Heart Septal Defects

An analysis of how brains with different forms of autism develop has revealed common underlying mechanisms that may respond to existing medications. An analysis of how brains with different forms of autism develop has revealed common underlying mechanisms that may respond to existing medications. For the study, Rutgers Health researchers used a technique called induced pluripotent stem cells to transform the blood cells of people with both genetic and unexplained (or idiopathic) autism spectrum disorder (ASD) into early brain cells called neural precursor cells. As the precursor cells from both groups matured in the lab, defects in a common signaling pathway that controls structural proteins led them to struggle with an important step in cell differentiation, the growth of neurites, and the cell migration needed for proper brain architecture. Although some cell lines exhibited too much activity in this mTOR pathway, while others exhibited too little, the researchers could correct both problems and spur better cell differentiation with existing drugs that either stimulate or inhibit the activity of mTOR (mechanistic target of rapamycin). "Cells in a dish are not fully human cells that have developed in a fetus and functioned in a person, but they are a lot closer than mouse cells," said Emanuel DiCicco-Bloom, a professor of neuroscience and cell biology/pediatrics at Robert Wood Johnson Medical School and senior author of the study in eLife. "This finding is particularly interesting because the process of growing new synaptic spines when people learn things is completely analogous to the processes we observed in the cells we used for this experiment: growing axons and migrating during fetal development," DiCicco-Bloom said. "So even though this experiment mimicked a process you'd see during early to mid-pregnancy, the same process involving structural proteins is happening right now in you and me, which means that if we took cells from people with autism and found this abnormal regulation of mTOR in their cells in a dish, those people might be candidates as adults for mTOR regulating drugs to improve their function." The visible symptoms of ASD vary widely but typically feature some repetitive behaviors and some impairment in communication and social interaction. The condition's incidence has increased from about 1 in 150 children in 2000 to 1 in 36 children in 2020, according to the Centers for Disease Control and Prevention. Roughly 10 to 15 percent of people with ASD have genes that are known to elevate their risk for ASD. Other cases are idiopathic, meaning they are unexplained. Rutgers Health researchers began the study with blood from three unrelated people with idiopathic ASD, ages 4 to 14 years, with the expectation of finding person-specific differences in the processes occurring during development in utero. When the researchers used the pluripotent stem cell technique to transform blood cells into the sort of neuron precursors typically found in fetal brains, they unexpectedly found many similarities, including abnormalities in the mTOR pathway, which regulates cell creation, metabolism, neurite growth, remodeling and destruction, among many other functions. The researchers then gained access to blood cells from another three patients with ASD caused by a particular genetic abnormality associated with about 1 percent of ASD, deletion of genes on chromosome 16, called 16p11.2 deletion. They performed the same experiment and found the same disruptions in neuron development. Subsequent analysis showed that the mTOR signaling disruptions in some patients stemmed from excessive amounts of a particular molecule, while the disruptions in others stemmed from insufficient amounts. In either case, the researchers could use existing medications approved for use in other conditions to correct the problem and stimulate normal development. The study team has already begun a follow-up investigation to see if people with ASD stemming from other genetic causes exhibit similar disruptions in mTOR activity during development. If mTOR signaling disruption proves a common feature of ASD, tests of mTOR function could help clinicians diagnose the condition more accurately and differentiate it from other conditions with similar effects. "A couple of very rare genetic types of autism have already been linked to the mTOR pathway, but this is the first to connect mTOR with genes in the 16p11.2 area, which does not have mTOR on it, and with three presumably different types of idiopathic autism from three unrelated people," said Smrithi Prem, lead author of the study and a psychiatry resident at Penn Medicine who led the study as an MD/PhD student at Robert Wood Johnson Medical School. "These findings also echo something that has appeared in studies of other conditions, that not all people with mTOR dysregulation have excessive activation that needs inhibition," Prem said. "There are two kinds of mTOR dysregulation, but most trials we've run on people with mTOR dysregulation have only used inhibitors. Our findings showed that cells from two of the people we studied needed more mTOR, not less, and that may spur trials that give different types of mTOR treatment to different individual patients."

A new analysis involving over 13,000 people has found changes to blood vessels in the brain that can increase the risk of stroke and dementia are common in people with a range of heart conditions, regardless of whether they have experienced a stroke. A new analysis involving over 13,000 people has found changes to blood vessels in the brain that can increase the risk of stroke and dementia are common in people with a range of heart conditions, regardless of whether they have experienced a stroke. The new research, published today in Neurology®, the medical journal of the American Academy of Neurology, is the most comprehensive systematic review of 'hidden' brain changes in people with a range of heart conditions to date. Lead author Dr Zien Zhou from The George Institute for Global Health said that identifying these changes could play an important role in choosing treatments for these patients. "Although people with heart disease are two to three times more likely than the general population to have changes in their brain's vascular system, they're often overlooked, because these patients don't routinely undergo brain imaging unless they have suffered a stroke," he said. "But it can make them more susceptible to the risk of brain bleeds from medications commonly used to treat or prevent blood clots -- intracranial hemorrhage is a life-threatening complication with no proven treatment and a survival rate of less than 50 percent." Changes to blood vessels in the brain that can only be detected by brain imaging such as silent brain infarction (SBI) and cerebral small vessel disease (CSVD) are known to occur more commonly in older people or those who have hypertension. While not sufficient to cause obvious neurological symptoms, they can result in subtle neurological deficits and increase the longer-term risk of stroke or dementia. To determine the prevalence of these hidden or covert cerebrovascular changes in adults with atrial fibrillation, coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (a hole in the heart), George Institute researchers conducted a meta-analysis of 221 observational studies published between 1988 and 2022. The findings showed that in people with heart disease: The prevalence of these brain changes was generally the same between those with and without a recent stroke and there were no apparent sex differences in the results. Dr Zhou said the study also confirmed that heart disease is one of the main causes of these changes that reflect brain 'frailty'. "While several potential mechanisms of the association between heart disease and hidden cerebrovascular injury have been proposed, the two conditions share common risk factors such as ageing, hypertension, type 2 diabetes, hyperlipidaemia, and smoking," said Dr Zhou. "It's possible that a gradual decline in cardiac output in some patients with heart disease might affect how much blood is reaching the brain tissue, contributing to vascular changes and cognitive dysfunction in these patients," he added. "It's also possible that hidden brain changes and cognitive dysfunction are a consequence of tiny blood clots traveling to the brain through the arterial circulation after forming in the heart." Dr Zhou said that more research was needed to look at the exact causes of these brain changes and the implications for managing these patients. "We need to know whether performing an additional MRI in those considered for anticoagulation therapy -- which is required for most people with heart disease -- would be cost-effective in terms of preventing unwanted side effects," he said. "But refining the risks of brain clots and bleeds from anticoagulants and using this information to make the best treatment choice could improve treatment safety for people with heart disease."

World’s first legal exporters of psilocybin solidifies partnership with acclaimed university in Canada for preclinical studiesRUNAWAY BAY, Jamaica, March 21, 2024 (GLOBE NEWSWIRE) -- Rose Hill (or the “Company”), a premium psilocybin cultivator and supplier in Jamaica, announced today a strategic research partnership with the esteemed University of Guelph. This collaboration marks a significant milestone for both entities as they embark on a pioneering exploration of the potential benefits of psilocybin to address autism in the adolescent brain, the first-of-its-kind partnership in this space. The collaborative preclinical research will focus on exploring and standardizing the chemical diversity of Rose Hill’s psilocybin mushrooms, legally imported from Jamaica to Canada for the work. Additionally, utilizing a rodent model, the study will investigate their potential application in Autism Spectrum Disorders (ASD). “This collaboration is a testament to our unwavering commitment to propel crucial research on the transformative potential of psilocybin, seeking breakthroughs in treating conditions that still lack efficient solutions,” said Domenic Suppa, Co-founder and Chief Operations Officer of Rose Hill. “Our exploration of psilocybin's clinical applications for adolescents with ASD highlights our dedication to supplying reliable and potent mushrooms for both research endeavors and therapeutic innovations." The initial research, performed by Dr. Max Jones, Associate Professor of Plant Agriculture at the University of Guelph, will be dedicated to delving into the intricacies of Rose Hill's psilocybin mushrooms, with a primary emphasis on both exploring and standardizing their chemical diversity. Psilocybin mushrooms, known for their psychoactive properties, have long captivated the scientific community's interest due to their potential therapeutic applications and unique biochemical composition. By systematically investigating the chemical diversity within these mushrooms over the course of twelve months, the research aims to unravel the various compounds present and their potential implications. Standardization is a crucial aspect of this exploration, ensuring a consistent and reproducible understanding of the mushroom's chemical profile. This comprehensive study not only contributes to advancing the knowledge of these intriguing fungi but also lays the foundation for potential therapeutic developments and responsible usage within the field of neuropsychopharmacology. This translational neuroscience work, led by Dr. Melissa Perreault, an Associate Professor in the Department of Biomedical Sciences at the University of Guelph, will then explore the application of psilocybin in the adolescent brain using a rodent model widely used to study idiopathic ASD. In these studies, her team will examine the biological effects of oral microdose psilocybin mushroom administration, utilizing brain systems functional assays and a range of behavioral paradigms such as learning and memory, anxiety, social interactions, and repetitive behavior. Since its establishment in 2015, Rose Hill has consistently been at the forefront of research efforts and has become a key supplier of premier psilocybin biomass to esteemed research institutions globally. One of Rose Hill's notable achievements was securing Health Canada's approval for the first legal export of psilocybin from Jamaica to Canada. This certification allowed Rose Hill to provide exclusive, proprietary psilocybin biomass to a distinguished Canadian researcher and a leading provider of psychedelic-assisted therapies for eligible patients. The University of Guelph, with its Office of Research overseeing a $187 million research enterprise across seven colleges, has chosen Rose Hill as a partner for its expertise in mushroom cultivation and a proven record in delivering high-quality psilocybin products. "We chose to collaborate with Rose Hill due to their years of expertise in mushroom cultivation and strain development,” said Dr. Max Jones. “Their commitment to excellence and innovation aligns seamlessly with our mission to push the boundaries of research and explore the potential benefits of psilocybin for the adolescent brain while simultaneously aiming to minimize any adverse effects." For more information on Rose Hill, visit https://rosehill.life/. About Rose HillRose Hill is a leading innovator in the cultivation and supply of premium psilocybin products and biomass. Dedicated to fostering a sustainable and ethical approach to cultivation, Rose Hill sets industry norms to standards to deliver safe and top-quality products to research partners and brands. Renowned as the foremost psilocybin producer in Jamaica, Rose Hill holds the distinction of being the world's inaugural legal exporter of these transformative compounds. Media Contacts: Francesca DeMauro917.880.9771rosehill@kcsa.com