Monthly Archives: July 2020

Neuroscience

Team Synthesizes Safer Nonaddictive Analgesics – Technology Networks

Researchers at LSU Health New Orleans Neuroscience Center of Excellence and colleagues have discovered a new class of pipeline drugs to relieve pain and reduce fever without the danger of addiction or damage to the liver or kidneys. The research is publishedonlinein theEuropean Journal of Medicinal Chemistry.Current drugs have unwanted side effects. Opioids can not only cause addiction; recent studies have shown they can be no more effective at relieving pain than non-narcotic drugs. Non-steroidal anti-inflammatories (NSAIDs) can cause kidney damage. Acetaminophen is an effective drug, but overuse can result in liver damage.

The research team, led by Drs. Hernan A. Bazan, a professor in the Department of Surgery and Program Director of the Vascular Surgery Fellowship at Ochsner Clinic, and Surjyadipta Bhattacharjee, a post-doctoral researcher at the LSU Health New Orleans Neuroscience Center of Excellence, set out to discover what causes the liver damage associated with acetaminophen and then create a drug structurally similar to acetaminophen -- as effective, but without liver toxicity. Along with the chemistry team led by Professor Julio Alvarez-Builla, Department of Organic Chemistry at the University of Alcala in Madrid, they tested 21 different compounds as acetaminophen analogs.

Senior author Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans Neuroscience Center of Excellence says, The new chemical entities reduced pain in two in models without the liver and kidney toxicity associated with current over-the-counter analgesics that are commonly used to treat pain -- acetaminophen and NSAIDs. They also reduced fever in a pyretic model. This is particularly important in the search for an antipyretic with a safer profile in the COVID-19 pandemic and its associated kidney and liver disease in critically ill SARS-CoV-2 patients.

Acute and chronic pain management is one of the most prevalent and costly public health issues worldwide. According to the Centers for Disease Control and Prevention, an estimated 50 million -- 20.4% of U.S. adults had chronic pain and 8.0% of U.S. adults had high-impact chronic pain in 2016.

Given the widespread use of acetaminophen, the risk of hepatotoxicity with overuse, and the ongoing opioid epidemic, these new chemical entities represent novel, non-narcotic analgesics that exclude hepatotoxicity, for which development may lead to safer treatment of acute and chronic pain and fever, adds Dr. Nicolas Bazan.

Other LSU Health New Orleans members of the research team included William C. Gordon, PhD, Professor of Neuroscience and Ophthalmology; Dennis Paul, PhD, Professor of Pharmacology; Scott Edwards, PhD, Associate Professor of Physiology and Neuroscience; Bokkyoo Jun, PhD, Research Instructor; and Amanda R. Pahng, PhD, a post-doctoral fellow in Dr. Edwards lab. The research team also included Drs. Carolina Burgos, Javier Recio, and Valentina Abet, at the University of Alcala in Madrid; Jessica Heap, a third-year medical student at the Tulane University School of Medicine and Alexander Ledet, a first-year MD/PhD candidate at the Albert Einstein College of Medicine in New York.

The intellectual property behind these new technologies, which are part of this discovery, have been licensed from LSU Health Sciences Center New Orleans to the life science startup South Rampart Pharma, LLC that is currently developing this new drug in late pre-clinical stages. Drs. Hernan A. Bazan, Carolina Burgos, Dennis Paul, Julio Alvarez-Builla, and Nicolas G. Bazan are named inventors on a patent assigned to LSU Health Sciences Center describing the synthesis and characterization of the novel non-hepatotoxic acetaminophen analogs (PCT/US2018/022029). The company expects to file the first FDA IND (Investigational New Drug) application by early third quarter 2020.

Our primary goal is to develop and commercialize new alternative pain medications that lack abuse potential and have fewer associated safety concerns than current treatment options, and this peer-reviewed paper describes the discovery of the initial library of compounds as well as several proof of concept animal and molecular studies, says Dr. Hernan Bazan.

The research was supported by FEDER funds, Comunidad de Madrid, Ministerio de Economia, Industria y Competitividad, Instituto de Salud Carlos III, and Universidad de Alcal.

Reference: Bazan, et al. (2020). A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis. European Journal of Medicinal Chemistry. DOI:https://doi.org/10.1016/j.ejmech.2020.112600

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Neuroscience

How Microglia Chomp Paths Through the Brain’s Scaffolding To Promote Plasticity – Technology Networks

To make new memories, our brain cells first must find one another. Small protrusions that bud out from the ends of neurons' long, branching tentacles dock neurons together so they can talk. These ports of cellular chatter -- called synapses, and found in the trillions throughout the brain -- allow us to represent new knowledge. But scientists are still learning just how these connections form in response to new experiences and information. Now, a study by scientists in UC San Francisco's Weill Institute for Neurosciences has identified a surprising new way that the brain's immune cells help out.

In recent years, scientists have discovered that the brain's dedicated immune cells, called microglia, can help get rid of unnecessary connections between neurons, perhaps by engulfing synapses and breaking them down. But the new study, published July 1, 2020 in Cell, finds microglia can also do the opposite -- making way for new synapses to form by chomping away at the dense web of proteins between cells, clearing a space so neurons can find one another. Continuing to study this new role for microglia might eventually lead to new therapeutic targets in certain memory disorders, the researchers say.

Neurons live within a gelatinous mesh of proteins and other molecules that help to maintain the three-dimensional structure of the brain. This scaffolding, collectively called the extracellular matrix (ECM), has long been an afterthought in neuroscience. For decades, researchers focused on neurons, and, more recently, the cells that support them, have largely considered the ECM unimportant.

But neurobiologists are starting to realize that the ECM, which makes up about 20 percent of the brain, actually plays a role in important processes like learning and memory. At a certain point in brain development, for example, the solidifying ECM seems to put the brakes on the rapid pace at which new neuronal connections turn over in babies, seemingly shifting the brain's priority from the breakneck adaptation to the new world around it, to a more stable maintenance of knowledge over time. Scientists also wonder if a stiffening of the extracellular matrix later in life might somehow correspond to the memory challenges that come with aging.

"The extracellular matrix has been here the whole time," said the study's first author Phi Nguyen, a biomedical sciences graduate student at UCSF. "But it's definitely been understudied."

Nguyen and his advisor, Anna Molofsky, MD, PhD, an associate professor in the UCSF Department of Psychiatry and Behavioral Sciences, first realized the ECM was important to their research on the hippocampus, a brain structure critical for learning and memory, when an experiment yielded unexpected results. Knowing that microglia chew away at obsolete synapses, they expected that disrupting microglia function would cause the number of synapses in the hippocampus to shoot up. Instead, synapse numbers dropped. And where they thought they'd find pieces of synapses being broken down in the "bellies" of microglia, instead they found pieces of the ECM.

"In this case microglia were eating something different than we expected," Molofsky said. "They're eating the space around synapses -- removing obstructions to help new synapses to form."

Before springing into action, the microglia wait for a signal from neurons, an immune molecule called IL-33, indicating that it's time for a new synapse to form, the study found. When researchers used genetic tools to block this signal, microglia failed to fulfill their ECM-chomping duties, leading to fewer new connections between neurons in the brain of mice and leaving mice struggling to remember certain details over time. When researchers instead drove the level of IL-33 signaling up, new synapses increased in number. In older mice, in which brain aging already slows the formation of new connections, ramping up IL-33 helped push the number of new synapses towards a more youthful level.

The study could be important for understanding -- and perhaps one day treating -- the kinds of memory problems we see in age related diseases like Alzheimer's, according to study co-author Mazen Kheirbek, PhD, an associate professor of psychiatry whose lab studies brain circuits involved in mood and emotion. But the findings might also be important for specific types of emotional memory problems sometimes seen in anxiety related disorders.

To determine how changes in IL-33 affect memory, the researchers taught mice to distinguish between an anxiety-inducing box (inside which the mice received a mild foot shock) and a neutral box. After a month, normal mice expressed far more fear in the shock-associated box by freezing in place (a rodent reflex to throw off predators) than they did in the neutral box, where they moved around more casually. But mice with disrupted IL-33 expressed high levels of fear in either box, suggesting they'd lost the kind of precise memory needed to determine when they should be scared and when they were safe.

Kheirbek likens this overgeneralized response to the kind of trauma-induced fear that might result from being mugged in a parking lot at night. Instead of being able to separate that fearful memory from new, perhaps less-threatening experiences, some people might develop a generalized fear that makes it hard for them to enter any parking lot at any time. "Deficits in this ability to have very precise, emotional memories are seen in a lot of anxiety disorders and particularly in PTSD," he said. "It's an overgeneralization of fear that can really interfere with your life."

For Molofsky's part, stumbling upon this unexpected finding has left her eager to learn more about the ECM and how it shapes the way we learn. Her lab is now working to identify new, poorly characterized pieces of the matrix to look for as yet undocumented ways it interacts with neurons and microglia in the brain.

"I'm in love with the extracellular matrix," Molofsky said. "A lot of people don't realize that the brain is made up not just of nerve cells, but also cells that keep the brain healthy, and even the space in between cells is packed with fascinating interactions. I think a lot of new treatments for brain disorders can come from remembering that."

Reference: Nguyen, P. T., Dorman, L. C., Pan, S., Vainchtein, I. D., Han, R. T., Nakao-Inoue, H., Taloma, S. E., Barron, J. J., Molofsky, A. B., Kheirbek, M. A., & Molofsky, A. V. (2020). Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. Cell. https://doi.org/10.1016/j.cell.2020.05.050

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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How Microglia Chomp Paths Through the Brain's Scaffolding To Promote Plasticity - Technology Networks

Neuroscience

AI medical research projects receive $7.1 million funding – News – The University of Sydney

Psychologists, mathematicians and data scientists at the University of Sydney are teaming up to investigate how artificial intelligence (AI) and machine learning technologies can guide effective support and treatment for people with neurological disease and mental health disorders.

The two multidisciplinary projects received more than $7 million federal funding to focus on using AI to develop technology to support youth mental health care and to build an extensive AI network for more accurate diagnosis of neurological disorders such as multiple sclerosis.

Both projects are led by the University of Sydneys Brain and Mind Centre.

The investment into Sydney-led research was announced by the Minister for Health, the Hon Greg Hunt MP as part of the Australian Governments Medical Research Future Fund (MRFF).

Our researchers are at the forefront of addressing crucial gaps in medical research that lead to better health outcomes, said Professor Duncan Ivison, Deputy Vice-Chancellor (Research).

These projects exemplify our commitment to multidisciplinary research and especially harnessing cutting edge research in artificial intelligence with outstanding neuroscience that when combined together will make an enormous contribution to the future of healthcare.

Co-Director and head of Translational Research at the Brain and Mind Centre, Professor Matthew Kiernan, said: The Brain and Mind Centre asks big questions for real-world outcomes. These research programs are based on patient-centred questions, and as such, they draw on collaborations across academic disciplines, health providers and industry partners who bring a unique depth of knowledge to each program.

Professor Michael Barnett, together with the Sydney Neuroimaging Analysis Centre (SNAC) will lead a project awarded $4.02 million to investigate how AI can be paired with medical imaging technologies to set a new standard for the diagnosis, monitoring and treatment of neurological disease.

The Translating AI Networks to Support Clinical Excellence in Neuro Diseases (TRANSCEND) project will build a new, hybrid AI learning ecosystem by training it to recognise biomarkers linked to disease progression of the common, disabling neurological condition, multiple sclerosis.

The project is a collaboration between the University of Sydney, industry specialists in medical imaging and health provider networks.

Professor Barnett, Head of Computational Neuroscience Team at the Brain and Mind Centre, said TRANSCEND fills an important research gap of the future of AI technologies to transform the health sector.

Software-generated artificial neural networks have demonstrated a remarkable capacity for (generic) image recognition. Despite the clear potential for this technology to transform health delivery, particularly through advances in medical imaging, AI research and implementation has remained the purview of research institutes and technology companies with limited access to real-world data.

By incorporating real-world data, TRANSCEND will enable new AI research and technologies within the health sector, while preserving patient privacy and data security.

Dr Frank Iorfino, research fellow in youth mental health and technology at the Brain and Mind Centre and Faculty of Medicine and Health is leading a project using AI to test and quantify the impacts of youth mental health interventions.

Leading the methods and modelling component of the project is statistician ProfessorSally Cripps, director of the University of SydneyCentre for Translational Data Scienceand theARCIndustrial Transformation TrainingCentrefor Data Analytics for Resources and Environments.

The project has been awarded more than $3.1 million.

The study will bring together data and computer scientists, who will work alongside clinicians and health services to develop digital tools that can guide clinical decisions about the appropriate interventions and treatments for young people who seek mental health care.

Mental disorders are the leading cause of disability and death among young people, said Dr Iorfino.

A key challenge for youth mental health care is how to make effective clinical decisions about the timing and sequence of interventions, particularly for those with complex needs. This three-year project will use AI to model youth mental health outcomes and quantify the impact of interventions on these outcomes.

Brain and Mind Centre Co-Director, Youth Mental Health and Policy, Professor Ian Hickie, said: From a clinical perspective, these new approaches could result in real-time decision aids that would help us to make much more accurate decisions about which early interventions are of greatest benefit to young people with emerging major mood or psychotic disorders. They will also guide our efforts to provide the most effective forms of secondary prevention.

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AI medical research projects receive $7.1 million funding - News - The University of Sydney

Neuroscience

Save 98% off this Master the Science of Memory, Leadership & Focus Bundle – Neowin

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Neuroscience

Fine-tuning brain activity reverses memory problems in mice with autism mutation – Spectrum

Social circuitry: Mice with an autism-linked mutation have better social memory after treatment that calms a related neural circuit.

Georgejason / iStock

Dampening overactive brain circuits alleviates social and spatial memory problems in a mouse model of 22q11.2 deletion syndrome, according to a new study1. The findings hint at the possibility of novel treatments for some difficulties associated with the syndrome.

Deletions of DNA in a chromosomal region known as 22q11.2 often cause intellectual disability or other cognitive difficulties, as well as psychiatric conditions such as schizophrenia. About 16 percent of people with the deletion also have autism2.

The type and severity of traits vary from person to person, in part because the deletion can span roughly 20 to 50 genes. That range makes it difficult to design targeted therapies. And many people with deletions in 22q11.2 are prone to drug-related side effects, such as seizures.

Side effects with drug treatment is one of the hardest parts of dealing with mental illness, says Julia Kahn, a postdoctoral researcher at the Childrens Hospital of Philadelphia in Pennsylvania, who worked on the study. Being able to circumvent that in a very directed manner would be really life-changing for a lot of people.

The study identifies the neural circuits responsible for select behaviors in model mice and shows that manipulating those circuits could offer a new treatment strategy.

It suggests that therapies can be symptom specific, says lead investigator Douglas Coulter, professor of pediatrics and neuroscience at the University of Pennsylvania in Philadelphia.

Coulter and his colleagues manipulated circuits in two regions of the hippocampus in 22q11.2 model mice: the ventral region, which governs social memory, and the dorsal region, involved in spatial memory. They focused on the hippocampus because it is important to social cognition in both mice and people, and previous studies have shown it is unusually small in people with 22q11.2 deletions3.

Before the manipulation, mice missing 22q11.2 perform worse than controls on tests of their social and spatial memory, the study shows. The mice do not distinguish between a new mouse and one they have already met, and they have trouble recognizing when an object in their cage has been moved. Brain imaging also showed that the model mice have overactive neurons in the hippocampus.

The team used a method known as chemogenetics to dampen this overactivity. They gave the mice an injection that prompts some neurons in the hippocampus to produce designer receptors. They then injected the animals with an experimental drug that binds only to those receptors, making the neurons less excitable.

The animals behaviors changed, depending on where they received the injection. Social memory improved when the drug targeted the ventral hippocampus, and spatial memory improved when the drug affected neurons in the dorsal area. Too much inhibition in either area caused the animals memory problems to return.

Using the same technique, the researchers also gave control mice drug-sensitive receptors that either activate or quell the same circuits in the hippocampus. After both treatments, the controls showed the same social memory problems as the mice with 22q11.2 deletions. The results indicate that disrupting the circuits in either direction is enough to change behavior, even without any underlying genetic mutations. The findings were published in May in Biological Psychiatry.

Chemogenetics is a long way off from use in people, but drugs currently on the market may be able to achieve similar outcomes by nudging circuits into a more balanced state, says Peter Scambler, professor of molecular medicine at University College London in England, who was not involved in the work.

Its a proof of principle, he says.

Manipulating circuits that govern specific behaviors should be a goal of all current work at this point, says Anthony LaMantia, professor of developmental disorders and genetics at Virginia Polytechnic Institute and State University in Blacksburg, who was not involved in the work. This is much more targeted and precise. It should make everybody in the field think through how to design their experiments.

Targeting circuits in the hippocampus could help people, because findings in the hippocampus in mice typically translate well to humans, says Rebecca Piskorowski, head of the synaptic plasticity and neuronal circuits team at the Institute of Psychiatry and Neuroscience of Paris in France, who was not involved in the work.

This kind of targeting might also help at any age. The method improved memory in adult mice, suggesting similar treatments could help older people with 22q11.2 deletions and not just children.

This paper shows if you just adjust the activity in a tiny little place, you can somehow compensate for all those developmental problems, Piskorowski says. That is particularly exciting.

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Neuroscience

BioXcel Therapeutics Announces Notice of Allowance for US Patent Application Covering Formulation for BXCL501 and Methods of Treating AgitationPatent…

NEW HAVEN, Conn., July 07, 2020 (GLOBE NEWSWIRE) -- BioXcel Therapeutics, Inc. (BTI or Company) (Nasdaq: BTAI), a clinical-stage biopharmaceutical company utilizing artificial intelligence to identify improved therapies in neuroscience and immuno-oncology, today announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for patent application No. 16/453,679 related to BXCL501, the Companys proprietary sublingual thin-film formulation of dexmedetomidine (Dex). The patent is expected to cover film formulations containing Dex and methods of treating agitation using such film formulations.

The allowance of this patent substantially strengthens our intellectual property position, an important milestone for BXCL501s development and potential commercialization, commented Vimal Mehta, Ph.D., Chief Executive Officer of BTI. With a significant need for an effective therapy that addresses the underlying cause of agitation, BXCL501 has the potential to fill this gap, while also providing a unique and favorable delivery method for treating patients. As we prepare to report topline data from our pivotal SERENITY trials this month, we are thrilled to have received this patent allowance for film formulations containing Dex, an essential step in creating value for our shareholders.

A Notice of Allowance is issued after the USPTO makes a determination that a patent should be granted from an application. The patent, which is expected to be issued in the third quarter of 2020, will have a term that expires no earlier than 2039. After issuance, BioXcel plans to list the U.S. patent in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book.

About BXCL501

BXCL501 is a potential first-in-class, proprietary sublingual thin film of dexmedetomidine, a selective alpha-2a receptor agonist for the treatment of acute agitation. BTI believes that BXCL501 directly targets a causal agitation mechanism and the Company has observed anti-agitation effects in clinical studies across multiple neuropsychiatric indications. BXCL501 has also been granted Fast Track Designation by the U.S. Food and Drug Administration for the acute treatment of mild to moderate agitation in schizophrenia, bipolar disorder, and dementia.

A Phase 1b safety and efficacy study of BXCL501 yielded positive dose-response data. BXCL501 is being evaluated in the SERENITY program, consisting of two Phase 3 studies for the acute treatment of agitation in patients with schizophrenia (SERENITY I) and bipolar disorder (SERENITY II). BXCL501 is also being evaluated in the Phase 1b/2 TRANQUILITY trial for the treatment of agitation associated with dementia, as well as the Phase 1b/2 RELEASE trial for the treatment of opioid withdrawal symptoms.

About BioXcel Therapeutics, Inc.

BioXcel Therapeutics, Inc. is a clinical stage biopharmaceutical company focused on drug development that utilizes artificial intelligence to identify improved therapies in neuroscience and immuno-oncology. BTI's drug re-innovation approach leverages existing approved drugs and/or clinically evaluated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indices. BTI's two most advanced clinical development programs are BXCL501, an investigational sublingual thin film formulation in development for acute treatment of agitation resulting from neuropsychiatric disorders, and BXCL701, an investigational orally administered systemic innate immunity activator in development for treatment of a rare form of prostate cancer and for treatment of pancreatic cancer in combination with other immuno-oncology agents. For more information, please visit http://www.bioxceltherapeutics.com.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include but are not limited to receipt of patent approval for BXCL501, the Companys intellectual property strategy, the timing and data from clinical development initiatives and trials for BXCL501, the potential commercialization of BXCL501 and BTIs corporate strategy. When used herein, words including anticipate, being, will, plan, may, continue, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking.

These forward-looking statements are based on managements current expectations and beliefs. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause BTIs actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: its limited operating history; its incurrence of significant losses; its need for substantial additional funding and ability to raise capital when needed; its limited experience in drug discovery and drug development; its dependence on the success and commercialization of BXCL501 and BXCL701 and other product candidates; the failure of preliminary data from its clinical studies to predict final study results; failure of its early clinical studies or preclinical studies to predict future clinical studies; its ability to receive regulatory approval for its product candidates; its ability to enroll patients in its clinical trials; undesirable side effects caused by BTIs product candidates; its approach to the discovery and development of product candidates based on EvolverAI is novel and unproven; its exposure to patent infringement lawsuits; its ability to comply with the extensive regulations applicable to it; impacts from the COVID-19 pandemic; its ability to commercialize its product candidates; and the other important factors discussed under the caption Risk Factors in its Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2020, as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SECs website at http://www.sec.gov and Investors sections of our website at http://www.bioxceltherapeutics.com.

These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While BTI may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing BTIs views as of any date subsequent to the date of this press release.

Contact Information:BioXcel Therapeutics, Inc.www.bioxceltherapeutics.com

Investor Relations:John Grazianojgraziano@troutgroup.com1.646.378.2942

Media:Julia Deutschjdeutsch@troutgroup.com1.646.378.2967

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BioXcel Therapeutics Announces Notice of Allowance for US Patent Application Covering Formulation for BXCL501 and Methods of Treating AgitationPatent...

Neuroscience

University of Miami Miller School Plays Pivotal Role in Securing a $15 Million National Alzheimers Disease Research Center – Newswise

Newswise University of Miami Miller School of Medicine investigators play a pivotal role in a consortium of Florida institutions just awarded a $15 million grant to collaborate on Alzheimers disease research.

The five-year National Institutes of Health/National Institute on Aging grant brings together top Florida researchers to focus on better understanding how to diagnose, treat, prevent, and potentially cure Alzheimers in diverse populations.

The 1Florida Alzheimers Disease Research Center, or1Florida ADRC, will be recruiting participants from the University of Miami Miller School of Medicine, the University of Florida, and Mount Sinai Medical Center in Miami Beach. Investigators from these institutions will also be collaborating other Florida academic institutions including Florida Atlantic University and Florida International University.

We are honored that this Alzheimers Disease Research Center is one of 31 centers of excellence designated by the National Institute on Aging. Of the 31 centers in the U.S., the 1Florida ADRC is the only funded center in Florida, said David Loewenstein, Ph.D., ABPP/CN, associate director of 1Florida ADRC and director of the Center for Cognitive Neuroscience and Aging (CNSA) at the Miller School.

Miller School researchers are involved in all aspects of the 1Florida ADRC, including recruitment, onsite evaluation, and research. Dr. Loewenstein is leading the Miller School investigative team. Other UM researchers include Rosie E. Curiel Cid, Psy.D., leader of the1Florida ADRC Outreach, Recruitment and Engagement Core, associate professor and chief, cross-cultural neuropsychology and cognitive neuroscience, in the Center for Cognitive Neuroscience and Aging; Elizabeth Crocco, M.D., chief of geriatric psychiatry and director of UMs state-funded Memory Disorders Clinic and medical director of the CNSA, who will be running the medical aspects of the 1Florida ADRC; and Tatjana Rundek, M.D., Ph.D., professor of neurology and Evelyn F. McKnight Endowed Chair for Learning and Memory in Aging, who is co-leading the ADRCs educational core with Glenn Smith, Ph.D., ABPP/CN, from the University of Florida.

The Miller School is recruiting hundreds of older adults from our local community, said Dr. Loewenstein. Their focus is on engaging African American and Hispanic older adults to make sure they are well represented, because these groups are historically largely under-represented in aging research, including studies looking at Alzheimers disease.

I am the daughter of Cuban exiles; the first to be born in this country. Spanish was my first language. Miami has nurtured this multicultural identity and I am privileged to bring it to the forefront of my work, Dr. Curiel said. One of the greatest challenges in aging research is ensuring that the methods we develop to detect and treat diseases of the aging brain are generalizable toallolder adults. The CNSA is committed to addressing this by developing tools and methods that are cross-culturally applicable. Now, the 1Florida ADRC will significantly broaden our reach. We assembled a passionate team of scientists from diverse cultural backgrounds to engage, educate, listen to, and partner with our richly diverse communities. We hope to generate new knowledge and contribute to national efforts to accelerate clinically meaningful outcomes for older adults and their families.

To better understand diseases of the aging brain, even decades before they occur, the ADRC scientists have an expertise in studying people who dont yet have symptoms but might be concerned about their risk for developing Alzheimers for another reason, such as family history. They also study older adults who may have thinking or memory problems but havent yet been diagnosed, as well as people who have been diagnosed with early mild cognitive impairment.

People in the study will receive annual evaluations including comprehensive neuropsychological testing, a careful clinical examination, an MRI scan of the brain and an amyloid scan, Dr. Loewenstein said. We will follow them on an annual basis.

Dr. Loewenstein and colleagues at the Miller School developed a novel cognitive stress test, called the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) test, which will be used in the 1Florida ADRC study. LASSI-L is a scientifically proven measure that is highly sensitive to early Alzheimers disease brain pathology and can pick up early changes in memory before traditional cognitive testing detects the disease.

The Miller School also stands out for being the only university in the state funded by the NIH to conduct tau imaging. Miller School researchers have a number of federally funded grants that are studying abnormal tau protein in the brain. The presence of amyloid alone is not the only indication of future Alzheimers disease. Some people start to show signs of tau deposition years, even decades, before developing symptoms.

The University of Miami Miller School of Medicine brings something very special to the table and that is why we were asked to be a major part of this initiative. It was because of our strengths in novel cognitive testing, neuroimaging and ability to engage and recruit persons from diverse cultures, Dr. Loewenstein said.

The 1Florida ADRC will also help to train the next generation of scientists in Alzheimers and other neurodegenerative diseases. Dr. Rundek said the ADRCs Research Education Component, called 1Florida Alzheimer's Disease Science Training to Advance Research Success, or AlzSTARS, will train diverse, multidisciplinary early stage investigators at all participating institutions for leadership roles in research translation, especially in regard to diverse and underserved communities.

The AlzSTARS program will provide a unique opportunity for our young trainees from diverse backgrounds to train with clinical and research leaders in Alzheimers disease across Florida and the nation. They will become the next generation of leaders and scientists to successfully translate scientific discoveries to prevention and treatment of Alzheimers disease, Dr. Rundek said.

Dr. Crocco, who has devoted more than 22 years to working with South Floridas older population affected by Alzheimers disease, will also offer her expertise in Alzheimers disease and related disorders to the 1Florida ADRC Clinical Core.

The ADRC brings us to the level of a national center of excellence, Dr. Crocco said. We have the funding and the ability now to be able to promote and really develop more and more these wonderful diagnostic strategies, treatment strategies and, hopefully, one day a cure for Alzheimers disease and other neurodegenerative disorders.

Florida is home to about 12% of the approximately 5.4 million people in the U.S. who have Alzheimers disease. For more information about 1Florida ADRC including how to participate, visitwww.1floridaadrc.org, emailinfo@1floridaadrc.orgor call 352-273-7425 or 305-355-9080.

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University of Miami Miller School Plays Pivotal Role in Securing a $15 Million National Alzheimers Disease Research Center - Newswise

Embryology

Infertile couples overestimate their chance of IVF success – BioNews

7 July 2020

Couples undergoing fertility treatment markedly overestimate their chance of IVF success, men to a greater extentthan women, according to new research.

The research presented at the virtual meeting of the European Society of Human Reproduction and Embryology 2020 came from a small, single-centre study at Leuven University fertility clinic in Belgium.

'Clinics do share average success rates on their websites, but these are often only relevant to a reference population of younger patients. And many patients do not think that average success rates apply to them. They expect greater success, thinking of their healthy lifestyle or their experienced doctors,' said study author embryologist Johanna Devroe.

Sixty-nine couples who were about to start at second or subsequent IVF cycles separately completed a questionnaire assessing their dispositional outlook and estimated their chances of IVF success. The data was then compared with the couples' personalised calculated chance of IVF live birth.

The mean calculation of live birth rate for participants in the study was 32 percent, however, the vast majority of both women and men greatly overestimated their chances of success. Women overestimated by a factor of 1.8, while men overestimated their chance of success by a factor of 2.3 with over halfof the men expecting their birth rate to be more than double their calculated prognosis.

'Partners didn't differ in their dispositional outlook so we cannot fully explain the higher expected live birth rate in men by a difference in optimism,' said Devroe. 'We are now investigating this, to see if disclosing an individual's predicted success rate rather than a clinic's average success rate helps to set realistic expectations.'

Sarah Norcross, director of fertility and genetics charity, the Progress Educational Trust, said: 'This interesting, though not surprising, single-centre study, shows just how much both men and women hoping to become parents overestimate their chances of success following fertility treatment. It sends an important message to fertility clinics about the need to manage patients' expectations and support them before, during and after fertility treatment. The dramatic mismatch shown by this study where the vast majority of both men and women estimated their chance of success to be double what it actually was shows just how shocking it can be for couples when IVF does not work which is, sadly, what happens two-thirds of the time.'

Dr Raj Mathur, consultant gynaecologist and fertility lead at St Mary's hospital, Manchester, told BioNews: 'The findings will resonate with members of the British Fertility Society, who aim to counsel patients properly about their individual chances, while at the same time recognising the innate human bias towards positivity and hope. We support clinics and the UK fertility regulator, the Human Fertilisation and Embryology Authority in displaying success rates in a uniform way that can be understood by patients, and we feel that the relationship between patients and their clinicians is of the utmost importance in making decisions about whether to start or continue complex fertility treatment.'

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Infertile couples overestimate their chance of IVF success - BioNews

Embryology

New practical recommendations for the use of time-lapse technology in ART – ESHRE

New recommendations from ESHRE concentrate on the practicalities of introducing a time-lapse system into IVF labs, not on its use solely to improve delivery rates.

Despite such hopes and its widespread uptake, a lack of good practice guidelines for TLT in IVF has persisted. Now, the wait is over. Debbie Montjean, a member of the ESHREs SIG Embryology and one of 11 international contributors, presented details of the long awaited recommendations for TLT at this years virtual annual meeting. The collaborative effort has now produced a set of good-practice recommendations for the introduction and application of TLT, a comprehensive literature review and detailed time points for annotating development, whilst finely balancing both the pros and cons of this technology.(1)

The published recommendations, as Montjean emphasised, are not set out as a blueprint for improving embryo selection or delivery rates, but provide extensive support to IVF laboratories embarking on investment in TLT and standardisation and structure to those with the systems already in place. In addition, the publication emphasises the need for consistent nomenclature and annotations of morphokinetics, guidelines which were previously published but further summarised within this publication.(2)

For newcomers to the technology the recommendations are divided into a user-friendly 11-step guide to the best approach to introduction and application. The publication comprehensively reviews all versions of TLT currently available, comparing an extensive range of user requirement specifications in hardware, software and the on-going costs of technical support and maintenance.

Acknowledging the initial excitement when TLT was first introduced, with obvious implications for the efficiency of ART treatment, the authors propose that these expectations are yet to be met; indeed, the integration of TLT within the ART laboratory has not yet increased IVF success rates as once hoped. Yet, added Montjean, clinical outcomes arent the only advantage to justify use. Significant importance to other laboratory activities should not be ignored, she said. Undisturbed and stable culture conditions combined with improvements in laboratory workflow, flexibility and efficiency are substantial benefits. Moreover, TLT has undoubtedly revealed further biological markers and development anomalies which are otherwise undetected in traditional culture and static embryo assessments. Thus, the recommendations summarise 20 atypical features in human embryo cleavage development, 13 of which are exclusively observed using TLT and the remaining seven better observed when assisted by TLT. Such observations of subtle embryo anomalies and early mitosis can assist in blastocyst prediction with higher sensitivity and accuracy. Montjean ended her online presentation noting that time-lapse will at least help you to prioritise embryos and ultimately shorten your time to pregnancy.

Until now the absence of good practice guidelines for TLT and a lack of standardisation might be a reason for the inconsistent results among global users of the technology. But the authors here recognise that TLT is here to stay in the IVF lab; perhaps a standardisation of practice may unify the data and point towards an improvement in IVF success rates.

1. ESHRE Working group on Time-Lapse technology. Good practice recommendations for the use of time-Lapse technology. Hum Reprod Open 2020; doi: 10.1093/hropen/hoaa008.2. Ciray HN, Campbell A, Agerholm AE, et al. Proposed guidelines on the nomenclature and annotation of dynamic human embryo monitoring by a time lapse user group. Human Reprod 2014; 29: 2650-2660.

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New practical recommendations for the use of time-lapse technology in ART - ESHRE

Embryology

Risk of IVF babies being born with cerebral palsy halves due to decline in twins, study reveals – The Telegraph

The risk of IVF babies being born with cerebral palsy has fallen by 50 per cent due to the decline in twins, a study has found.

Fewer twins are being conceived using the method because doctors are reducing the practice of implanting multiple embryos into the woman's womb, according to scientists at Copenhagen University Hospital in Denmark.

Women who have just one embryo transferred during IVF treatment are five times more likely to give birth to a healthy baby as there is less risk the child will be born low-weight or delivered prematurely, researchers from the University of Aberdeen previously found.

IVF twin rates have declined from almost 25 per cent in the 1990s to less than 5 per cent today.

This latest study now indicates that the number of babies being born with cerebral palsy, a condition which affects movement and coordination, has more than halved in the past 20 years and the risk is now equal to those conceived naturally.

Using data from Denmark, Finland and Sweden, the researchers examined some 112,000 IVF children born over 24 years.

They found that the prevalence of cerebral palsy among single babies born from IVF decreased from 8.5 per 1,000 to the normal population rate of 2.8. For twins, the rate remained stable at 10.9.

Dr Anne Lrke Spangmose presented the findings at the online Annual Meeting of the European Society of Human Reproduction and Embryology.

"The inclusion of complete IVF and naturally conceived birth cohorts makes our data robust and has allowed assessment of the true risk of cerebral palsy in IVF and its decline over time," she said.

"Multiple embryo transfer is still standard care in many countries. Our findings emphasise that single embryo transfer and singleton births should be encouraged worldwide."

Large registry studies have shown that the risk of cerebral palsy has virtually disappeared in IVF children born in the Nordic countries after a policy of single embryo transfer was introduced in the early 2000s.

The NHS recommends that women aged 39 and under should have a single embryo transfer where possible, while women aged 40 and above can have a double embryo transfer.

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Risk of IVF babies being born with cerebral palsy halves due to decline in twins, study reveals - The Telegraph