tough nut to crack.

Only 14 per cent of patients with brain cancer survive for five or more years after being diagnosed, a number, that has improved little over the last 40 years. A key reason for this is that we’re simply not discovering and developing enough innovative new treatments for brain cancers. Indeed, here at the Institute of Cancer Research we released a major Report on drug access in December, which found, among other things, that no new brain cancer drugs at all were licensed by the European Medicines Agency between the years 2000 and 2016. It was to address this lack of progress that, last year, we worked with Cancer Research UK and the University of Cambridge to set up a Children’s Brain Tumour Centre of Excellence, to discover and develop new treatments to tackle brain tumours in children.

We’re pleased that similar collaborative arrangements are now being established to address the equally difficult challenge of curing brain tumours in adults. ICR scientists have worked alongside other world-leading experts in the field, including, clinicians and researchers from six countries, to establish what challenges need to be addressed to ensure more people with brain tumours survive the disease.

The expert panel, convened by Cancer Research UK, has produced a Consensus Paper, highlighting the obstacles to progress, that we need to overcome in brain cancer research and treatment. This Paper has now been published in the journal Nature Reviews Clinical Oncology. Led by Professor Richard Gilbertson, the Director of the Cancer Research UK Children’s Brain Tumour Centre of Excellence at the University of Cambridge and the ICR, the new Position Paper sets out seven key challenges, that, must be, overcome in order to find new cures for brain cancers.

Many of these challenges are, already, the focus of research at the ICR and elsewhere, but the authors emphasise that there is much more work to be done, highlighting several areas for prioritisation. Research at the ICR is underpinned by generous contributions from our supporters. The first challenge is to redesign the research pipeline to make it more favourable to brain cancer research. In particular, the Consensus Statement criticises the disconnect between pre-clinical drug development and rigorous testing in the clinic.

Bridging this gap is something that the ICR has considerable expertise in. The ICR research strategy, developed jointly with the Royal Marsden NHS Foundation Trust, spells out how the agencies are applying the ‘bench-to-bedside’ approach to tackle cancer’s complexity and ability to adapt and evolve.

We are committed to opening up innovative new approaches to treatment, assessing these as quickly as we can in clinical trials and working to embed new treatment approaches in routine healthcare. We’re dedicated to applying this approach to all areas of our research, to ensure that our research has the greatest benefit to people living with cancer. And we believe our approach is very applicable to brain tumours. The second and third challenges laid out in the Position Paper encourage cancer researchers to use basic neuro-science research to its fullest and to improve our understanding of the microenvironment around brain tumours.

The authors explain that, while neuro-science research has given us a strong understanding of the cells, signalling pathways and blood vessels, that exist in the brain in the absence of cancer, this is not translating into a better understanding of the conditions specific to brain cancer. Instead, the two fields seem to be relatively separate and need to be joined up more effectively. More joint research into areas common to neuro-science and cancer, such as, immune dysfunction, seen in both cancer and dementia, would help to drive brain cancer research forward.

This synergy could help researchers to discover and develop new treatments, including, immune-therapies, an area, which the ICR and the Royal Marsden are prioritising. In fact, Professor Raj Chopra, the Head of our Division of Cancer Therapeutics and one of the Authors on the Paper, is leading the ICR’s efforts to discover a new wave of immune-therapies. The fourth challenge laid down in the Consensus Statement is for researchers to create new pre-clinical models of brain tumours. This is, particularly, important, given the rarity of many brain cancers and, therefore, the small number of patients, who can take part in clinical trials.

The ICR is, already, leading the way in the development of new approaches to model cancers in the lab. Last year, research led by Dr Nicola Valeri showed that ‘mini-tumours’, replica tumours grown in the lab from biopsy samples, could help to personalise treatments in a variety of digestive system cancers. And Dr Rachael Natrajan has been using similar techniques to test how a breast tumour’s genetics affect its growth. The next step will be to take this expertise and translate it into brain tumour research.

Challenge five is to improve our drugging of complex cancers. The authors encourage researchers to develop a better understanding of the biology of potential drug targets and to use advanced drug discovery approaches to find treatments, that hit these targets, a strong area of focus for ICR. A better understanding of the biology would, also, allow scientists to see how the disease adapts, evolves and progresses in response to treatment.

The ICR is, again, well positioned for this, as we discover more new cancer drugs than any other academic centre in the world. But, if, we are to rise to this challenge, we can’t and won’t rest on our laurels. We are committed to identifying new drug targets and to discovering innovative approaches to treatment, from adaptive, personalised targeted drug therapy to immune-therapy and precision radio-therapy.  And researchers in our Centre for Evolution and Cancer are finding ways to better understand cancer from an evolutionary perspective, including, using a tumour’s genetic history to predict how it will change in future and, therefore, to anticipate which approaches to treatment are likely to be most effective.

Putting precision medicine into action is the sixth challenge, laid out by the authors. They recommend that we move away from a categorisation of brain tumours, based, purely, on microscopic analysis and, instead, incorporate genomic profiling into brain tumour classification. Many of our researchers are, already, ahead of the game in this respect. Professor Richard Houlston, the Head of our Division of Genetics and Epidemiology, has led major studies into the genetic causes of glioma, gaining unprecedented insights.

Professor Houlston’s team has discovered, for example, that different sets of genes influence a person’s risk of developing the two subtypes of glioma, glioblastoma and non-glioblastoma, showing that what we thought were closely related diseases are, actually, very different. And recent research by Professor Chris Jones and colleagues has shown that, based on their genetic profiles, childhood brain tumours can be divided into 10 different diseases, suggesting that each one should be diagnosed and treated, based on its specific genetic faults. The next step will be to integrate these approaches into clinical trials that allow for the development of precision medicine.

The final challenge is to reduce the intensity and burden of treatment for some patients, in effect, balancing the likelihood of curing the disease with the side-effects of treatment. While the previously discussed challenges are important for long term success, the authors suggest that this one could yield the greatest patient benefit in the immediate future, by reducing the risk of treatment-related side-effects, particularly, in children.

Indeed, the ICR is, already, pioneering such a process in radiotherapy for breast and prostate cancers, with our research showing that a shorter course of treatment, with fewer, stronger doses, is as good as a longer course for treating the disease. In the medium to long term, our ability to make real progress in the treatment of brain tumours will depend very much on making substantial progress in the other six challenges, including, the integration of new and better data into diagnosis and treatment.

But the authors believe that this will be possible. The Consensus Paper gives the example of progress made with medullablastomas, where a breakthrough in understanding their biology led to a series of studies testing reduced doses of radio-therapy. While recognising that the seven challenges are ambitious, the authors of the expert report are optimistic for progress in the future. They believe, it is possible to achieve the changes needed to revolutionise brain tumour therapy but, also, caution that it will require much greater co-ordination and investment, as well as, a critical look at whether the approaches, that underpin brain cancer research today, are still capable of delivering designed outcomes.

The ICR will continue to lead the charge in taking innovative approaches to discovering and developing smarter, kinder treatments and we hope that the publication of this Paper will spur on others to join us and the brain tumour research community to achieve long term survival and eventual cures for adults and children with brain cancers.

::: Conor McKeever is Science Communications Officer at the Institute of Cancer Research London :::ω.

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Long-Term Benefits From Intensive Therapy in Early Stages of MS



|| February 22: 2019: Cardiff University News || ά. New findings by researchers at Cardiff University suggest that intensive therapy during the early stages of multiple sclerosis:MS leads to better long-term outcomes for patients, despite it, often, being viewed as a riskier option than other first line treatments. The research team looked at data from a cohort of 592 people with MS, treated in south Wales during the last 20 years.

The analysis, primarily, focused on the change in Expanded Disability Status Scale:EDSS, a method of quantifying disability in MS and monitoring changes in the level of disability at five years after starting treatment. Of the 592 people in the study, 104 were prescribed early intensive therapies whilst 488, initially, embarked on less risky, moderate-efficacy treatments.

Dr Emma Tallantyre, from Cardiff University’s Division of Psychological Medicine and Clinical Neurosciences, said, “Over the last 10-20 years we have seen huge advances in the treatment of relapsing-remitting MS, with over 12 licensed medications having been shown to suppress disease activity. However, the medications differ considerably in their efficacy and safety; the drugs with the strongest effect are, often, associated with the most worrisome risks.

As a result, there remains considerable uncertainty amongst clinicians and people with MS in how aggressively to treat the condition in its early stages, with high-efficacy early intensive therapies, often, reserved for those with rapidly evolving severe MS. Our study sought to explore long-term outcomes for people with MS according to their initial treatment strategy, either early intensive therapy, which is associated with a more complex safety profile or milder medications, which can be escalated to stronger drugs in the event of continued disease activity.

We found that in this cohort, long-term outcomes were more favourable following early intensive therapy versus first-line disease modifying therapies, suggesting that existing thresholds for this therapeutic approach, may be, too high and the delay imposed by escalation strategies, may, result in lost therapeutic opportunity.”

Professor Neil Robertson, of Neurology and a Co-author of the Study, said, “This data shows that in a very complex therapeutic landscape, routine data collected in NHS clinics has huge value in providing real-world evidence, that can help to answer the questions, that are important to patients.

Indeed, our findings have contributed to a successful award of over $10 million to fund DELIVER-MS, a multi-centre prospective trial of disease modifying therapy algorithms with participants in the UK and USA. In the meantime, there is work to be done in developing adequate procedures for treating patients using the escalation approach. These need to detect where first-line treatments are failing to slow the progression of the disease and respond by moving patients to more effective therapies without people developing permanent disability.”

Dr Susan Kohlhaas, the Director of Research at the MS Society, said, “People with MS, regularly, tell us that treatment decisions are difficult to make. This Study could be a game changer because it suggests people, who have early intensive treatment, have a better long term prognosis. We’re driving research into more and better therapies and are proud to have funded this work. The next step is to complete the DELIVER-MS trial, a phase two Study to compare the risks and benefits of this approach to one, where treatments escalate in intensity. Once complete, we hope, this could have really positive implications for people with MS.”

The Paper: Disease modifying therapy in MS: clinical outcomes of escalation versus early intensive treatment strategies: Published in JAMA Neurology:::ω.

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So How Does The Habenula Do It: Maintaining the Brain Pathways to Control Aversion: New Research Identifies the Mechanism




|| February 17: 2019: Karolinska Institutet News || ά. What happens in the brain when we feel discomfort? Researchers at Karolinska Institutet in Sweden are now one step closer to finding the answer. In a new Study, published in the journal Molecular Psychiatry, they identify, which pathways in the mouse brain control behaviour associated with aversion. Scientists have long been interested in how the brain creates signals, associated with negative emotions in order to better understand how imbalances in the same system can lead to affective disorders, such as, depression and anxiety.

The amygdala has long been the most commonly studied brain structure for understanding fear, whereas for rewards and positive signals the focus has been on the neuro-transmitter dopamine. But when it comes to areas of the brain, that control feelings of discomfort and aversion, much less is known. In the past few years, research has indicated that a brain structure, called, the habenula, controls positive and negative emotions in animal models. Moreover, clinical cases have been conducted with patients, suffering from depression, where deep brain stimulation of the habenula has been beneficial.

The habenula controls both dopamine and the neuro-transmitter serotonin, which is thought to play a significant part in the sense of wellbeing. However, it has not been known how the habenula is regulated. Researchers at Karolinska Institutet have now mapped which networks in the mouse brain control the habenula and what role they play in aversion.

“We’ve discovered a specific pathway, that goes between the hypothalamus and the habenula and that can be modulated, using opto-genetics to control the feeling of aversion.” says the Study Leader Docent Dinos Meletis at the Department of Neuroscience. “Our hope is that this can lead to the development of new treatments, that can rebalance the brain’s networks in, for example, depression or anxiety disorders.”

Using opto-genetics and other advanced methods, the group was able to identify the identity of the nerve cells and map their interconnections. Opto-genetics is a method, that uses light to activate specific neurons in order to study how the activation of different networks affects behaviour.

“This methodological revolution in brain research has made it possible to, functionally, study how different types of nerve cell and pathways, actually, control different types of behaviour, something, that was impossible to do only a decade ago.” says Dr Meletis.

The Study was supported by grants from the Swedish Research Council, the Swedish Foundation for Strategic Research, the Swedish Brain Foundation and Karolinska Institutet.

The Paper: A hypothalamus-habenula circuit controls aversion: Iakovos Lazaridis, Ourania Tzortzi, Moritz Weglage, Antje Märtin, Yang Xuan, Marc Parent, Yvonne Johansson, Janos Fuzik, Daniel Fürth, Lief E Fenno, Charu Ramakrishnan, Gilad Silberberg, Karl Deisseroth, Marie Carlén, Konstantinos Meletis: Molecular Psychiatry: Online: February 12: 2019

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New Research Finds Therapeutic Mechanism Identified in Patients With Schizophrenia


|| February 06: 2019: Karolinska Institutet News || ά. For unclear reasons, Schizophrenia patients have fewer connections between the neurons in the brain. Researchers at Karolinska Institutet, Sweden and Massachusetts General Hospital, USA, have now succeeded in creating human cell models, that show that there is an excessive degradation of connections in the brain of these patients and they have been able to link this to a genetic risk variant for the disease. They have, also, been able to show that the antibiotic minocycline inhibits the degradation and that treatment in adolescence can be linked to a reduced risk of developing Schizophrenia. The study is being published in the Journal Nature Neuro-science.

In the late adolescence, a normal extensive pruning of the number of connections between nerve cells, so-called, synapses, takes place through microglia, the brain’s immune cells, selectively, degrading less desirable connections. The process, referred to as, synaptic pruning, is of great importance for the development of functional neural networks. Many individuals succumb to Schizophrenia in their late adolescence, a period of intensive pruning in the brain. The researchers behind the study have created induced pluripotent stem cells:iPS from Schizophrenia patients and have reprogrammed them into neurons or brain cells.

Using a proprietary method, they have, then, created a model of the microglia synaptic pruning in a test tube. Comparisons with matched control subjects indicated a clear increase in the pruning of synapses in Schizophrenia patients. “We, also, conducted experiments where we combined nerve cells from healthy individuals and diseased microglia and vice versa and could conclude that the excessive pruning in the disease models was due to both a disrupted function of microglia and aberrations in the synapses.” says Ms Jessica Gracias, doctoral student at the Department of Physiology and Pharmacology, Karolinska Institutet, who is the Co-author of the study. 

The researchers, further, studied how different gene variants of the complement factor 4:C4 gene, affect the pruning. One variant of the complement factor proved to bind more strongly to synapses and result in the increased degradation of them. This is consistent with previous genetic findings, indicating that this specific C4 risk variant increases the risk of Schizophrenia.

“The use of human cells from patients made it possible to study the risk variants directly because mice lack these specified variants of the C4 gene.” says Dr Carl Sellgren Majkowitz, Research Group Leader at the Department of Physiology and Pharmacology, Karolinska Institutet, who is a Senior Consultant at Region Stockholm, who led the research project together with Roy Perlis at Massachusetts General Hospital.

Finally, microglia in the cell models were, also, ‘treated’ with an antibiotic, minocycline, which proved to inhibit the synaptic pruning. Using electronic data records from more than 20,000 individuals, who had received either minocycline or another antibiotic during adolescence, for treatment of acne, they were able to demonstrate a clear protective effect from minocycline treatment in relation to Schizophrenia onset.

The researchers hope that the findings will lead to more effective treatments for Schizophrenia, which can, then, also, be initiated early on in the event of an elevated genetic risk, for example.

The research was conducted at Massachusetts General Hospital and Karolinska Institutet and the National Institute of Mental Health, the Marianne and Marcus Wallenberg Foundation and the Swedish Research Council funded contributions to the research.

The Paper: The Paper: Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning: Carl M. Sellgren, Jessica Gracias, Bradley Watmuff, Jonathan D Biag, Jessica M Thanos, Paul B. Whittredge, Ting Fu, Kathleen Worringer, Hannah E Brown, Jennifer Wang, Ajamete Kaykas, Rakesh Karmacharya, Carleton P Goold, Steven D Sheridan and Roy H. Perlis: Published in Nature Neuroscience: Online: February 04: 2019

Caption: Researchers Jessica Gracias and Carl Sellgren Majkowitz: Image: Ada Trepci:::ω.

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