Culture

NUI Galway study compares the health of Irish children to those across Europe and Canada

A new report, Spotlight on Adolescent Health and Well-being, published today by WHO Regional Office for Europe, compiles extensive data on the physical health, social relationships and mental well-being of 227 441 schoolchildren aged 11, 13 and 15, from 45 countries. Irish children rank low on substance use such as smoking and drinking alcohol and high on physical activity. Ireland also ranks high for problematic social media use.
The report presents the comparative international findings of the Health Behaviour in School-aged Children (HBSC) survey, which is co-ordinated by the WHO and undertaken every four years. The Irish arm of this study is led by Professor Saoirse Nic Gabhainn in the Health Promotion Research Centre in NUI Galway.
In this new report Irish 11, 13 and 15 year olds are compared to those in 44 other countries across Europe and North America. Key comparative findings show that:

Irish children rank highly for eating breakfast and low for sugar-sweetened soft drink consumption at all ages. There have been significant reductions in sweets and soft drink consumption since 2014

Ireland ranks low at all ages for reported tobacco and alcohol use

Ireland ranks high relative to other countries in reported vigorous physical activity

Life satisfaction has significantly reduced since 2014, and Ireland ranks low for life satisfaction among 15-year olds

Ireland ranks highly for problematic social media use at all ages, and among 13 and 15 year olds, Ireland ranks highly for reports of having been cyberbullied.

The Irish Study

The Irish survey was carried out by the Health Promotion Research Centre at NUI Galway and was the sixth round of data collection in Ireland. The overall study aims to gain new insights, and increase our understanding of young people's health and wellbeing, health behaviours and their social context, both nationally and internationally.

As well as serving as a monitoring and a knowledge-generating function, one of the key objectives of HBSC has been to inform policy and practice, with the Irish section of the study being funded by the Department of Health. The cross-national survey covers diverse aspects of adolescent health and social behaviour, including self-assessment of mental health; body image; dietary habits; physical activity; school context; relationships with families and peers; tobacco, alcohol and cannabis use; bullying and injuries; and sexual health (for those aged 15 and above only). A special focus on online communication was included in the most recent HBSC survey, to better understand the expanding role of digital technology in young people's lives.

Kate O'Flaherty, Head of Health and Wellbeing at the Department of Health said: "This latest international study enables us to compare our progress in the area of child health and wellbeing with that of 45 other countries; our European neighbours and Canada. This study provides valuable international behavioural information recorded shortly before the onset of the Covid-19 pandemic; the next study will allow us to gauge the effect of the pandemic on teenage behaviour, health and wellbeing.

There are many areas where Ireland is doing well, for example our low smoking rates, low consumption of alcohol and sugar-sweetened drinks and comparatively good levels of physical activity. The areas of mental wellbeing and life satisfaction were comparatively less positive, and while there is already a lot of good work underway between Government Departments, agencies and other partners to address this, it will be of increased priority as we support wellbeing and resilience in the response to the Covid-19 pandemic."

Professor Saoirse Nic Gabhainn from the Health Promotion Research Centre at NUI Galway, and the Principal Investigator of the Irish HBSC study, commented on the Irish findings within the report: "This study provides valuable insight into the health and wellbeing of children in Ireland, and how we compare with children in other countries. It is positive to note we retain comparatively low rates of substance use and high rates of physical activity. The improvements in dietary behaviour in relation to lower intake of sweets and soft drinks are very welcome. However, there are also some areas that require further effort. For example, compared to other countries, Irish children report higher levels of problematic social media use than most countries and rates of cyberbullying are of concern. It is clear that more work is required to address the reductions in life satisfaction across all age groups."

Key Irish findings:

Health promoting behaviours

Daily breakfast consumption: Irish children ranked within the top 5 countries for the proportion of children reporting daily breakfast consumption

Meeting physical activity recommendations of at least one hour of moderate to vigorous physical activity (MVPA) daily: When compared to other countries, Ireland ranks in the top 10 for the proportion of 11 and 13 year-old boys and girls meeting physical activity recommendations. At all ages, a larger proportion of boys report meeting the recommendations than girls.

Risk-taking behaviour

Initiation of risk behaviours: In Ireland, the proportion of 11 and 13 year-old children reporting initiation of cigarette smoking and alcohol use is low relative to other countries

Drinking behaviours and tobacco use are continuing to improve in Ireland and when compared to other countries

Risky sexual behaviour: Girls in Ireland rank among the top 10 countries for not using the contraceptive pill or condom at last intercourse.

Mental Health and Well-being

Life satisfaction: Irish 15-year olds ranked within the bottom 2 countries for life satisfaction

Life satisfaction has significantly reduced in all age groups of Irish children since 2014

Ireland ranks low on reports of symptoms (stomachache, backache, nervous and dizziness at age 11

Girls at age 13 and 15 are more likely than boys to report multiple symptoms

High family affluence is related to better self-rated health, higher life satisfaction and lower rate of multiple symptoms.

Social interaction with family and peers

Perceived family support: Ireland ranked within the bottom ten countries for the proportion of 11 and 13 year-old children reporting high family support

Perceived family and peer support: have improved among 13 year-old girls since 2014.

Problematic social media use: Across all ages, Ireland ranked within the top 10 countries for the proportion of children categorised with problematic social media use

Bullied others at school: Ireland (13 and 15 year-olds) ranked within the bottom 10 countries for the proportion of children who report bullying others at school

Cyberbullying: Compared to other countries, Ireland ranks among the top 10 countries for prevalence of cyberbullying among older children (13 and 15 year-olds).

Data collected for the study are based on surveys completed by thousands of adolescents, thereby ensuring that their voices and concerns can be taken fully into account when the WHO frames its European strategies, policies and actions for improving child and adolescent health and well-being. The study feeds into a growing body of evidence calling for more effective and targeted interventions by governments and policy makers to tackle the effects of social, health and gender inequalities among young people in Europe.

Credit: 
University of Galway

Tick-borne encephalitis spread across Eurasia with settlers and their pets and prey

Researchers from Sechenov University together with colleagues from several Russian institutes analysed data on the RNA structure of tick-borne encephalitis virus. Much larger than in previous studies, the data volume of the new study allowed them to estimate the age of the virus subtypes and track its spread in Eurasia. The results of the study were published in the journal Viruses.

Tick-borne encephalitis is common in Central and Eastern Europe and a wide band in southern Siberia and the Far East. This disease is dangerous due to the ability of the virus to penetrate the brain and spinal cord, causing motor disorders, cognitive impairments and, in severe cases, paralysis and death. Every year in Russia, 1,500-2,000 people are infected, with about 30% developing neurological complications and 20-100 people dying.

The pathogen belongs to the genus Flavivirus (it also includes Zika virus and the virus that causes dengue fever) and is transmitted mainly through tick bites. There are three subtypes of the virus: Far Eastern, Siberian and European. Each of them is predominant in the region after which it is named, although this division is quite coarse - for example, cases of infection with the Siberian subtype were observed in the Baltic States and Sakhalin, and with the European one - in South Korea and the Altai Mountains. In recent years, the spread of the virus has expanded to northern areas (Kola Peninsula, Arkhangelsk Region) and mountainous regions (in Central Europe and Italy). In 2019, the first cases of infection were recorded in the UK and the Netherlands. To respond promptly to the emergence of the virus in new territories, it is necessary to understand what affects its spread and evolution. Existing studies provide different, sometimes contradictory results, but new data collected in recent years can clarify the situation.

The authors of the article used GenBank - a database that stores more than 200 million nucleotide sequences of RNA and DNA of various species. The data are supplied by scientists from different countries, and their volume is constantly growing, in common with the number of sequences describing the RNA of the tick-borne encephalitis virus - in ten years the number has increased fivefold.

Using computer algorithms, researchers compared the RNA of viruses found in different years on the territory of several countries. Knowing the 'distance' (the proportion of divergent nucleotides) between samples and the date of their receipt, one can estimate the time of divergence of species or the division of a species into subtypes. This method is based on the assumption that the sequence of nucleotides in a single species changes at an approximately constant rate, and is called the molecular clock. Using this method, scientists estimated the age of the most recent common ancestor for each of the subtypes. The result (about 700 and 900 years for the Siberian and Far Eastern subtypes, respectively) is consistent with earlier studies, while the age of the European subtype (about 1,600 years) was estimated for the first time after the virus was spotted in the Netherlands.

The researchers also tried to find out how genetically similar viruses of the same subtype ended up in different countries at a distance of thousands of kilometres from each other. There are several possible explanations. First, viruses (or ticks infected with them) can travel long distances with animals, such as migratory birds or bats. Second, human activity can contribute to the spread of the virus: transportation of livestock or introduction of animals suitable for hunting in new territories.

'The most important result of the work was that most of the virus spreading events occurred in the last three or four centuries, and in many cases we have observed the transfer of the virus for thousands of kilometres in the last 50-100 years, and viruses in Europe have completely mixed over the last 100-200 years,' said Alexander Lukashev, one of the authors of the work, Director of the Institute of Medical Parasitology and Tropical Medicine at Sechenov University. 'This allows us to consider tick-borne encephalitis as a highly dynamic disease, even as an emerging disease in many regions, and to think about an anthropogenic factor (the spread of infected ticks as a result of transportation of domestic and wild animals) as one of the main mechanisms behind the expansion of the virus.'

In addition, scientists have proposed an algorithm that simulates the compilation of samples as used in earlier studies. With its help, the authors of the article showed that the differences in results of previously published studies are well explained by the selection of the sequences included in the study.

Credit: 
Sechenov University

Study identifies the mechanism by which eating fish reduces risk of cardiovascular disease

image: Núria Amigó and Xavier Correig, researchers of the Universitat Rovira i Virgili, carried out the study together with researchers from Harvard Medical School, headed by Samia Mora.

Image: 
URV

A study by researchers from the Universitat Rovira i Virgili (URV) and Harvard Medical School has found that consuming omega 3 primarily through fish, but also in supplements containing these fatty acids, can modulate lipoproteins, that is, the particles that transport lipids through the blood, and can reduce the risk of cardiovascular disease. The association between the consumption of omega 3 and the reduction in the risk of suffering cardiovascular events has been demonstrated through the analysis of lipoprotein samples from 26,034 women, the largest and most detailed study ever carried out. The study is particularly important because cardiovascular disease is the most prevalent cause of death, with 1 in 3 people dying from cardiovascular events.

The research has been led by Núria Amigó, CEO of the URV spin off Biosfer Teslab and member of the Metabolomics Interdisciplinary Laboratory (MIL@b) - Metabolomics Platform, which was jointly created by the URV and the CIBERDEM and which is part of the Pere Virgili Health research Institute. Xavier Correig, professor from the Department of Electronic, Electrical and Automatic Engineering and director of the MIL@b - Metabolomics Platform, has participated in the study together with researchers from the Center for Lipid Metabolomics, Division of Preventive Medicine at the Brigham and Women's Hospital (Harvard Medical School) headed by Samia Mora.

Up to now it had been shown that a high consumption of omega 3 fatty acids was associated with lower levels of triglycerides in the blood. However, it had also been related to an increase in LDL cholesterol, that is, low-density cholesterol transported by lipoproteins, also known as bad cholesterol. LDL cholesterol increases the risk of cardiovascular diseases because it can accelerate the formation of atherosclerosis, that is, the process by which the arteries harden and lose their elasticity.

However, the study has found that increased consumption of LDL cholesterol from fish is associated principally with the cholesterol transported by the largest LDL particles, which are less atherogenic, and not with an increase in the total number of LDL particles. This decrease in the number of triglycerides transported by any type of lipoprotein helps protect the individual from heart disease.

The 3 types of omega 3 fatty acids studied, namely α-linoleic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are present in fish and other foods and are essential to human physiology, and the study has found that they differ in their association with the risk of cardiovascular disease. It found that there was no increase in the smallest LDL lipoproteins that transport cholesterol; instead the increase was among the largest LDL lipoproteins, which are not associated with the risk of heart disease. There was a decrease in all of the triglyceride-transporting particles and, moreover, the average size of the HDL and LDL particles increased, a phenomenon that is associated with increased protection from cardiovascular illness.

These conclusions have been obtained through mathematical modelling of the consumption of fish and omega 3 (both as a whole and of the different types ALA, DHA and EPA) and the profile of lipoproteins. The results were obtained by Nuclear Magnetic Resonance, "which can go further than simply analysing triglyceride and cholesterol content and can quantify the number and size of the different subtypes of plasmatic lipoprotein", explained Núria Amigó. She described how among the LDL particles that transport cholesterol "it is the smallest that are associated with a future cardiovascular event".

Another important element of the study is that the mathematical models used to evaluate the association between the consumption of fish and the reduction in cardiovascular risk have isolated other nutritional factors that affect the result, such as the consumption of other foods, the concentration of omega 3 according to the origin of the fish (wild or farmed) and traditional risk factors such as a sedentary lifestyle, age, body mass index and smoking.

The study analysed a cohort from the Women's Health Study by the Brigham and Women's Hospital, affiliated to Harvard Medical School, and involved the use of Nuclear Magnetic Resonance to characterise the plasma of 26,034 women with an average age of 53 (most were between 48 and 59).

Having confirmed that the risk factor associated with lipids, cholesterol concentration, triglycerides and the different subtypes of particles is modulated by the consumption of omega 3 fatty acids, "we now need to find out if the consumption of fish is associated with lower mortality from both cardiovascular diseases and other causes", Amigó explained, because "although the risk is lower in terms of lipids, we need to look at other pro-inflammatory factors and questions such as exposure to heavy metals".

Credit: 
Universitat Rovira i Virgili

Stroke rates among COVID-19 patients are low, but cases are more severe

DALLAS, May 21, 2020 -- The rate of strokes in COVID-19 patients appears relatively low, but a higher proportion of those strokes are presenting in younger people and are often more severe compared to strokes in people who do not have the novel coronavirus, while globally rates for stroke hospitalizations and treatments are significantly lower than for the first part of 2019, according to four separate research papers published this week in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

In "SARS2-CoV-2 and Stroke in a New York Healthcare System," researchers reported key demographic and clinical characteristics of patients who developed ischemic stroke associated with the COVID-19 infection and received care within one hospital system serving all 5 boroughs of New York City.

During the study period of March 15 through April 19, 2020, out of 3,556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging-proven ischemic stroke. They compared those 32 patients admitted with stroke and COVID-19 to those admitted only with stroke (46 patients) and found that the patients with COVID-19:

tended to be younger, average age of 63 years vs. 70 years for non-COVID stroke patients;

had more severe strokes, average score of 19 vs. 8 on the National Institutes of Health Stroke Scale;

had higher D-dimer levels, 10,000 vs. 525, which can indicate significant blood clotting;

were more likely to be treated with blood thinners, 75% vs. 23.9%;

were more likely to have a cryptogenic stroke in which the cause is unknown, 65.6% vs. 30.4%; and

were more likely to be dead at hospital discharge, 63.6% vs. 9.3%.

Conversely, COVID-19 stroke patients were less likely than those stroke patients without the novel coronavirus to have high blood pressure (56.3% vs. 76.1%) or to have a prior history of stroke (3.1% vs. 13%).

The researchers observed that the rate of imaging-confirmed acute ischemic stroke in hospitalized patients with COVID-19 in their New York City hospital system was lower compared to prior reports in COVID-19 studies from China. One reason for the difference might be related to variations in race/ethnicity between the two study populations. In addition, the low rate of ischemic stroke with COVID-19 infection may be an underestimate because "the diagnosis of ischemic stroke can be challenging in those critically ill with COVID-19 infection who are intubated and sedated," said lead study author Shadi Yaghi, M.D., FAHA, of the department of neurology at NYU Grossman School of Medicine in Manhattan.

Yaghi said, "It was difficult to determine the exact cause of the strokes of the COVID-19 patients, however, most patients appeared to experience abnormal blood clotting. Additional research is needed to determine if therapeutic anticoagulation for stroke is useful in patients with COVID-19." The researchers noted that at least one clinical trial is already underway to investigate the safety and efficacy of treatment for active clotting vs. preventive treatment in certain patients with COVID-19 infection presenting with possible clotting indicators.

Yaghi and his coauthors also noted the number of stroke cases with COVID-19 seems to have peaked and is now decreasing. This finding may be related to the overall reduction in COVID-19 hospital admissions, which may be due to social distancing and guidance for people to stay at home. In addition, the number of stroke patients hospitalized during the study period was significantly lower than the same time frame in 2019.

Similar trends are reported in several other studies also published this week in Stroke, reflecting a global disruption of emergency health care services including delayed care and a lower-than-usual volume of stroke emergencies during the COVID-19 pandemic crisis.

In a Hong Kong study, "Delays in Stroke Onset to Hospital Arrival Time during COVID-19," by lead author Kay Cheong Teo, M.B.B.S., researchers compared the stroke onset time to hospital arrival time for stroke and transient ischemic attack (TIA) patients from Jan. 23 to March 24, 2020 (the first 60 days from the first diagnosed COVID-19 case in Hong Kong) to the same time period in 2019. In 2020, 73 stroke patients presented to Queen Mary Hospital compared to 83 in 2019. However, the time from stroke onset-to-arrival time was about an hour longer in 2020 compared with last year (154 minutes vs. 95 minutes). In addition, the number of patients arriving within the critical 4.5-hour treatment window dropped from 72% in 2019 to 55% in 2020.

Also from China, "The impact of the COVID-19 epidemic on stroke care and potential solutions," by lead author Jing Zhao, M.D., Ph.D., detailed survey results from more than 200 stroke centers through the Big Data Observatory Platform for Stroke of China, which consists of 280 hospitals across China. They found that in February 2020, hospital admissions related to stroke dropped nearly 40%, while clot-busting treatment and mechanical clot-removal cases also decreased by 25%, compared to the same time period in 2019. The researchers cited several factors likely contributed to the reduced admissions and prehospital delays during the COVID-19 pandemic, such as lack of stroke knowledge and proper transportation. They also noted that another key factor was patients not coming to the hospital for fear of virus infection.

In a fourth study, "Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak," by lead author Basile Kerleroux, M.D., researchers in France compared patient data from stroke centers across the country from February 15 through March 30, 2020 to data of patients treated during the same time period in 2019. They found a 21% decrease (844 in 2019 vs. 668 in 2020) in overall volume of ischemic patients receiving mechanical thrombectomy during the pandemic compared to the previous year.

Additionally, there was a significant increase in the amount of time from imaging to treatment overall -- 145 minutes in 2020 compared to 126 minutes in 2019, and that delay increased by nearly 30 minutes in patients transferred to other facilities for treatment after imaging. The researchers said delays may have been due to unprecedented stress on emergency medical system services, as well as primary care stroke centers lacking transfer resources needed to send eligible patients to thrombectomy capable stroke centers within the therapeutic window. They noted stricter applications of guidelines during the pandemic period could also have meant some patients may have not been referred or accepted for mechanical thrombectomy treatment during that time.

Credit: 
American Heart Association

MIPT biophysicists found a way to take a peek at how membrane receptors work

image: MIPT biophysicists explained ways to visualize membrane receptors in their different states. Detailed information on the structure and dynamics of these proteins will enable developing effective and safe drugs to treat many sorts of conditions.

Image: 
Daria Sokol/MIPT Press Office

In a study published in Current Opinion in Structural Biology, MIPT biophysicists explained ways to visualize membrane receptors in their different states. Detailed information on the structure and dynamics of these proteins will enable developing effective and safe drugs to treat many sorts of conditions.

Every second, living cells receive myriads of signals from their environment, which are usually transmitted through dedicated signaling molecules such as hormones. Most of these molecules are incapable of penetrating the cell membrane so for the most part, such signals are identified at the membrane. For that purpose, the cell membrane is equipped with cell-surface receptors.

That receive outside signals and "interpret" them into the language the cell can understand. Cell surface receptors are vital for proper functioning of cell and the organism as a whole. Should the receptors stop working as intended, the communication between cells becomes disrupted, which leads to the organism developing a medical condition.

GPCRs (G protein-coupled receptors) is a large family of membrane receptors that share a common structure; they all have seven protein spirals that cross the membrane and couple the receptor to a G protein situated on the inside of the cell. Interaction of the signal molecule with the receptor triggers a change in the 3D structure, or conformation, of the receptor, which activates the G protein. The activated G protein, in turn, triggers a signal cascade inside the cell, which results in a response to the signal.

GPCR family membrane proteins have been linked to a lot of neurodegenerative and cardiovascular diseases and certain types of cancer. GPCR proteins have also been proven to contribute to conditions such as obesity, diabetes, mental disorders, and others (fig. 2). As a result, GPCRs have become a popular drug target, with a large number of drugs currently on the market targeting this particular family of receptors.

One of the modern approaches to drug development involves analyzing 3D structures of GPCR molecules. But membrane receptor analysis is a slow and extremely laborious process and even when successful, it does not completely reveal the molecule's behavior inside the cell.

"Currently, scientists have two options when it comes to studying proteins. They can either 'freeze' a protein and have its precise static snapshot, or study its dynamics at the cost of losing details. The former approach uses methods such as crystallography and cryogenic electron microscopy; the latter uses spectroscopic techniques," comments Anastasia Gusach, a research fellow at the MIPT Laboratory of Structural Biology of G-protein Coupled Receptors.

The authors of the study demonstrated how combining both the structural and the spectroscopic approaches result in "the best of both worlds" in terms of obtaining precise information on functioning of GPCRs (fig. 3). For instance, the double electron-electron resonance (DEER) and the Förster resonance energy transfer (FRET) techniques act as an "atomic ruler", ensuring precise measurements of distances between separate atoms and their groups within the protein. The nuclear magnetic resonance method enables visualizing the overall shape of the receptor molecule while modified mass spectrometry methods (MRF-MS, HDX-MS) help trace the susceptibility of separate groups of atoms constituting the protein to the solvent, thus indicating which parts of the molecule face outwards.

"Studying the GPCR dynamics uses cutting-edge methods of experimental biophysical analysis such as nuclear magnetic resonance (NMR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, and advanced fluorescence microscopy techniques including single-molecule microscopy," says Alexey Mishin, deputy head of the MIPT Laboratory for Structural Biology of G-protein Coupled Receptors.

"Biophysicists that use different methods to study GPCRs have been widely organizing collaborations that already bore some fruitful results. We hope that this review will help scientists specializing in different methods to find some new common ground and work together to obtain a better understanding of receptors' functioning." adds Anastasia Gusach.

The precise information on how the membrane receptors function and transfer between states will greatly expand the capabilities for structure-based drug design.

Credit: 
Moscow Institute of Physics and Technology

Emerging evidence on genetics of schizophrenia raises hopes for new treatment targets

May 21, 2020 - In recent years, genome-wide association studies (GWAS) have identified many different genetic variants associated with schizophrenia. These genetic discoveries raise the promise of developing urgently needed new treatments targeting the underlying biology and pathophysiology of schizophrenia, according to a special article in the Journal of Clinical Psychopharmacology. The journal is published in the Lippincott portfolio by Wolters Kluwer.

In a translational science update, Rebecca Birnbaum, MD, of Icahn School of Medicine at Mount Sinai, New York, and Daniel R. Weinberger, MD, of Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, review efforts to bridge the gap between new genetic findings and innovative treatments for schizophrenia. "None of the medicines used in psychiatry were initially discovered based on an understanding of the causes or basic mechanisms of psychiatric illnesses," Dr. Weinberger comments.

Dr. Birnbaum adds: "The discovery of genetic risk factors for schizophrenia and other psychiatric diagnoses represent important clues to changing this history, to discovering treatments based on biological mechanisms of causation."

Genetic Associations May Lead to New Treatments for Schizophrenia

The first medications for schizophrenia were discovered serendipitously in the 1950s, with subsequent "me-too" drugs targeting the same limited number of neurotransmitters. While these antipsychotic drugs have benefits in addressing some of the symptoms of schizophrenia, they don't necessarily target all of the potential underlying causes.

With advances in GWAS, researchers are identifying increasing numbers of genetic variants - some relatively common, others rare - associated with schizophrenia. Although the effects of individual genetic variants on schizophrenia risk may be minor, further studies of the genes and pathways they affect might lead to new understanding of the neurobiology of schizophrenia.

Studies of gene expression may provide new insights into the mechanisms by which schizophrenia develops, as well as possible "druggable targets" for new medications. Genes or pathways implicated by both common and rare variants might be especially strong candidates for new drugs. Systems biology approaches - targeting brain functional networks or biological modules affected by schizophrenia risk genes - might be more promising than trying to develop drugs targeting any individual gene.

Neurodevelopmental studies indicate that processes leading to schizophrenia begin very early, suggesting that treatments may be most effective in early life or even the fetal period. Newly discovered genetic associations might also have implications for "precision psychiatry" - using genetic markers to assess individual differences in risk, or to select the most effective treatment for individual patients.

Despite the promise of advances in understanding the genetics of schizophrenia, difficult challenges lie ahead in translating these discoveries into real treatment advances for patients with schizophrenia and other psychiatric disorders. "Translating susceptibility genes into new therapeutic interventions will require extensive investigation and probably some luck," says Dr. Weinberger. "Nevertheless, we are on the threshold of a sea change opportunity in clinical pharmacology."

Credit: 
Wolters Kluwer Health

The European viper uses cloak-and-dazzle to escape predators

image: The viper's zig-zag pattern helps the snake remain undetected, it also provides a warning of the snake's dangerous defense and it can produce an illusionary effect that may hide the snake's movement as it flees.

Image: 
The University of Jyväskylä/Janne Valkonen

Research of the University of Jyväskylä demonstrate that the characteristic zig-zag pattern on a viper's back performs seemingly opposing functions during a predation event. At first, the zig-zag pattern helps the snake remain undetected. But upon exposure, it provides a conspicuous warning of the snake's dangerous defense. Most importantly the zig-zag can also produce an illusionary effect that may hide the snake's movement as it flees. The research, published in Animal Behaviour 164 (2020), reveals how a single color pattern can have multiple effects during a predation event, thereby expanding the discussion on protective coloration and anti-predator adaptations.

Protective coloration is one of the simplest but most effective tools that prey species use to evade predators. Typically, different color patterns are useful at different stages of a predation event. Some color patterns are cryptic, obscuring the prey from being detected - think chameleons. Other patterns are aposematic, which blatantly advertise a warning to predators - think wasps. Finally, some patterns can produce optical illusions to startle or confuse predators and give the prey an escape opportunity - think zebras.

But a recent series of experiments, by a team headed by Janne Valkonen and Johanna Mappes at the University of Jyväskylä (Finland), suggests that European vipers (Vipera sp.) can achieve all three tricks with a single color pattern - their characteristic zig-zag.

At first, the zig-zag pattern helps the viper to hide. The researchers hid plasticine models of snakes with different color patterns along paths and noted how often they were detected by people walking the trail. Models with the zig-zag pattern were detected less often than plainly colored models. This is the first confirmation that the viper's zig-zag pattern provides a cryptic function. But even if the viper is detected, the zig-zag can still work its magic - instead of hiding the snake, the pattern now functions to make it more obvious. Previous research has already established that the pattern warns predators about the snake's dangerous bite.

The rapid flickering from the zigs and zags of a fleeing snake can produce a a 'flicker-fusion effect' to mammalian predators

The most significant contribution from Dr. Janne Valkonen's study deals with a particular class of illusion generated by the zig-zag pattern. Just as how a rapid series of still pictures can produce a smooth animation, the rapid flickering from the zigs and zags of a fleeing snake can produce a solid shape.

Team measured the speed of fleeing snakes and calculated the flicker rate of the zig-zag. To an observer, a rapidly changing stimulus (such as a moving zig-zag, or spinning helicopter blade) is perceived as continuous if the flicker rate exceeds a threshold in the visual system.

The researchers found that the zig-zag moved quickly enough to produce such a 'flicker-fusion effect' to mammalian predators, although the quicker eyes of a raptor won't be fooled. The effect of this illusion may change the appearance of the moving snake, making it harder to catch. So, like a skilled illusionist, the viper hides by revealing.

The viper's zig-zag seems to be a simple pattern, but it is a masterful illusion that can hide, reveal, and paradoxically achieve both at the same time. Similarly, this research resolves theoretical tensions between apparently opposing functions of color patterns. That is, crypsis and aposematism seem mutually exclusive: one is meant to blend an animal into its surroundings, the other to make it stand out.

However, through the magic of movement and optics, both functions can be gained through the same pattern at different stages in the predation sequence. Furthermore, the one-to-many aspect of the zig-zag to its antipredator functions implies a far broader scope for the evolution of color patterns and antipredator adaptations than simple one pattern-to-one function relations.

Credit: 
University of Jyväskylä - Jyväskylän yliopisto

Autistic burnout

image: Journal dedicated to research and scholarship on the most pressing issues affecting adults on the autism spectrum, from emerging adulthood to later life

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, May 21, 2020 "What is autistic burnout has been a term frequently used by autistic adults? Its characteristics, and what may cause or alleviate it, are discussed in Autism and Adulthood.

Autistic adults use the term to describe a chronic state of exhaustion, loss of skills, and reduced tolerance to stimulus. These characteristics are long-lasting and permeate peoples lives.

According to the study, autistic adults say chronic life stress and a mismatch of expectations and abilities without adequate supports is very difficult. Autistic burnout had a negative impact on autistic adults health, capacity to live independently, and quality of life, including suicidal behavior.

Autistic burnout has been a matter of extreme and under-examined urgency for far too long. I hope our work opens a new avenue of research into understanding, relieving, and preventing it in our community, says coauthor Dora Raymaker, PhD, Portland State University.

While the autistic community frequently talks about autistic burnout, the concept has been almost completely absent in the scientific and clinical literature. Its time we start listening to autistic adults and pay attention to what may be an important mediator of poor outcomes, says senior author, Christina Nicolaidis, MD, MPH, Portland State University and Oregon Health & Science University, Portland, Oregon, and Editor-in-Chief of Autism in Adulthood.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

Scientists identify chemicals in noxious weed that 'disarm' deadly bacteria

image: Emory University ethnobotanist Cassandra Quave, shown in her lab with berries from the Brazilian peppertree. The plant is native to South America where traditional healers in the Amazon have used it as a treatment for skin infections.

Image: 
Emory University

Scientists have identified specific compounds from the Brazilian peppertree -- a weedy, invasive shrub in Florida -- that reduce the virulence of antibiotic-resistant staph bacteria. Scientific Reports published the research, demonstrating that triterpenoid acids in the red berries of the plant "disarm" dangerous staph bacteria by blocking its ability to produce toxins.

The work was led by the lab of Cassandra Quave, an assistant professor in Emory University's Center for the Study of Human Health and the Emory School of Medicine's Department of Dermatology. The researchers' laboratory experiments provide the first evidence that triterpenoid acids pack a punch against methicillin-resistant Staphylococcus aureus, known as MRSA.

The Brazilian peppertree (Schinus terebinthifolia), native to South America, is also abundant in Florida, where it forms dense thickets that crowd out native species. "It is a noxious weed that many people in Florida hate, for good reason," Quave says. "But, at the same time, there is this rich lore about the Brazilian Peppertree in the Amazon, where traditional healers have used the plant for centuries to treat skin and soft tissue infections."

Quave, a leader in the field of medical ethnobotany and a member of the Emory Antibiotic Resistance Center, studies how indigenous people incorporate plants in healing practices to uncover promising candidates for new drugs.

The Centers for Disease Control and Prevention calls antibiotic resistance "one of the biggest public health challenges of our time." Each year in the U.S., at least 2.8 million people get antibiotic-resistant infections, leading to more than 35,000 deaths.

"Even in the midst of the current viral pandemic of COVID-19, we can't forget about the issue of antibiotic resistance," Quave says. She notes that many COVID-19 patients are receiving antibiotics to deal with secondary infections brought on by their weakened conditions, raising concerns about a later surge in antibiotic-resistant infections.

In 2017, the Quave lab published the finding that a refined, flavone-rich mix of 27 compounds extracted from the berries of the Brazilian peppertree inhibits formation of skin lesions in mice infected with MRSA. The extract works not by killing the MRSA bacteria, but by repressing a gene that allows the bacteria cells to communicate with one another. Blocking that communication prevents the cells from taking collective action, which essentially disarms the bacteria by preventing it from excreting the toxins it uses to damage tissues. The body's immune system then stands a better chance of healing a wound.

That approach is different from the typical treatment of blasting deadly bacteria with drugs designed to kill them, which can help fuel the problem of antibiotic resistance. Some of the stronger bacteria may survive these drug onslaughts and proliferate, passing on their genes to offspring and leading to the evolution of deadly "super bugs."

For the current paper, the researchers wanted to narrow down the scope of 27 major compounds from the berries to isolate the specific chemicals involved in disarming MRSA. They painstakingly refined the original compounds, testing each new iteration for its potency on the bacteria. They also used a series of analytical chemistry techniques, including mass spectrometry, nuclear magnetic resonance spectroscopy and X-ray crystallography to gain a clear picture of the chemicals involved in the anti-virulence mechanism.

The results showed that three triterpenoid acids worked equally well at inhibiting MRSA from forming toxins in a petri dish, without harming human skin cells. And one of the triterpenoid acids worked particularly well at inhibiting the ability of MRSA to form lesions on the skin of mice. The researchers also demonstrated that the triterpenoid acids repressed not just one gene that MRSA uses to excrete toxins, but two genes involved in that process.

"Nature is the best chemist, hands down," Quave says. She adds that weeds, in particular, tend to have interesting chemical arsenals that they may use to protect them from diseases so they can more easily spread in new environments.

The research team plans to do further studies to test the triterpenoid acids as treatments for MRSA infections in animal models. If those studies are promising, the next step would be to work with medicinal chemists to optimize the compounds for efficacy, delivery and safety before testing on humans.

"Plants are so incredibly complex chemically that identifying and isolating particular extracts is like picking needles out of haystacks," Quave says. "When you're able to pluck out molecules with medicinal properties from these complex natural mixtures, that's a big step forward to understanding how some traditional medicines may work, and for advancing science towards a potential drug development pathway."

Credit: 
Emory Health Sciences

COVID-19 evidence and strategies for orthopaedic surgeons

May 21, 2020 - How should orthopaedic surgeons respond to the COVID-19 pandemic? A review in The Journal of Bone & Joint Surgery analyzes evidence and strategies for managing the novel SARS-CoV-2 virus - including critical lessons from past pandemics. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Controlling the spread of COVID-19 has become the singular focus on several countries, with unprecedented international collaboration and rapid dissemination of emerging scientific evidence," according to the rapid evidence review by Mohit Bhandari, MD, PhD, FRCSC, and colleagues of McMaster University, Hamilton, Ont., Canada. In a comprehensive review, they identify and analyze available evidence on the COVID-19 pandemic.

COVID-19 - Emerging Evidence and Evolving Strategies

Although the global spread and societal impact of SARS-CoV-2 may seem unprecedented, it is the third major outbreak of coronavirus infection to occur in less than 20 years - following severe acute respiratory syndrome (SARS) in 2002-03 and Middle East Respiratory Syndrome (MERS) in 2012.

Symptoms of COVID-19 - most commonly fever and cough - appear an average of five days after infection and almost always within 11.5 days. Evidence suggests that about 20 percent of cases are severe or critical, while about 88 percent have abnormal findings on chest CT scans. Estimates of mortality vary but may approach four percent in confirmed cases of COVID-19. Older patients and those with comorbid conditions, such as cardiovascular disease and diabetes, are at higher risk of death.

There is currently no specific treatment for COVID-19. Trials are underway to evaluate antivirals and other potentially beneficial medications; some of these treatments "may be trialed if available in severe cases." The race is on to develop an effective vaccine against SARS-CoV-2, with several potential targets being evaluated. However, as the authors write, "[A] vaccine that is ready for widespread use is likely still months, possibly years, away."

In the meantime, hygiene, social distancing, and isolation measures are needed to curb virus transmission. Experience suggests that these measures have been effective in "flattening the curve" of viral transmission - as demonstrated by the textbook example of the 1918 influenza pandemic. In that historic epidemic as in the SARS pandemic, a second wave of infections occurred after relaxation of containment measures.

"It is essential that we continue these practices, as the outbreak is currently expected to last for many more months and we must be mindful of the lessons learned from past pandemics to prevent a second wave from occurring," according to Dr. Bhandari and colleagues. That's especially important in limiting the spread of SARS-Cov-2 by asymptomatic and pre-symptomatic individuals.

Guiding Surgeons Through the Pandemic

The authors summarize recent guidance to surgeons and other frontline healthcare professionals, including postponing or cancelling elective or nonemergency surgical procedures; shifting inpatient tests or procedures to outpatient settings, if possible; and taking steps to conserve available resources and healthcare capacity. The review includes recommended steps for necessary surgery in patients with COVID-19.

Dr. Bhandari is Editor-in-Chief of OrthoEvidence, a global online source for high quality and timely orthopedic-only, evidence-based summaries. In partnership with JBJS, OrthoEvidence has created a COVID-19 Resource Center, offering podcasts, original content, links to critical breaking studies, and global perspectives on COVID-19 from orthopaedic surgeons around the world on how they're responding to the pandemic.

"Data is the differentiator in this global crisis," Dr. Bhandari writes in a message to the OrthoEvidence community. "We are proud to stand with our community to provide as much evidence as we can to help you all make important decisions for your communities and your patients."

Click here to read "Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies."
DOI: 10.2106/JBJS.20.00396

Credit: 
Wolters Kluwer Health

Lungs of deceased COVID-19 patients show distinctive features

In a new study in the New England Journal of Medicine (NEJM), senior author, Steven J. Mentzer, MD, thoracic surgeon at Brigham and Women's Hospital, and a team of international researchers examined seven lungs obtained during autopsy from patients who died of COVID-19. They compared this group to seven autopsied lungs obtained from patients who died of acute respiratory distress syndrome secondary to influenza A (H1N1) infection as well as to 10 age-matched uninfected control lungs.

Both COVID-19 and influenza are the same category of virus and both infect the respiratory tract. While the lungs shared some common features, there were distinctive features related to blood vessels seen in the lungs of patients who had died of COVID-19.

Researchers observed that COVID-19 damaged the endothelial cells (vascular lining cells), causing severe endothelial injury. Patients with COVID-19 showed widespread blood clotting as well as new vessel growth -- the latter likely a result of the body's response to the virus. The team saw signs of a distinctive pattern of pulmonary vascular disease progression in some cases of COVID-19 compared to that of equally severe influenza virus infection.

Some of the key points are highlighted below:

COVID-19 is a respiratory virus that causes a vascular disease.

The damage to vascular cells helps explain the serious blot clotting observed in patients.

A unique response, intussusceptive angiogenesis (IA), is the way the body compensates for the thrombosis and blood vessel damage.

Damaged blood vessels may also underlie other problems seen, such as COVID toe, children with Kawasaki, stroke, and other seemingly unrelated problems seen with COVID-19.

This study shows the need for more research on angiogenesis and the vascular effects of COVID-19.

Credit: 
Brigham and Women's Hospital

Hearts that drum together beat together

Group work and cooperation are crucial in everyday life. As such, it is important to explore the avenues by which synchrony within a group may enhance cohesion and influence performance.

What role can music play in this effort? In an interdisciplinary study published today in the journal Scientific Reports researchers report their discovery that while drumming together, aspects of group members' heart function - specifically the time interval between individual beats (IBI) -- synchronized.

This physiological synchronization was recorded during a novel musical drumming task that was especially developed for the study in a collaboration between social-neuroscientists and scholars from the Music Department at Israel's Bar-Ilan University.

The drumming involved 51 three-participant groups in which IBI data were continuously collected. Participants were asked to match their drumming -- on individual drumming pads within an electronic drum set shared by the group -- to a tempo that was presented to the group through speakers. For half of the groups, the tempo was steady and predictable, and thus, the resulting drumming and its output were intended to be synchronous. For the other half, the tempo changed constantly and was practically impossible to follow, so that the resulting drumming and musical output would be asynchronous. The task enabled the researchers to manipulate the level of behavioral synchronization in drumming between group members and assess the dynamics of changes in IBI for each participant throughout the experiment.

Following this structured drumming task, participants were asked to improvise drumming freely together. The groups with high physiological synchrony in the structured task showed more coordination in drumming in the free improvisation session.

Analysis of the data demonstrated that the drumming task elicited an emergence of physiological synchronization in groups beyond what could be expected randomly. Further, behavioral synchronization and enhanced physiological synchronization while drumming each uniquely predicts a heightened experience of group cohesion. Finally, the researchers showed that higher physiological synchrony also predicts enhanced group performance later on in a different group task.

"Our results present a multi-modal behavioral and physiological account of how synchronization contributes to the formation of the group bond and its consequent ability to cooperate," says Dr. Ilanit Gordon, head of the Social Neuroscience Lab at Bar-Ilan University's Department of Psychology and a senior researcher at the University's Gonda (Goldschmied) Multidisciplinary Brain Research Center, who led the study together with Prof. Avi Gilboa and Dr. Shai Cohen, of the Department of Music. "A manipulation in behavioral synchrony and emerging physiological coordination in IBI between group members predicts an enhanced sense of cohesion among group members."

"We believe that joint music making constitutes a promising experimental platform for implementing ecological and fully interactive scenarios that capture the richness and complexity of human social interaction," says Prof. Gilboa, of the Department of Music, who co-authored the study. "These results are particularly significant due to the crucial importance of groups to action, identity and social change in our world."

Credit: 
Bar-Ilan University

Brain's 'updating mechanisms' may create false memories

Senior author Professor Bryce Vissel, from the UTS Centre for Neuroscience & Regenerative Medicine, said his team used novel behavioural, molecular and computational techniques to investigate memories that have not been well-formed, and how the brain deals with them.

He explained, "For memories to be useful, they have to have been well-formed during an event - that is, they have to accurately reflect what actually happened.

"However, in the real world many memories are likely to be inaccurate - especially in situations where the experience was brief, sudden or highly emotional, as can often occur during trauma. Inaccurate memories can also occur when the memory is poorly encoded, potentially as a result of subtle differences in how each person processes memory or because of disease like Alzheimer's or dementia."

Lead author Dr Raphael Zinn said, "Our findings are exciting because they show that memory updating mechanisms that become activated after recall can refine and improve memories.

"Surprisingly, we found that the same process can, in some circumstances, lead to incorrect updating of the memory. We also identify one molecular mechanism, called reconsolidation, which could be mediating this process.

"This suggests we might be able to target such updating mechanisms therapeutically to treat memory and anxiety disorders where memory formation is poor."

The 6-year study shows that the same mechanism that updates poor memories can also severely distort them if it occurs in the wrong situation.

Professor Vissel said these findings could be useful for understanding memory fallibility in everyday life; fear and memory disorders, post-traumatic stress disorder (PTSD); and situations where accurate recall is critical, like witness testimony in courtrooms.

"While these findings come from studies in mice, this research is likely to apply across many animals with developed brains, including other mammals and humans. They might also tie in with dementias, where the main memory-related problem is an apparent inability to form accurate new memories.

"Why is memory fallible? Our study suggests that when an individual forms a poor memory, the brain reactivates the memory in a similar situation and then updates it. Sometimes a poorly formed memory can be wrongly reactivated in a similar, but irrelevant, situation. The brain may then update the memory from that irrelevant situation, causing the memory to become incorrect - rather than creating a new and entirely different memory of the new situation."

Credit: 
University of Technology Sydney

Patients with COVID-19 may develop thyroid infection

WASHINGTON--COVID-19 infection may cause subacute thyroiditis, according to a new case study published in The Journal of Clinical Endocrinology & Metabolism.

Subacute thyroiditis is an inflammatory thyroid disease characterized by neck pain and is usually preceded by an upper respiratory tract infection. It may be caused by a viral infection or a post-viral inflammatory reaction, and many viruses have been linked to the disease.

SARS-CoV-2 (COVID-19) has emerged as a pandemic with severe respiratory symptoms and may involve other organs. More than 3 million cases of COVID-19 have been confirmed worldwide.

"We reported the first case of subacute thyroiditis after SARS-CoV-2 infection," said Francesco Latrofa, M.D., of the University Hospital of Pisa in Pisa, Italy. "Physicians should be alerted about the possibility of this additional clinical manifestation related to COVID-19."

The clinicians examined an 18-year-old woman who was infected with COVID-19 after being exposed by her father. She completely recovered from COVID-19, testing negative a few days later, but started experiencing some additional symptoms. The young woman had neck and thyroid pain, fever and an increased heart rate. She was sent back to the hospital, where she was diagnosed with subacute thyroiditis. She had normal thyroid functioning and imaging just one month earlier.

"Because of the chronological association, SARS-CoV-2 may be considered accountable for the onset of subacute thyroiditis," Latrofa said.

Credit: 
The Endocrine Society

Investigation of COVID-19 outbreak in independent/assisted living facility

What The Study Did: The implementation of surveillance for SARS-CoV-2 is examined in this case series that describes symptoms of COVID-19 among residents and staff of an independent/assisted living community.

Authors: Alison C. Roxby, M.D., M.Sc., of the University of Washington in Seattle, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.2233)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network