Carbon Chemist

Tag: Autism

  • Attacks on emergency room workers prompt debate over tougher penalties

    Attacks on emergency room workers prompt debate over tougher penalties

    [ad_1]

    Ravera, an ER nurse at Sutter Medical Center in Sacramento, recalled an incident in which an agitated patient wanted to leave. “Without any warning he just reached up, grabbed my glasses, and punched me in the face,” said Ravera, 54. “And then he was getting ready to attack another patient in the room.” Ravera and hospital security guards subdued the patient so he couldn’t hurt anyone else.

    Violence against health care workers is on the rise, including in the ER, where tensions can run high as staff juggle multiple urgent tasks. Covid-19 only made things worse: With routine care harder to come by, many patients ended up in the ER with serious diseases — and brimming with frustrations.

    In California, simple assault against workers inside an ER is considered the same as simple assault against almost anyone else, and carries a maximum punishment of a $1,000 fine and six months in jail. In contrast, simple assault against emergency medical workers in the field, such as an EMT responding to a 911 call, carries maximum penalties of a $2,000 fine and a year in jail. Simple assault does not involve the use of a deadly weapon or the intention to inflict serious bodily injury.

    State Assembly member Freddie Rodriguez, who worked as an EMT, has authored a bill to make the punishments consistent: a $2,000 fine and one year in jail for simple assault on any on-the-job emergency health care worker, whether in the field or an ER. The measure would also eliminate the discrepancy for simple battery.

    Patients and family members are assaulting staff and “doing things they shouldn’t be doing to the people that are there to take care of your loved ones,” said Rodriguez, a Democrat from Pomona. The bill passed the state Assembly unanimously in January and awaits consideration in the Senate.

    Rodriguez has introduced similar measures twice before. Then-Gov. Jerry Brown vetoed one in 2015, saying he doubted a longer jail sentence would deter violence. “We need to find more creative ways to protect the safety of these critical workers,” he wrote in his veto message. The 2019 bill died in the state Senate.

    Rodriguez said ERs have become more dangerous for health care workers since then and that “there has to be accountability” for violent behavior. Opponents fear stiffer penalties would be levied disproportionately on patients of color or those with developmental disabilities. They also point out that violent patients can already face penalties under existing assault and battery laws.

    Data from the California Division of Occupational Safety and Health shows that reported attacks on ER workers by patients, visitors, and strangers jumped about 25% from 2018 to 2023, from 2,587 to 3,238. The rate of attacks per 100,000 ER visits also increased.

    Punching, kicking, pushing, and similar aggression accounted for most of the attacks. Only a small number included weapons.

    These numbers are likely an undercount, said Al’ai Alvarez, an ER doctor and clinical associate professor at Stanford University’s Department of Emergency Medicine. Many hospital staffers don’t fill out workplace violence reports because they don’t have time or feel nothing will come of it, he said.

    Ravera remembers when her community rallied around health care workers at the start of the pandemic, acting respectfully and bringing food and extra N95 masks to workers.

    “Then something just switched,” she said. “The patients became angrier and more aggressive.”

    Violence can contribute to burnout and drive workers to quit — or worse, said Alvarez, who has lost colleagues to suicide, and thinks burnout was a key factor. “The cost of burnout is more than just loss of productivity,” he said. “It’s loss of human beings that also had the potential to take care of many more people.”

    The National Center for Health Workforce Analysis projects California will experience an 18% shortage of all types of nurses in 2035, the third worst in the country.

    Federal legislation called the Safety From Violence for Healthcare Employees Act would set sentences of up to 10 years for assault against a health care worker, not limited to emergency workers, and up to 20 years in cases involving dangerous weapons or bodily injury. Though it was introduced in 2023, it has not yet had a committee hearing.

    Opponents of the California bill, which include ACLU California Action, the California Public Defenders Association, and advocates for people with autism, argue it wouldn’t deter attacks — and would unfairly target certain patients.

    “There’s no evidence to suggest that increased penalties are going to meaningfully address this conduct,” said Eric Henderson, a legislative advocate for ACLU California Action. “Most importantly, there are already laws on the books to address assaultive conduct.”

    Beth Burt, executive director of the Autism Society Inland Empire, said the measure doesn’t take into account the special needs of people with autism and other developmental disorders.

    The smells, lights, textures, and crowds in the ER can overstimulate a person with autism, she said. When that happens, they can struggle to articulate their feelings, which can result in a violent outburst, “whether it’s a 9-year-old or a 29-year-old,” Burt said.

    She worries that hospital staff may misunderstand these reactions, and involve law enforcement when it’s not necessary. As “a parent, it is still my worst fear” that she’ll get a phone call to inform her that her adult son with autism has been arrested, she said.

    Burt would rather the state prioritize de-escalation programs over penalties, such as the training programs for first responders she helped create through the Autism Society Inland Empire. After implementing the training, hospital administrators asked Burt to share some strategies with them, she said. Hospital security staffers who do not want to use physical restraints on autistic patients have also sought her advice, she said.

    Supporters of the bill, including health care and law enforcement groups, counter that people with mental health conditions or autism who are charged with assault in an ER may be eligible for existing programs that provide mental health treatment in lieu of a criminal sentence.

    Stephanie Jensen, an ER nurse and head of governmental affairs for the Emergency Nurses Association, California State Council, said her organization is simply arguing for equity. “If you punch me in the hospital, it’s the same as if you punch me on the street,” she said.

    If lawmakers don’t act, she warned, there won’t be enough workers for the patients who need them.

    “It’s hard to keep those human resources accessible when it just seems like you’re showing up to get beat up every day,” Jensen said. “The emergency department is taking it on the chin, literally and figuratively.”

    This article was produced by KFF Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. 




    Kaiser Health NewsThis article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

    [ad_2]

    Source link

  • Household chemicals endanger brain’s myelin-forming cells

    Household chemicals endanger brain’s myelin-forming cells

    [ad_1]

    In a recent study published in the journal Nature Neuroscience, researchers in the United States pinpointed and evaluated environmental chemicals that hinder oligodendrocyte development through varied mechanisms, assessing their neurodevelopmental impacts.

    Study: Pervasive environmental chemicals impair oligodendrocyte development. Image Credit: Lightspring / ShutterstockStudy: Pervasive environmental chemicals impair oligodendrocyte development. Image Credit: Lightspring / Shutterstock

    Background 

    Human exposure to environmental chemicals, especially during the critical developmental stages of children’s central nervous systems, raises significant health concerns. Substances like methylmercury, lead, and polychlorinated biphenyls are linked to disrupting brain development, potentially contributing to the increasing prevalence of neurodevelopmental disorders such as autism and Attention-Deficit/Hyperactivity Disorder (ADHD). These trends suggest that environmental factors play a critical role beyond genetics. Oligodendrocytes, vital for brain functionality through myelination and neuronal support, are particularly susceptible to these chemicals from fetal development into adolescence. Despite their significance, limited research has focused on the impact of environmental toxins on oligodendrocytes. This gap highlights the need for further investigation into how these chemicals affect oligodendrocyte development and identifying ways to counteract their detrimental effects on neurodevelopment.

    About the study 

    The present study adhered to ethical standards set by the International Society for Stem Cell Research and the National Institutes of Health, receiving approval from the Case Western Reserve University Institutional Animal Care and Use Committee. Mouse oligodendrocyte precursor cells (OPCs) were cultured from induced pluripotent stem cells (iPSCs), following established protocols that involved removing iPSCs from a feeder layer, dissociating them, and then cultivating them in a medium conducive to OPC expansion and maturation. The culture medium was switched on the tenth day to promote OPC development, utilizing a specific combination of supplements to enrich OPC populations. Additionally, primary mouse OPCs and astrocytes were derived from dissected mouse brain tissue, with the cells undergoing culture in specially prepared media to encourage the growth of OPCs and astrocytes, respectively.

    Human cortical organoids were generated from embryonic stem cells and iPSCs, following rigorous stem cell research guidelines. These organoids were cultured in a medium optimized for OPC expansion and differentiation, incorporating various growth factors and supplements. Chemical screening on OPCs utilized the United States Environmental Protection Agency (US EPA) Toxicity Forecaster chemical library to identify compounds that disrupt OPC development. 

    Various methods, including immunocytochemistry, high-content imaging, and cell viability assays, were employed to assess the impact of chemicals on OPCs. Additionally, the study explored the effects of specific quaternary compounds on cell viability, employing a range of experimental setups across different cell types to understand the compounds’ toxicity profiles. 

    Study results 

    The present study developed a high-throughput screening method to assess the impact of environmental chemicals on the development of mouse pluripotent stem cells (mPSCs)- derived OPCs into oligodendrocytes. Among the 1,823 chemicals screened, a selection was found to either be cytotoxic to developing oligodendrocytes or impede their generation without inducing cytotoxicity. The screening revealed that a majority of the chemicals had no significant effect on oligodendrocyte development or viability, yet 292 were identified as cytotoxic and 47 as inhibitors of oligodendrocyte generation.

    Further investigation using the MTS assay, which measures metabolic activity as an indicator of cell viability, validated the cytotoxic effects of certain chemicals. Comparison of cytotoxicity profiles across different cell types, including mouse astrocytes and data from the US EPA, identified quaternary compounds as selectively cytotoxic to oligodendrocytes. These compounds, characterized by a central nitrogen with four alkyl groups, demonstrated a specific toxicological sensitivity in developing oligodendrocytes. The study also explored the activation of the integrated stress response (ISR) as a potential mechanism for the cytotoxicity induced by quaternary compounds.

    Quaternary compounds were also tested for their ability to cross the blood-brain barrier and were found to be present in brain tissue at nanomolar concentrations following administration to mice. Furthermore, the study extended to human pluripotent stem cell-derived regionalized neural organoid models, confirming that quaternary compounds could disrupt human oligodendrocyte development, reducing the density of SOX10+ OPCs and oligodendrocytes.

    Additionally, the screening identified organophosphate flame retardants as inhibitors of oligodendrocyte development. These compounds were shown to arrest the progression of early to intermediate and mature oligodendrocytes. The study’s findings were extended to in vivo and in vitro models of human brain development, demonstrating that exposure to organophosphate flame retardants, particularly Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), significantly reduced the number of SOX10+CC1+ oligodendrocytes in both mouse and human models.

    Lastly, the study utilized data from the National Health and Nutrition Examination Survey (NHANES) to investigate associations between exposure to organophosphate flame retardants and neurodevelopmental outcomes in children. High levels of urinary Bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), a metabolite indicative of TDCIPP exposure, were associated with an increased likelihood of special education needs and gross motor dysfunction, suggesting a strong link between organophosphate flame retardant exposure and adverse neurodevelopmental outcomes. 

    [ad_2]

    Source link

  • Prenatal topiramate exposure not associated with increased autism risk among children

    Prenatal topiramate exposure not associated with increased autism risk among children

    [ad_1]

    Topiramate—an antiseizure medication prescribed to treat epilepsy as well as migraines and bipolar disorder—does not appear to increase the risk of autism spectrum disorder (ASD) among children exposed to it prenatally, according to a new study led by Harvard T.H. Chan School of Public Health.

    The study was published online on March 20, 2024, in the New England Journal of Medicine.

    Many studies have examined the neurodevelopmental impacts of prenatal exposure to valproate and lamotrigine, two other antiseizure medications commonly taken by people living with epilepsy. Most of these studies have linked valproate to a heightened risk of ASD among children exposed to it prenatally but have found no additional risk linked to lamotrigine. Research into the neurodevelopmental safety of topiramate, meanwhile, has been limited, with mixed findings.

    Our findings provide needed clarity on the possible neurodevelopmental impacts of this commonly used drug. While our primary analyses focused on mothers with epilepsy, the study has implications for moms and moms-to-be who live with other conditions treated by topiramate as well.”


    Sonia Hernández-Díaz, lead author, professor of epidemiology

    Using data recorded between 2000 and 2020 across two U.S. health care databases, the researchers identified a population-based cohort of nearly 4.3 million pregnant women and their children. Children who had been exposed to topiramate during the second half of pregnancy were compared with children who had never been exposed to an antiseizure medication prenatally, with respect to the risk of ASD. Children who had been exposed to valproate and lamotrigine during the second half of pregnancy were used as control groups.

    The study found that at age 8, children born to mothers with epilepsy had a higher prevalence of ASD compared to children in the general population. Within the full study population, 1.9% of children who had never been prenatally exposed to an antiseizure medication were diagnosed with ASD. For children born to mothers with epilepsy, the incidence was 4.2% with no exposure to an antiseizure medication; 6.2% with exposure to topiramate; 10.5% with valproate; and 4.1% with lamotrigine. However, after adjusting for confounding variables, the researchers concluded that prenatal exposure to topiramate and lamotrigine was no longer associated with additional risk of developing ASD, while prenatal exposure to valproate remained associated with additional risk.

    The researchers noted that this relationship between valproate and ASD is dose-dependent, and that while topiramate appears safe from a neurodevelopmental standpoint, it remains linked with a higher risk of oral clefts. They also noted certain limitations of the study, including a substantial portion of children in the study population being lost to follow up before age 8.

    Krista Huybrechts, associate professor in the Department of Epidemiology, was also a co-author.

    The study was funded by the National Institute of Mental Health (grant R01MH116194).

    Source:

    Harvard T.H. Chan School of Public Health

    Journal reference:

    Hernández-Díaz, S., et al. (2024) Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure. New England Journal of Medicine. doi.org/10.1056/NEJMoa2309359.

    [ad_2]

    Source link

  • Antipsychotic use during pregnancy not linked to childhood neurodevelopmental disorders or learning difficulties

    Antipsychotic use during pregnancy not linked to childhood neurodevelopmental disorders or learning difficulties

    [ad_1]

    The use of antipsychotics during pregnancy isn’t linked to childhood neurodevelopmental disorders or learning difficulties, UNSW Sydney-led study shows – giving assurance to those concerned about continuing their medications during pregnancy. 

    Antipsychotics – a branch of medication designed to treat schizophrenia and bipolar disorder – are important tools for mental health care management. They work by blocking the effect of dopamine, which can help reduce psychotic symptoms such as hallucinations or delusions. 

    These versatile medications are also widely used for other mental health conditions and developmental disorders, like anxiety, depression, autism spectrum disorder, and insomnia. 

    But many women and pregnant people using these medications may feel concerned about the potential risks they pose to their unborn baby. 

    A new international study led by UNSW Sydney, published today in eClinicalMedicine, tracked the long-term risk of a child developing neurodevelopmental disorders and learning difficulties after being exposed to antipsychotics in the womb. 

    The findings show there’s little to no increased risk of the exposure leading to intellectual disability, poor academic performance in maths and language, or learning, speech and language disorders. 

    The findings are really reassuring for both women managing these psychiatric conditions during pregnancy and their providers.”


    Dr. Claudia Bruno, pharmacoepidemiologist at UNSW’s School of Population Health and lead author of the study

    “There’s no increased risk when taking the medication during pregnancy, not only for the specific neurodevelopmental disorders that we looked at, but also ADHD and autism as shown in our team’s previous studies.” 

    This research is the most comprehensive study on antipsychotics and neurodevelopmental outcomes to date: it pulls together nationwide data from Denmark, Finland, Iceland, Norway, and Sweden into a large sample size of 213,302 children born to mothers with a diagnosed psychiatric condition, 5.5 per cent (11,626) of which were prenatally exposed to antipsychotics. 

    These five Nordic countries all have similar health and education systems and keep detailed data on birth records, filled prescriptions, and diagnoses from inpatient and outpatient specialist care, as well as antenatal care. The researchers teamed these data with results from the children’s first standardised national school test (similar to Australia’s NAPLAN tests), which happens between the ages of 8-10. 

    “It’s reassuring that everything points to the same ‘no major indication’ of increased risks overall,” says Scientia Associate Professor Helga Zoega, senior author of the study and pharmacoepidemiologist, also based at UNSW’s School of Population Health. 

    “The study builds on our team’s previous work that looked at birth outcomes, including serious congenital malformations, where we’ve seen similar null results. 

    “I think it’s important to get excited about null results because this is essential information for the management of serious mental health conditions in pregnancy. It’s as equally important as finding an increased risk of outcomes.” 

    A gap that big health data is trying to fix 

    While this study is part of a growing body of research about medication safety in pregnancy, there’s still a lot left in this field to discover, says A/Prof. Zoega. 

    “This is a hugely understudied area,” she says. “Unfortunately, we know way too little about medication safety during pregnancy.” 

    One of the reasons so little is known about medicines and pregnancy is that it’s simply not feasible – or in many cases, ethical – to conduct randomised clinical trials on pregnant women. The potential risks of testing or withholding treatment to the unborn child and mother or pregnant person is often too great. 

    That’s where harnessing big data can step in – although the research isn’t as simple as looking at the raw data alone. 

    For example, women treated with antipsychotics during pregnancy were more likely to smoke, have higher BMIs, lower education levels, to be older (35 years or more) and use other medications during pregnancy compared to women who didn’t take antipsychotics during pregnancy – all of which are risk factors that can potentially impact birth outcomes. 

    These circumstances – called ‘confounding factors’ – are accounted for in observational research using careful study design and complex adjusted risk models to make sure the results show the impact of the medication alone. 

    “These types of studies are methodologically tricky, and can take a long time to do,” says A/Prof. Zoega. “This study has been in the making for almost 10 years now. 

    “We already know these women are dealing with psychiatric conditions, and by genetic default, their children would be more likely to have psychiatric or neurodevelopmental outcomes. But we’re focused on the risks and benefits of the medication treatment in pregnancy, so we use methods to make the comparison groups as similar as possible.” 

    The researchers also strengthened their findings by slicing up the data to take a closer look at whether individual medications, trimesters of exposure, and siblings carried higher risk levels. 

    While one antipsychotic, chlorpromazine, showed potential increased links to language and speech delays, these findings were based on small sample sizes of 8-15 children, so more research is needed to investigate this potential link. 

    Other than this anomaly, the results supported the finding that there was little to no increased risk of children prenatally exposed to antipsychotics developing neurodevelopmental disorders or learning difficulties. 

    Looking ahead 

    Dr Bruno is currently involved in two related studies on prenatal medication use and pregnancy outcomes. One explores if there is a relationship between the use of antiseizure medications during pregnancy and child school performance, and the other examines whether taking ADHD medication use and discontinuation during pregnancy on child health outcomes. 

    But she sees many avenues for future research to build on this work, including harnessing more Australian big health data. 

    “There’s so much to learn about medication safety in pregnancy,” says Dr Bruno. “These women are typically excluded from clinical trials, so there’s a real lack of data or evidence. 

    “While these results are highly generalisable to women in Australia, we now have real-world linked Australian data that can start contributing to large-scale international studies like this one which we’re very excited for.” 

    A/Prof. Zoega co-leads an international research collaboration called International Pregnancy Drug Safety Study (InPreSS), which investigates the safety of medication in pregnancy. She says there’s plenty to do in this space. 

    “Antipsychotics are only one class of medications, and we already know that up to 80 per cent of women use at least one prescription medicine during pregnancy. Most often, there’s little or no guidance on safety. 

    “There are so many unanswered questions that there’s enough for a lifetime of research.” 

    Source:

    University of New South Wales

    Journal reference:

    Bruno, C., et al. (2024) Antipsychotic use during pregnancy and risk of specific neurodevelopmental disorders and learning difficulties in children: a multinational cohort study. eClinicalMedicine. doi.org/10.1016/j.eclinm.2024.102531.

    [ad_2]

    Source link

  • Brain region associated with movement found to be abnormal in children with developmental language disorder

    Brain region associated with movement found to be abnormal in children with developmental language disorder

    [ad_1]

    A rigorous analysis of numerous studies concludes that a part of the brain traditionally associated with movement is abnormal in children with developmental language impairments, according to Georgetown University Medical Center neuroscientists. The discovery has the potential to improve both the diagnosis and treatment of the language difficulties.

    The researchers investigated brain abnormalities in developmental language disorder. This condition, which impacts the development of various aspects of language, is about as common as attention-deficit/hyperactivity disorder (ADHD) and dyslexia, and more prevalent than autism. The scientists found that abnormalities occurred specifically in the anterior neostriatum within the basal ganglia, a structure found deep in the brain. They describe their findings in Nature Human Behaviour on March 15.

    To better understand why the language impairments occur, the researchers analyzed the results of 22 articles examining brain structures in people with the disorder, and then employed a new computational method to identify common patterns of abnormalities across the studies. They determined that the anterior neostriatum was abnormal in 100% of the studies that examined the structure, with fewer abnormalities in all other parts of the brain.

    We hope that by identifying the neural bases of developmental language difficulties we may help increase awareness of a major, but also rather unrecognized, disorder. We caution, however, that further research is necessary to understand exactly how the anterior neostriatum might lead to the language difficulties.”


    Michael T. Ullman, PhD, study’s lead author, professor of neuroscience and director of the Brain and Language Laboratory at Georgetown University Medical Center

    Ullman says the findings underscore the potential utility of drugs that are known to improve movement impairments due to basal ganglia dysfunction, such as those that act on dopamine receptors. Interventions that encourage compensation by intact brain structures may also be useful. Additionally, basal ganglia abnormalities could potentially serve as early biomarkers of an increased likelihood of developmental language problems. Such early warning signs could trigger further diagnostic procedures, potentially leading to early therapy.

    “Continuing research efforts to further understand the neurobiology of developmental language disorder, especially the role of the basal ganglia, could help the many children who are affected by these problems,” concludes Ullman.

    In addition to Ullman, other authors at Georgetown include Mariel Pullman, Jarrett Lovelett, Xiong Jiang, and Peter Turkeltaub. Gillian Clark was at Deakin University, Melbourne, Australia. Elizabeth Pierpont is at the University of Minnesota Medical Center, Minneapolis.

    This work was supported by NIH grants R01 HD049347 and R21 HD 087088; NSF grants BCS 1439290 and BCS 1940980; and funding from the Mabel H. Flory Trust.

    The authors declare no personal financial interests related to the study.

    Source:

    Georgetown University Medical Center

    Journal reference:

    Ullman, M. T., et al. (2024). The neuroanatomy of developmental language disorder: a systematic review and meta-analysis. Nature Human Behaviour. doi.org/10.1038/s41562-024-01843-6.

    [ad_2]

    Source link

  • Study highlights growing burden of neurological disorders worldwide

    Study highlights growing burden of neurological disorders worldwide

    [ad_1]

    Globally, the number of people living with, or dying from, neurological conditions such as stroke, Alzheimer’s disease and other dementias, and meningitis has risen substantially over the past 30 years due to the growth and aging of the global population as well as increased exposure to environmental, metabolic, and lifestyle risk factors. In 2021, 3.4 billion people experienced a nervous system condition, according to a major new analysis from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, published in The Lancet Neurology journal.

    The analysis suggests that worldwide, the overall amount of disability, illness, and premature death-;a measurement known as disability-adjusted life years (DALYs)-;caused by neurological conditions increased by 18% over the past 31 years, rising from around 375 million years of healthy life lost in 1990 to 443 million years in 2021.

    The absolute number of DALYs is increasing in large part due to aging and growing populations worldwide. However, if the impact of demographics is removed through age-standardization, rates of DALYs and deaths caused by neurological conditions have declined by around a third (27% and 34% respectively) worldwide since 1990-;largely due to better awareness, vaccination, and global prevention efforts for some conditions such as tetanus (93% decrease in age-standardized rates of DALYs), meningitis (62% decrease), and stroke (39% decrease). 

    The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy (brain injury), migraine, Alzheimer’s disease and other dementias, diabetic neuropathy (nerve damage), meningitis, epilepsy, neurological complications from preterm birth, autism spectrum disorder, and nervous system cancers. Neurological consequences of COVID-19 (cognitive impairment and Guillain-Barré syndrome) ranked 20th, accounting for 2.48 million years of healthy life lost in 2021. 

    The most prevalent neurological disorders in 2021 were tension-type headaches (around 2 billion cases) and migraines (about 1.1 billion cases). Diabetic neuropathy is the fastest-growing of all neurological conditions.

    The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes.”


    Dr Liane Ong, co-senior author from the Institute for Health Metrics and Evaluation (IHME), University of Washington, USA

    The current study builds on previous GBD analyses [2] to provide the largest and most comprehensive analysis to compare the prevalence and burden (illness and death) of nervous system disorders between countries on a global scale between 1990 and 2021-;expanding the number of studied neurological conditions from 15 to 37 that span from birth to later life.

    To better reflect that neurological disorders can occur at any stage of life, for the first time the GBD 2021 Nervous System Disorders Collaborators studied neurodevelopmental disorders and neurological conditions in children, and found that they were responsible for almost a fifth (18%) of all DALYs in 2021, accounting for 80 million years of healthy life lost worldwide. 

    “Every country now has estimates of their neurological burden based on the best available evidence,” said lead author Dr Jaimie Steinmetz from IHME. “As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies.”

    The study, conducted to inform ongoing advocacy and awareness efforts, will support the WHO’s Intersectoral Global Action Plan on epilepsy and other neurological disorders 2022–2031 (IGAP) that aims to reduce the impact and burden of neurological disorders and improve the quality of life of people with neurological disorders as well as their caregivers and families.

    Over 80% of neurological deaths and health loss occur in low- and middle-income countries (LMICs)

    Overall, estimates reveal striking differences in nervous system burden between world regions and national income levels. In high-income Asia Pacific and Australasia – regions with the best neurological health – the rate of DALYs and deaths were under 3,000 and 65 per 100,000 people, respectively in 2021. In these regions, stroke, migraine, dementia, diabetic neuropathy, and autism spectrum disorders accounted for most health loss. 

    In contrast, in the worst-off regions of western and central sub-Saharan Africa, the rate of DALYs and deaths were up to five times higher (over 7,000 and 198 per 100,000 people respectively) in 2021, with stroke, neonatal encephalopathy (brain injury), dementia, and meningitis the biggest contributors to years of healthy life lost.

    “Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” said Dr. Tarun Dua, Unit Head of WHO’s Brain Health unit and one of the co-senior authors of the study. “Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries.”

    The authors highlight that, as of 2017, only a quarter of countries globally had a separate budget for neurological conditions, and only around half had clinical guidelines. What’s more, the medical personnel who care for people with neurological conditions are unevenly distributed around the world, with high-income countries having 70 times more neurological professionals per 100,000 individuals than LMICs.

    Prevention needs to be a top priority

    “Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” said co-lead author Dr Katrin Seeher, Mental Health Specialist at WHO’s Brain Health Unit. 

    The study quantified the proportion of nervous system burden that was potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability. 

    The analysis suggests that modifying 18 risk factors over a person’s lifetime-;most importantly high systolic blood pressure (57% of DALYs)-;could prevent 84% of global DALYs from stroke. 

    Additionally, estimates suggest that controlling lead exposure could reduce the burden of intellectual disability by 63%, while reducing high fasting plasma glucose to normal levels could reduce the burden of dementia by around 15%. 

    “The worldwide neurological burden is growing very fast and will put even more pressure on health systems in the coming decades,” said co-senior author Dr Valery Feigin, Director of Auckland University’s National Institute for Stroke and Applied Neuroscience in New Zealand. “Yet many current strategies for reducing neurological conditions have low effectiveness or are not sufficiently deployed, as is the case with some of the fastest-growing but largely preventable conditions like diabetic neuropathy and neonatal disorders. For many other conditions, there is no cure, underscoring the importance of greater investment and research into novel interventions and potentially modifiable risk factors.”

    “Nervous system conditions include infectious and vector-borne diseases and injuries as well as non-communicable diseases and injuries, demanding different strategies for prevention and treatment throughout life,” said Steinmetz “We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world.” 

    Despite these important findings, the authors note several limitations, including that, while they have done their best to capture all nervous system health loss, some conditions were left out because they could not isolate the neurological component, including infections such as HIV, which has a large impact in many parts of the world. And while the study uses the best available evidence, estimates are constrained by the quantity and quality of data, especially in LMICs.

    Writing in a linked Comment, Professor Wolfgang Grisold, President of the World Federation of Neurology, London, UK (who was not involved in the study) says, “This important new GBD report highlights that the burden of neurological conditions is greater than previously thought. In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging, because the effects on the individuals vary substantially.”

    Source:

    Journal reference:

    GBD 2021 Nervous System Disorders Collaborators. (2024). Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Neurology. doi.org/10.1016/s1474-4422(24)00038-3.

    [ad_2]

    Source link

  • Kobe University study identifies FAM81A as key player for synaptic function

    Kobe University study identifies FAM81A as key player for synaptic function

    [ad_1]

    A protein that appears in postsynaptic protein agglomerations has been found to be crucial to their formation. The Kobe University discovery identifies a new key player for synaptic function and sheds first light on its hitherto uncharacterized cellular role and evolution.

    What happens at the synapse, the connection between two neurons, is a key factor in brain function. The transmission of the signal from the presynaptic to the postsynaptic neuron is mediated by proteins and their imbalance can lead to neuropsychiatric conditions such as severe depression, autism, or alcohol dependence. However, due to the vast diversity of proteins present at this junction, many have not yet been studied and often it is not even clear whether those previously found actually belong there or whether they are just impurities resulting from the analysis process. A particularly conspicuous structure directly underneath the postsynaptic membrane is the so-called “postsynaptic density,” an agglomeration of possibly thousands of different proteins.

    To shed some light on the postsynaptic density, Kobe University neurophysiologist Takumi Toru and his group first compared 35 datasets of previous studies on the phenomenon to find out which uncharacterized proteins appear consistently.

    We established an analytical pipeline to unify and align protein structures in different datasets. This resulted in the identification of a poorly characterized synaptic protein that has been detected in more than 20 of these datasets.”

    Kaizuka Takeshi, first author of the paper

    This suggested that the protein, which goes by the label FAM81A, is probably relevant to the function of the whole structure, so the team analyzed its interactions with other proteins, its distribution in and around neurons and its effect on neuron shape and function, the mechanism of its function, and its evolution. In short, they gave this protein a full first characterization.

    Takumi summarizes their results, now published in the journal PLoS Biology, “The important finding is that FAM81A interacts with at least three major postsynaptic proteins and modulates their condensation. This suggests that FAM81A is a major regulatory factor in the postsynaptic density.” The group could confirm that FAM81A facilitates the condensation of key proteins into a membrane-less organelle through liquid-liquid phase separation, a process in which strongly interacting molecules exclude elements of the surrounding medium, and that the absence of the protein leads to a significant decrease of activity in cultured neurons.

    Humans have two related copies of the gene, FAM81A and FAM81B. However, while FAM81A is expressed in the brain, FAM81B is expressed only in the testes. Furthermore, birds and reptiles also have two copies of the gene, but amphibians, fish and invertebrates have only one, and its expression is not localized to one tissue. “Interestingly, it seems that the evolutionary conservation of FAM81A function in the synapse is limited compared to other synaptic molecules, as the FAM81A homolog in fish is not detected in the synapse. This suggests that FAM81A could be a key protein in understanding the cognitive functions of higher vertebrate brains,” says Kaizuka.

    But their work was only the first step. To really understand the role of the protein, it is necessary to study its function in the complex environment of the brain. The Kobe University research team thus wants to create mouse models that lack the gene for FAM81A and study what this means both for the function of the synapses and the behavior of the organism.

    Source:

    Journal reference:

    Kaizuka, T., et al. (2024) FAM81A is a postsynaptic protein that regulates the condensation of postsynaptic proteins via liquid–liquid phase separation. PLOS Biology. doi.org/10.1371/journal.pbio.3002006.

    [ad_2]

    Source link

  • Key brain cells linked to repetitive behaviors in psychiatric diseases

    Key brain cells linked to repetitive behaviors in psychiatric diseases

    [ad_1]

    In a recent Nature study, researchers discovered that Crym-expressing astrocytes in the central striatum play a key role in the manifestation of repetitive behaviors associated with many neuropsychiatric diseases, thus demonstrating its potential as a therapeutic target.

    Study: Crym-positive striatal astrocytes gate perseverative behavior. Image Credit: Vitaly Sosnovskiy / Shutterstock.com

    What are astrocytes?

    Astrocytes are dominant glial cells within the central nervous system (CNS) and interact with other neurons to exert various metabolic, neuroprotective, structural, and homeostatic properties. Astrocytes exhibit different properties that are unique to their specific location within the brain; however, it remains unclear how specialized astrocytes function in their associated neural circuits and how these activities contribute to normal physiology and behavior, as well as the development of certain neurological diseases.  

    The basal ganglia houses the striatum, which consists of astrocytes that highly express the Crym gene. Crym encodes µ-crystallin, a cytosolic protein that has been reported to function as a ketamine reductase or bind to nicotinamide adenine dinucleotide phosphate (NADPH) to regulate the thyroid hormone T3.

    Previous studies have shown that Crym expression may be associated with amyotrophic lateral sclerosis (ALS), schizophrenia, and Huntington’s disease (HD). Nevertheless, there remains a lack of data on the precise role of Crym in striatal astrocytes and the function of µ-crystallin within the brain.

    The localization of Crym and µ-crystallin

    Striatum samples were originally obtained from individuals diagnosed with obsessive compulsive disorder (OCD) or HD to identify enriched genes present within striatal astrocytes. As compared to control tissues, CRYM was downregulated to about 40% within the caudate nucleus in both OCD and HD samples. Likewise, mouse models of HD have demonstrated that CRYM is among the top 4% of downregulated genes, thus indicating the crucial role of this gene in HD pathology.

    These observations subsequently led to in vivo studies, in which Crym expression was dominant within the striatum, with µ-crystallin-expressing astrocytes accounting for about 49% of astrocytes within this region of the brain. More specifically, µ-crystallin expression was particularly high within the subventricular zone (SVZ), thus confirming that Crym expression may be anatomically allocated to a specific population of striatal astrocytes.  

    Investigating the effects of Crym loss-of-function

    To elucidate the role of the Crym gene, the researchers developed six Crym knockout (KO) mouse strains using the clustered regularly interspaced palindromic repeats (CRISPR)-Cas9 single-guide ribonucleic acids (sgRNAs) that were delivered through adeno-associated virus (AAV) intracranial administration, three of which were ultimately selected due to their superior KO efficiency.

    Three weeks after AAV administration, µ-crystallin levels within astrocytes declined by 80%, except for those present in the SVZ. Although Crym KO did not cause any significant weight loss or behavioral effects in the open-field, footprint, and rotarod tests, these mice had a shorter latency to start and longer digging durations in the marble-burying test. Longer self-grooming and water bottle lick durations were also observed in Crym KO mice.

    Crym KO mice also spent more time with a familiar object in the novel object recognition task, which may indication perseveration for that object. These perseverative behaviors observed in Crym KO mice can be correlated with those associated with certain psychiatric and neurological disorders including OCD, HD, Tourette’s syndrome, autism, and suicide-associated perseveration in HD.

    Furthermore, Crym KO mice exhibited an increased concentration of cFOS+ neurons, which is a marker for increased neuronal activity, within the lateral orbitofrontal cortex (IOFC), central striatum, and dorsal thalamus (dTH). IOFC striatal projections were found to invade the central striatum that exhibited high levels of Crym+ neurons, an observation that has been previously implicated in OCD.

    Crym mechanism of action

    Gas chromatography-mass spectrometry (GC-MS) was used to compare the glutamate/gamma-aminobutyric acid (GABA) ratio in Crym KO and control striatal samples. As compared to control mice, the glutamate/GABA ratio was significantly higher in Crym KO mice, which indicates greater release of glutamate from IOFC projections.

    A significant reduction of GABA and monoamine oxidase B (MOAB), the latter of which is an astrocytic enzyme that produces GABA, was also observed in Crym KO mice. These observations suggest that increased synaptic excitation from IOFC terminals leads to lower levels of tonic GABA, which causes reduced presynaptic inhibition.

    Study significance

    Crym-expressing astrocytes in the central striatum regulate the release of GABA from the IOFC into the central striatum. Importantly, the loss of this regulation can lead to perseveration, which involves the continuation or repetition of a response or activity, a phenotype that is often reported in OCD, autism, Tourette’s syndrome, and HD.  

    These findings provide guidance for the development of future therapeutic strategies that can target the release of neurotransmitters from IOFC terminals projecting into the central striatum. Furthermore, the identification of brain region-enriched astrocytes can also support future studies aiming to identify specific circuits and nuclei involved in different neurological diseases.

    Journal reference:

    • Ollivier, M., Soto, J. S., Linker, K. E., et al. (2024). Crym-positive striatal astrocytes gate perseverative behaviour. Nature. doi:10.1038/s41586-024-07138-0

    [ad_2]

    Source link

  • Prenatal exposure to nicotine could increase risk of behavioral disorders in newborns, study finds

    Prenatal exposure to nicotine could increase risk of behavioral disorders in newborns, study finds

    [ad_1]

    Although several studies have linked smoking during pregnancy with neurodevelopmental disorders, the results of behavioral experiments in mice prenatally exposed to nicotine have been inconsistent. In a recent study, scientists from Japan developed a deep learning-based framework to automatically observe and classify mice behavior in such experiments, producing more accurate and unbiased results. They show that prenatal exposure to nicotine could increase the risk of autism spectrum- and attention deficit/hyperactivity disorders in newborns.

    The fact that smoking is a risk factor for several diseases, including cancer, stroke, and diabetes, has been known for approximately half a century. However, over the past few decades, scientists have brought to light many of the detrimental effects of smoking during pregnancy, linking this habit to high infant mortality, failed delivery, and low body weight at birth. In addition, recent studies suggest that prenatal nicotine exposure (PNE) may be related to neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

    For a long time now, scientists have used animal models (like rodents) to understand how PNE leads to neurodevelopmental disorders. By carefully analyzing the behavior of rodents, they can infer whether PNE is causing neurological changes and the brain regions affected by it; this can later be confirmed through histological analyses.

    Unfortunately, thus far, studies on behavioral changes induced by PNE in mice have shown varied results, some of which are contradictory. Although there could be multiple reasons behind these discrepancies, human error and bias are prime suspects. In general, the assessment of complex animal behaviors, especially social interactions, relies on the efforts of human observers, which introduces a baseline level of subjectivity that is hard to dispel. But what if we can leverage artificial intelligence (AI) to produce more accurate and unbiased results from observations of PNE mice behavior?

    In a recent study published in Cells on 1 February 2024, researchers from the Department of Molecular and Cellular Physiology at the Shinshu University School of Medicine, including graduate student Mengyun Zhou, Assistant Professor Takuma Mori, and Professor Katsuhiko Tabuchi, developed and trained a deep learning-based system to automatically analyze footage from behavioral experiments on mice. They used this tool to explore the behavioral changes induced by PNE in mice without observer biases, seeking to shed light on the link between nicotine and neurodevelopmental disorders.

    The proposed AI-based framework relied on a combination of two well-established open-source toolkits, namely DeepLabCut and Simple Behavioral Analysis (SimBA). “AI tools can label the body parts of animals in a markerless video footage and precisely estimate their poses using supervised machine learning,” explains Prof. Tabuchi. “Since animal behaviors are defined as a specific arrangement of body parts over a short period of time, deep-learning toolkits like SimBA can use the pose estimations obtained with DeepLabCut to classify different types of animal behaviors.” 

    After reaching an optimal training protocol for their framework using manually labeled data, the researchers conducted several experiments using PNE and control mice, looking for indicators of ADHD- and ASD-like behaviors. First, they carried out cliff avoidance reaction tests, which are used to test impulsivity. In these tests, they placed the subject mouse on top of a slightly elevated platform and took note-;both manually and with the AI system-;of how long the mouse waited before jumping down the platform. The test results suggested that PNE mice are more impulsive, a behavioral feature of ADHD in humans.

    They also tested the working memory of mice using a Y-shaped maze and counted the number of times each mouse spontaneously switched from one arm of the maze to another. “We observed a decrease in the spontaneous alteration in PNE mice, suggesting that their working memory was altered, which is another behavioral feature of ADHD,” comments Mengyun Zhou. “These results suggest prenatal exposure to nicotine may cause ADHD in mice, which is consistent with clinical reports in humans.“

    Finally, the researchers conducted open-field and social-interaction experiments, which represented the main challenge for their AI-based system. In these experiments, the researchers observed either one or two mice behaving freely in a large enclosure and looked for indicators of anxiety and social behaviors, such as grooming and following. Interestingly, PNE mice exhibited social behavioral deficits and increased anxiety which are features of ASD. Subsequent histological analysis of hippocampal brain tissue confirmed decreased neurogenesis, a hallmark of ASD. Thus, it appears that smoking may not only increase the risk of ADHD, but also ASD.

    Worth noting, the results obtained using the AI-based system were highly reliable, as Prof. Tabuchi highlights: “We validated the accuracy of our behavioral analysis framework by drawing a careful comparison between the results generated by the model and behavior assessments made by multiple human annotators, which is considered the gold standard.” These analyses cement the potential of the proposed approach and showcase its capabilities for many types of behavioral studies.

    With any luck, further efforts will pave the way to a solid understanding of mechanisms behind neurodevelopmental disorders like ASD and ADHD, ultimately leading to better diagnostic tools and therapeutic methods.

    Source:

    Journal reference:

    Zhou, M., et al. (2024). Deep-Learning-Based Analysis Reveals a Social Behavior Deficit in Mice Exposed Prenatally to Nicotine. Cells. doi.org/10.3390/cells13030275.

    [ad_2]

    Source link

  • Unlocking the molecular mysteries of autism and intellectual disability

    Unlocking the molecular mysteries of autism and intellectual disability

    [ad_1]

    A new study from a team of McGill University and Vanderbilt University researchers is shedding light on our understanding of the molecular origins of some forms of autism and intellectual disability.

    For the first time, researchers were able to successfully capture atomic resolution images of the fast-moving ionotropic glutamate receptor (iGluR) as it transports calcium. iGluRs and their ability to transport calcium are vitally important for many brain functions such as vision or other information coming from sensory organs. Calcium also brings about changes in the signaling capacity of iGluRs and nerve connections which are a key cellular events that lead to our ability to learn new skills and form memories.

    iGluRs are also key players in brain development and their dysfunction through genetic mutations has been shown to give rise to some forms of autism and intellectual disability. However, basic questions about how iGluRs trigger biochemical changes in the brain’s physiology by transporting calcium have remained poorly understood.

    In the study, the researchers took millions of snapshots of the iGluR protein in the act of transporting calcium, and unexpectedly discovered a temporary pocket that traps calcium on the outside of the protein. With this information at hand, they then used high-resolution electrophysiological recordings to watch the protein in motion as it transported calcium into the nerve cell.

    “The results are important because we describe for the first time the mechanism by which calcium is transported, which ultimately drives the cellular processes that lead to learning and memory,” said Derek Bowie, McGill’s lead author of the study, published in Nature Structural and Molecular Biology and co-Director of the Cell Information Systems group in the School of Biomedical Sciences.

    The biological mechanism discovered is not only conserved amongst all species of mammals, but is also found in organisms that branched away from the evolutionary pathway of humans more than 500 million years ago.

    The original blueprint of the protein design was so good it seems that evolution did not need to change it.”

    Derek Bowie, McGill’s lead author of the study

    “Visualizing the tiny ions and water molecules in the channel pore using cryo-EM technology was quite an amazing experience. It highlighted an ancient calcium binding pocket which we were able to understand further from a functional perspective in collaboration with Bowie Lab. Our finding is fundamental to calcium signaling in neurons and raises interesting hypotheses about synaptic function that could be tested by experiments in the future,” said Nakagawa, Vanderbilt’s lead author and Professor at the Department of Molecular Physiology and Biophysics at the School of Medicine Basic Sciences.

    Source:

    Journal reference:

    Nakagawa, T., et al. (2024). The open gate of the AMPA receptor forms a Ca2+ binding site critical in regulating ion transport. Nature Structural & Molecular Biology. doi.org/10.1038/s41594-024-01228-3.

    [ad_2]

    Source link