Neuroscience

Global Genomic Diversity: Unveiling the New Pangenome Reference – Neuroscience News

Summary: The Human Pangenome Reference Consortium has released a comprehensive collection of human genome sequences that captures remarkable diversity across global populations.

The new pangenome reference includes 94 distinct genome sequences from 47 individuals, with plans to increase this to 700 sequences from 350 people by mid-2024.

This expanded reference will better represent the genetic diversity of the human species and help reduce health disparities in genomic analyses. It also introduces over 100 million new DNA bases, and can more accurately identify larger genomic variants.

Key Facts:

Source: NIH

Researchers have released a new high-quality collection of reference human genome sequences that captures substantially more diversity from different human populations than what was previously available.

The work was led by the international Human Pangenome Reference Consortium, a group funded by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health.

The new pangenome reference includes genome sequences of 47 people, with the researchers pursuing the goal of increasing that number to 350 by mid-2024. With each person carrying a paired set of chromosomes, the current reference actually includes 94 distinct genome sequences, with a goal of reaching 700 distinct genome sequences by the completion of the project.

The work, appearing in the journalNature, is one of several papers published today by consortium members.

A genome is the set of DNA instructions that helps each living creature develop and function. Genome sequences differ slightly among individuals. In the case of humans, any two peoples genomes are, on average, more than 99% identical.

The small differences contribute to each persons uniqueness and can provide insights about their health, helping to diagnose disease, predict outcomes and guide medical treatments.

To understand these genomic differences, scientists create reference human genome sequences for use as a standard a digital amalgamation of human genome sequences that can be used as a comparison to align, assemble and study other human genome sequences.

The original reference human genome sequence is nearly 20 years old and has been regularly updated as technology advances and researchers fix errors and discover more regions of the human genome.

However, it is fundamentally limited in its representation of the diversity of the human species, as it consists of genomes from only about 20 people, and most of the reference sequence is from only one person.

Everyone has a unique genome, so using a single reference genome sequence for every person can lead to inequities in genomic analyses, said Adam Phillippy, Ph.D., senior investigator in the Computational and Statistical Genomics Branch within NHGRIs Intramural Research Program and a co-author of the main study.

For example, predicting a genetic disease might not work as well for someone whose genome is more different from the reference genome.

The current reference human genome sequence has gaps that reflect missing information, especially in areas that were repetitive and hard to read.

Recent technological advances such as long-read DNA sequencing, which reads longer stretches of the DNA at a time, helped researchers fill in those gaps to create thefirst complete human genome sequence.

This complete human genome sequence, released last year as part of the NIH-funded Telomere-to-Telomere (T2T) consortium, is incorporated into the current pangenome reference. In fact, many of the T2T researchers are also members of the Human Pangenome Reference Consortium.

Using advanced computational techniques to align the various genome sequences, the researchers constructed a new human pangenome reference with each assembly in the pangenome covering more than 99% of the expected sequence with more than 99% accuracy. It also builds upon the previous reference genome sequence, adding over 100 million new bases, or letters in DNA.

While the previous reference genome sequence was single and linear, the new pangenome represents many different versions of the human genome sequence at the same time. This gives researchers a wider range of options for using the pangenome in analyzing other human genome sequences.

By using the pangenome reference, we can more accurately identify larger genomic variants called structural variants, said Mobin Asri, a Ph.D. student at the University of California Santa Cruz and co-first author of the paper.

We are able to find variants that were not identified using previous methods that depend on linear reference sequences.

Structural variants can involve thousands of bases. Until now, researchers have been unable to identify the majority of structural variants that exist in each human genome using short-read sequencing due to the bias of using a single reference sequence.

The human pangenome reference will enable us to represent tens of thousands of novel genomic variants in regions of the genome that were previously inaccessible, said Wen-Wei Liao, a Ph.D. student at Yale University and co-first author of the paper.

With a pangenome reference, we can accelerate clinical research by improving our understanding of the link between genes and disease traits.

The total cost of supporting the work of the Human Pangenome Reference Consortium is projected to be about $40 million over five years, which includes efforts to create the human pangenome reference, improve DNA sequencing technology, operate a coordinating center, conduct outreach and create resources for the research community to use the pangenome reference.

Many of the individuals whose genomes were sequenced for constructing the new human pangenome reference were originally recruited as part of the1,000Genomes Project, a collaborative and international effort funded in part by NIH that aimed to improve the catalog of genomic variants in diverse populations.

Because the human pangenome reference is a work in progress, researchers from the international Human Pangenome Reference Consortium continue to add more genome sequences to increasingly improve the quality of the pangenome reference.

Basic researchers and clinicians who use genomics need access to a reference sequence that reflects the remarkable diversity of the human population. This will help make the reference useful for all people, thereby helping to reduce the chances of propagating health disparities, said Eric Green, M.D., Ph.D., NHGRI director.

Creating and enhancing a human pangenome reference aligns with NHGRIs goal of striving for global diversity in all aspects of genomics research, which is crucial to advance genomic knowledge and implement genomic medicine in an equitable way.

In line with this effort, the Human Pangenome Reference Consortium includes an embedded ethics group that is working to anticipate challenging issues and help guide informed consent, prioritize the study of different samples, explore possible regulatory issues pertaining to clinical adoption, and work with international and Indigenous communities to incorporate their genome sequences in these broader efforts.

Institutions involved in theHuman Pangenome Reference Consortium may be found on the projects main page.

Author: Sarah BatesSource: NIHContact: Sarah Bates NIHImage: The image is credited to Neuroscience News

Original Research: Open access.A draft human pangenome reference by Wen-Wei Liao et al. Nature

Abstract

A draft human pangenome reference

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals.

These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels.

Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci.

We also add 119million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90million of the additional base pairs are derived from structural variation.

Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detectedper haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

See original here:
Global Genomic Diversity: Unveiling the New Pangenome Reference - Neuroscience News

Neuroscience

Shared Genetic Defects in ALS and FTD: New Insights Into … – Neuroscience News

Summary: Some patients with ALS/motor neuron disease (MND) and frontotemporal dementia (FTD) carry the same rare genetic defects that cause other neurodegenerative diseases. These defects, known as short tandem repeat expansions, are the cause of more than 20 neurodegenerative diseases including spinocerebellar ataxias and myotonic dystrophy.

The study suggests a shared risk factor and mechanism that cause nerves to die in different neurodegenerative diseases, which may lead to shared therapeutic strategies in the future.

Key Facts:

Source: Macquarie University

New research has discovered that some patients with ALS/motor neuron disease (MND) and frontotemporal dementia (FTD) carry the same rare genetic defects that cause other neurodegenerative diseases.

Researchers from the Macquarie University MND Research Centre and The Walter and Eliza Hall Institute of Medical Research have identified the defects in the genomes of some people with non-inherited, or sporadic, ALS and FTD.

ALS/MND results in the death of the neurons, or motor nerves, connecting the brain and spinal cord to the muscles. These are the cells that control our ability to move, breathe and swallow. The disease is progressive and eventually fatal.

FTD also causes the death of neurons in part of the brain, resulting in a range of progressive symptoms such as memory loss, unusual behavior, personality changes and communication problems. It is the same form of dementia with which actor Bruce Willis was recently diagnosed, and unlike older-onset dementia, it tends to affect people under 65.

The majority of cases in both diseases about 90 percent in the case of MND and 60-70 percent in FTD are sporadic, with the rest occurring in families.

These gene defects, known as short tandem repeat expansions, are the cause of more than 20 neurodegenerative diseases including spinocerebellar ataxias and myotonic dystrophy. This Australian study has been the most comprehensive assessment of these gene defects in ALS and FTD patients worldwide.

Macquarie University Postdoctoral Research Fellow Dr Lyndal Henden says the findings were a surprise.

We found almost 18 percent of sporadic ALS and FTD patients carried a DNA repeat expansion thought to be involved in other degenerative diseases, she says.

Finding this genetic connection between ALS and FTD offers a fresh opportunity to uncover common risk factors for neuron death, and it will have implications for understanding both diseases.

Macquarie University Associate Professor Kelly Williams directed the study, and says the team suspected there could be some overlap with other diseases, but not to such an extent.

This suggests shared risk factors among these diseases, shared mechanisms that cause nerves to die and perhaps shared therapeutic strategies in the future, she says.

While the causes of sporadic ALS and FTD remain unknown, this is an important step in a long-term effort to identify the risk factors for developing one of these diseases.

Work can now begin to understand how these shared repeat expansions contribute to neuron death.

Thestudy, published in the latest edition of the journalScience Advances, is the culmination of 10 years of research that could not have been possible without the cooperation of patients with ALS and FTD, who have donated biological samples for DNA at both Macquarie University and the University of Sydney.

Author: Georgia GowingSource: Macquarie UniversityContact: Georgia Gowing Macquarie UniversityImage: The image is credited to Neuroscience News

Original Research: Open access.Short tandem repeat expansions in sporadic amyotrophic lateral sclerosis and frontotemporal dementia by Lyndal Henden et al. Science Advances

Abstract

Short tandem repeat expansions in sporadic amyotrophic lateral sclerosis and frontotemporal dementia

Pathogenic short tandem repeat (STR) expansions cause over 20 neurodegenerative diseases. To determine the contribution of STRs in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), we used ExpansionHunter, REviewer, and polymerase chain reaction validation to assess 21 neurodegenerative disease-associated STRs in whole-genome sequencing data from 608 patients with sporadic ALS, 68 patients with sporadic FTD, and 4703 matched controls.

We also propose a data-derived outlier detection method for defining allele thresholds in rare STRs. ExcludingC9orf72repeat expansions, 17.6% of clinically diagnosed ALS and FTD cases had at least one expanded STR allele reported to be pathogenic or intermediate for another neurodegenerative disease.

We identified and validated 162 disease-relevant STR expansions inC9orf72(ALS/FTD),ATXN1[spinal cerebellar ataxia type 1 (SCA1)],ATXN2(SCA2),ATXN8(SCA8),TBP(SCA17),HTT(Huntingtons disease),DMPK[myotonic dystrophy type 1 (DM1)],CNBP(DM2), andFMR1(fragile-X disorders).

Our findings suggest clinical and pathological pleiotropy of neurodegenerative disease genes and highlight their importance in ALS and FTD.

Read the rest here:
Shared Genetic Defects in ALS and FTD: New Insights Into ... - Neuroscience News

Neuroscience

Cannabis Use Disorder Linked to Increased Schizophrenia Risk in … – Neuroscience News

Summary: Young men who suffer from cannabis use disorder are more likely to develop schizophrenia, according to a new study.

The study analyzed health records data of over 6 million people in Denmark and discovered a strong association between cannabis use disorder and schizophrenia. 30% of cases of schizophrenia among men aged 21-30 may be prevented by treating cannabis use disorder.

Effective treatments for both conditions are available, making it imperative to expand prevention, screening, and treatment for people who experience mental illnesses associated with cannabis use.

Key Facts:

Source: NIH

Young men with cannabis (marijuana) use disorder have an increased risk of developing schizophrenia, according to a study led by researchers at the Mental Health Services in the Capital Region of Denmark and the National Institute on Drug Abuse (NIDA) at the National Institutes of Health.

The study, published inPsychological Medicine(link is external),analyzed detailed health records data spanning 5 decades and representing more than 6 million people in Denmark to estimate the fraction of schizophrenia cases that could be attributed to cannabis use disorder on the population level.

Researchers found strong evidence of an association between cannabis use disorder and schizophrenia among men and women, though the association was much stronger among young men. Using statistical models, the study authors estimated that as many as 30% of cases of schizophrenia among men aged 21-30 might have been prevented by averting cannabis use disorder.

Cannabis use disorderandschizophreniaare serious, but treatable, mental disorders that can profoundly impact peoples lives. People with cannabis use disorder areunable to stop using cannabis despite it causing negative consequences in their lives. Schizophrenia is a serious mental illness that affects how a person thinks, feels, and behaves.

People with schizophrenia may seem like they have lost touch with reality, and the symptoms of schizophrenia can make it difficult to participate in usual, everyday activities. However, effective treatments are available for both cannabis use disorder and schizophrenia.

The entanglement of substance use disorders and mental illnesses is a major public health issue, requiring urgent action and support for people who need it, said NIDA Director and study coauthor Nora Volkow, M.D.

As access to potent cannabis products continues to expand, it is crucial that we also expand prevention, screening, and treatment for people who may experience mental illnesses associated with cannabis use.

The findings from this study are one step in that direction and can help inform decisions that health care providers may make in caring for patients, as well as decisions that individuals may make about their own cannabis use.

Previous studies indicate that rates of daily or near daily cannabis use, cannabis use disorder, and new schizophrenia diagnoses are higher among men than women, and that early, frequent cannabis use is associated with an increased risk of developing schizophrenia.

However, few studies have examined differences in the relationship between cannabis use disorder and schizophrenia across different sex and age groups at the population level.

To address this research gap, investigators analyzed data from nationwide health registers in Denmark, which included health records data from more than 6.9 million people who were aged 16-49 at some point between 1972 and 2021.

Using these nationally representative longitudinal data, the researchers investigated how the associations between cannabis use disorder and schizophrenia varied by different sex and age groups, and how these differences changed over time.

Although there are many risk factors associated with schizophrenia, in this study, researchers sought to estimate the proportion of all schizophrenia cases that may be attributed to cannabis use disorder specifically, across sex and age groups at the population level.

The study team estimated that 15% of cases of schizophrenia among men aged 16-49 may have been avoided in 2021 by preventing cannabis use disorder, in contrast to 4% among women aged 16-49.

For young men aged 21-30, they estimated that the proportion of preventable cases of schizophrenia related to cannabis use disorder may be as high as 30%.

The authors emphasize that cannabis use disorder appears to be a major modifiable risk factor for schizophrenia at the population level, particularly among young men.

This study also adds toexisting evidencesuggesting that the proportion of new schizophrenia cases that may be attributed to cannabis use disorder has consistently increased over the past five decades.

The authors note that this increase is likely linked to the higher potency of cannabis and increasing prevalence of diagnosed cannabis use disorder over time.

Increases in the legalization of cannabis over the past few decades have made it one of the most frequently used psychoactive substances in the world, while also decreasing the publics perception of its harm.

This study adds to our growing understanding that cannabis use is not harmless, and that risks are not fixed at one point in time, said Carsten Hjorthj, Ph.D., lead author of the study and associate professor at the Mental Health Services in the Capital Region of Denmark and at the University of Copenhagen.

The authors note that further research is needed to examine potential differences in the potency and frequency of cannabis consumption between young men and women, and to examine the mechanisms underlying the higher vulnerability of young men to the effects of cannabis on schizophrenia.

The association of cannabis potency with cannabis use disorder andpsychosismay help inform public health guidelines; policies on cannabis sales and access; and efforts to effectively prevent, screen for, and treat cannabis use disorder and schizophrenia.

Author: NIDA Press OfficeSource: NIHContact: NIDA Press Office NIHImage: The image is credited to Neuroscience News

Original Research: Open access.Association between cannabis use disorder and schizophrenia stronger in young males than in females by Nora Volkow et al. Psychological Medicine

Abstract

Association between cannabis use disorder and schizophrenia stronger in young males than in females

Background

Previous research suggests an increase in schizophrenia population attributable risk fraction (PARF) for cannabis use disorder (CUD). However, sex and age variations in CUD and schizophrenia suggest the importance of examining differences in PARFs in sex and age subgroups.

Methods

We conducted a nationwide Danish register-based cohort study including all individuals aged 1649 at some point during 19722021. CUD and schizophrenia status was obtained from the registers. Hazard ratios (HR), incidence risk ratios (IRR), and PARFs were estimated. Joinpoint analyses were applied to sex-specific PARFs.

Results

We examined 6 907 859 individuals with 45 327 cases of incident schizophrenia during follow-up across 129 521 260 person-years. The overall adjusted HR (aHR) for CUD on schizophrenia was slightly higher among males (aHR = 2.42, 95% CI 2.332.52) than females (aHR = 2.02, 95% CI 1.892.17); however, among 1620-year-olds, the adjusted IRR (aIRR) for males was more than twice that for females (males: aIRR = 3.84, 95% CI 3.434.29; females: aIRR = 1.81, 95% CI 1.532.15). During 19722021, the annual average percentage change in PARFs for CUD in schizophrenia incidence was 4.8 among males (95% CI 4.35.3;p< 0.0001) and 3.2 among females (95% CI 2.53.8;p< 0.0001). In 2021, among males, PARF was 15%; among females, it was around 4%.

Conclusions

Young males might be particularly susceptible to the effects of cannabis on schizophrenia. At a population level, assuming causality, one-fifth of cases of schizophrenia among young males might be prevented by averting CUD. Results highlight the importance of early detection and treatment of CUD and policy decisions regarding cannabis use and access, particularly for 1625-year-olds.

Link:
Cannabis Use Disorder Linked to Increased Schizophrenia Risk in ... - Neuroscience News

Neuroscience

Depression Symptoms in Older People on the Decline – Neuroscience News

Summary: A recent study reveals that todays 75- and 80-year-olds experience fewer depressive symptoms and greater life satisfaction than their counterparts from the 1990s. The improvement in mental well-being is attributed to better-perceived health and higher education among the aging population. The research further supports the notion that older individuals today have better physical and cognitive functioning than those born earlier.

Key Facts:

Source: University of Jyvskyl

Depressive symptoms have decreased among older people and they are more satisfied with their lives so far than people at the same age three decades ago.

This was observed in a study conducted at the Gerontology Research Center at the Faculty of Sport and Health Sciences, University of Jyvskyl (Finland).

The study examined differences in depressive symptoms and life satisfaction between current 75- and 80-year-olds and same-aged people who lived in the 1990s.

The results showed that 75- and 80-year-old men and women today experience fewer depressive symptoms than those who were 75 and 80 years old in the 1990s. The differences were partly explained by the better-perceived health and higher education of those born later.

In our previous comparisons, we found that older people today have significantly better physical and cognitive functioning at the same age compared to those born earlier, says ProfessorTaina Rantanenfrom the Faculty of Sport and Health Sciences.

These new results complement these positive findings in terms of mental well-being.

Today, 75- and 80-year-olds are more satisfied with their lives to date. However, 80-year-old men who lived in the 1990s were even more satisfied with their current lives than 80-year-old men today.

These men born in 1910 had lived through difficult times, which may explain their satisfaction with their current lives in the 1990s when many things were better than before, says postdoctoral researcherTiia Keklinen.

Individuals adapt to their situation and living conditions. Both in the 1990s and today, the majority of older adults reported being satisfied with their current lives.

The study was conducted at the Faculty of Sport and Health Sciences and Gerontology Research Center at University of Jyvskyl, Finland.

The first cohort consisted of 617 individuals born in 1910 and 1914 who participated in the Evergreen study in 19891990. The second cohort consisted of 794 individuals born in 19381939 and 19421943 who participated in the AGNES study in 20172018. In both cohorts, the participants were assessed at the age of 75 or 80 years.

Funding: The study was funded by the Academy of Finland and the European Research Council.

Author: Tiia KeklinenSource: University of JyvskylContact: Tiia Keklinen University of JyvskylImage: The image is credited to Neuroscience News

Original Research: Open access.Cohort Differences in Depressive Symptoms and Life Satisfaction in 75- and 80-Year-Olds: A Comparison of Two Cohorts 28 Years Apart by Keklinen, T et al. Journal of Aging and Health

Abstract

Cohort Differences in Depressive Symptoms and Life Satisfaction in 75- and 80-Year-Olds: A Comparison of Two Cohorts 28 Years Apart

To examine birth cohort differences in depressive symptoms and life satisfaction in older men and women and the mechanisms underpinning the possible cohort differences.

Two independent cohorts of Finnish men and women aged 75 and 80 were assessed in 19891990 (n= 617) and 20172018 (n= 794). They reported their depressive symptoms (CES-D), current life satisfaction, and evaluation of life until now.

The later-born cohort reported fewer depressive symptoms (8.6 7.1 vs. 13.9 8.3) and the differences were similar for the subdomains of depressive symptoms. The later-born cohort was more often mostly satisfied with life until now (90 vs. 70%) but not with the current life than the earlier-born cohort. Better self-rated health and education of the later-born cohort partly explain the cohort differences.

Older people in Finland report fewer depressive symptoms and they are more satisfied with their past life compared to their counterparts assessed 28years ago.

Go here to read the rest:
Depression Symptoms in Older People on the Decline - Neuroscience News

Neuroscience

Menthol Inhalation May Boost Cognitive Ability in Alzheimer’s – Neuroscience News

Summary: Menthol inhalation can improve cognitive abilities in animal models of Alzheimers disease, researchers report.

Short, repeated exposure to menthol can modulate the immune system and prevent cognitive decline commonly seen in Alzheimers.

Researchers found that the smell of menthol reduced the level of interleukin-1-beta (IL-1b), a protein crucial to the inflammatory response. By inhibiting this protein with a specific drug, cognitive abilities were also improved in the mice models.

This research suggests the possibility of therapies based on stimulating the olfactory system to counteract Alzheimers and other central nervous system diseases.

Key Facts:

Source: Universidad de Navarra

Researchers fromCima University of Navarra(Spain) have shown in animal models ofAlzheimers diseasethat inhaling menthol improves cognitive ability.

This study discovered that repeated short exposures to this substance can modulate the immune system and prevent the cognitive deterioration typical of this neurodegenerative disease.

When analyzing its mechanism of action, they observed that when smelling this aroma, the level ofinterleukin-1-beta (IL-1b), a critical protein mediating the inflammatory response, was reduced.

Furthermore, by inhibiting this protein with a drug approved for the treatment of some autoimmune diseases, they were also able to improve cognitive ability in these diseased mice.

This research highlights the potential of odors and immune modulators as therapeutic agents. Furthermore, it opens the door to developing therapies based on stimulating and training the olfactory system to prevent or alleviate the effects of Alzheimers and other diseases of the central nervous system.

Frontiers in Immunologypublished the results of this study in its latest issue.

The functional balance of the brain depends on complex interactions between various types of nerve cells, immune cells, and neural stem cells. In this complex web of interactions, several studies have addressed the immunomodulatory and neurological effects of odorants.

Other previous works have also shown a correlation between the loss of the sense of smell and the appearance of the first symptoms of Alzheimers disease.

We have focused on the olfactory systems role in the immune and central nervous systems, and we have confirmed that menthol is an immunostimulatory odor in animal models.

But, surprisingly, we observed that short exposures to this substance for six months prevented cognitive decline in the mice with Alzheimers and, what is most interesting, also improved the cognitive ability of healthy young mice, says DrJuan Jos Lasarte.

Another result noted by the researchers is that blocking the activity of T regulatory cells, one type of immune cells with immunosuppressive activity, also improved the cognitive ability of mice with Alzheimers disease and also caused a clear benefit in the cognitive ability of healthy young mice, explains Dr.Ana Garca-Osta.

Both menthol exposure and Treg cell blockade caused a decrease in IL-1b, a protein that could be behind the cognitive decline observed in these models. In addition, the specific blockade of this protein with a drug used in treating some autoimmune diseases also improved the cognitive capacity of healthy mice and mice with Alzheimers.

This study is an important step toward understanding the connection between the immune system, the central nervous system and smell, as the results suggest that odors and immune modulators may play an important role in the prevention and treatment of Alzheimers. and other diseases related to the central nervous system, points out Dr.Noelia Casares.

Funding: The Government of Navarra and the Ministry of Economy and Competitiveness financed this work. It is part of the Instituto de Investigacin Santiaria de Navarra (IdiSNA). It is also part of the INNOLFACT project, a multicenter consortium coordinated by Dr Enrique Santamara, a Navarrabiomed researcher.

This consortium aims to study the olfactory function in aging and develop new immunomodulatory therapies to slow down the development of neurodegenerative diseases.

Author: Miriam SalcedoSource: Universidad de NavarraContact: Miriam Salcedo Universidad de NavarraImage: The image is credited to Neuroscience News

Original Research: Open access.Improvement of cognitive function in wild-type and Alzheimers disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells by Casares Noelia et al. Frontiers in Immunology

Abstract

Improvement of cognitive function in wild-type and Alzheimers disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells

A complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimers Disease Mouse Models.

We first found that repeated short exposures to menthol odor enhanced the immune response against ovalbumin immunization. Menthol inhalation also improved the cognitive capacity of immunocompetent mice but not in immunodeficient NSG mice, which exhibited very poor fear-conditioning.

This improvement was associated with a downregulation of IL-1 and IL-6 mRNA in the brains prefrontal cortex, and it was impaired by anosmia induction with methimazole.

Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the APP/PS1 mouse model of Alzheimer. Besides, this improvement was also observed by the depletion or inhibition of T regulatory cells.

Treg depletion also improved the cognitive capacity of the APPNL-G-F/NL-G-FAlzheimers mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1 mRNA. Blockade of the IL-1 receptor with anakinra resulted in a significant increase in cognitive capacity in healthy mice as well as in the APP/PS1 model of Alzheimers disease.

These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for CNS-related diseases.

Link:
Menthol Inhalation May Boost Cognitive Ability in Alzheimer's - Neuroscience News

Neuroscience

High-Resolution Image of the Human Retina Reveals Stunning Details – Neuroscience News

Summary: Researchers developed a new imaging technique to visualize several dozen proteins in a thin tissue section at high resolution using fluorescence microscopy.

The technique enabled researchers to map the development of human retinal organoids at high temporal and spatial resolution, providing insights into how healthy tissue forms and developing a time series that describes the entire 39-week development of retinal organoids.

The researchers aim to apply this approach to other tissue types, such as the human brain and various tumor tissues, creating an atlas that provides information on the development of human organoids and tissues.

Key Facts:

Source: ETH Zurich

What cell types are found in which human tissue, and where? Which genes are active in the individual cells, and which proteins are found there?

Answers to these questions and more are to be provided by a specialized atlas in particular how the different tissues form during embryonic development and what causes diseases.

In creating this atlas, researchers aim to map not only tissue directly isolated from humans, but also structures called organoids. These are three-dimensional clumps of tissue that are cultivated in the laboratory and develop in a way similar to human organs, but on a small scale.

The advantage of organoids is that we can intervene in their development and test active substances on them, which allows us to learn more about healthy tissue as well as diseases, explains Barbara Treutlein, Professor of Quantitative Developmental Biology at the Department of Biosystems Science and Engineering at ETH Zurich in Basel.

To help produce such an atlas, Treutlein, together with researchers from the Universities of Zurich and Basel, has now developed an approach to gather and compile a great deal of information about organoids and their development. The research team applied this approach to the organoids of the human retina, which they derived from stem cells.

Many proteins visible simultaneously

At the heart of the methods the scientists used for their approach was the 4i technology: iterative indirect immunofluorescence imaging. This new imaging technique can visualize several dozen proteins in a thin tissue section at high resolution using fluorescence microscopy.

The 4i technology was developed a few years ago by Lucas Pelkmans, a professor at the University of Zurich and coauthor of the study that has just been published in the scientific journalNature Biotechnology.

It is in this study that the researchers applied this method to organoids for the first time.

Typically, researchers use fluorescence microscopy to highlight three proteins in a tissue, each with a different fluorescent dye.

For technical reasons, it is not possible to stain more than five proteins at a time. In 4i technology, three dyes are used, but these are washed from the tissue sample after measurements have been taken, and three new proteins are stained. This step was performed 18 times, by a robot, and the process took a total of 18 days.

Lastly, a computer merges the individual images into a single microscopy image on which 53 different proteins are visible. They provide information on the function of the individual cell types that make up the retina; for example, rods, cones, and ganglion cells.

The researchers have supplemented this visual information of retinal proteins with information on which genes are read in the individual cells.

High spatial and temporal resolution

The scientists performed all these analyses on organoids that were of different ages and thus at different stages of development. In this way, they were able to create a time series of images and genetic information that describes the entire 39-week development of retinal organoids.

We can use this time series to show how the organoid tissue slowly builds up, where which cell types proliferate and when, and where the synapses are located. The processes are comparable to those of retinal formation during embryonic development, says Gray Camp, a professor at the University of Basel and a senior author of this study.

The researchers published their image information and more findings on retinal development on a publicly accessible website:EyeSee4is.

Further tissue types planned

So far, the scientists have been studying how a healthy retina develops, but in the future, they hope to deliberately disrupt development in retinal organoids with drugs or genetic modifications.

This will give us new insights into diseases such as retinitis pigmentosa, a hereditary condition that causes the retinas light-sensitive receptors to gradually degenerate and ultimately leads to blindness, Camp says.

The researchers want to find out when this process begins and how it can be stopped.

Treutlein and her colleagues are also working on applying the new detailed mapping approach to other tissue types, such as different sections of the human brain and to various tumour tissues. Step by step, this will create an atlas that provides information on the development of human organoids and tissues.

Author: Press OfficeSource: ETH ZurichContact: Press Office ETH ZurichImage: The image is credited to Wahle et al. Nature Biotechnology 2023

Original Research: Open access.Multimodal spatiotemporal phenotyping of human retinal organoid development by Barbara Treutlein et al. Nature Biotechnology

Abstract

Multimodal spatiotemporal phenotyping of human retinal organoid development

Organoids generated from human pluripotent stem cells provide experimental systems to study development and disease, but quantitative measurements across different spatial scales and molecular modalities are lacking.

In this study, we generated multiplexed protein maps over a retinal organoid time course and primary adult human retinal tissue.

We developed a toolkit to visualize progenitor and neuron location, the spatial arrangements of extracellular and subcellular components and global patterning in each organoid and primary tissue. In addition, we generated a single-cell transcriptome and chromatin accessibility timecourse dataset and inferred a gene regulatory network underlying organoid development.

We integrated genomic data with spatially segmented nuclei into a multimodal atlas to explore organoid patterning and retinal ganglion cell (RGC) spatial neighborhoods, highlighting pathways involved in RGC cell death and showing that mosaic genetic perturbations in retinal organoids provide insight into cell fate regulation.

Read more here:
High-Resolution Image of the Human Retina Reveals Stunning Details - Neuroscience News

Internal Medicine

SMH Addiction and Internal Medicine Clinic caring for the whole … – Sheridan Media

The Sheridan Memorial Hospital Addiction and Internal Medicine Clinic utilizes the use of medications, in combination with counseling and other therapeutic techniques, to provide a whole-patient approach to the treatment of substance use disorders.

Successfully treating addiction for 10 years, Dr. Jason Ackerman, MD is the leader of the team at SMH Addiction and Internal Medicine Clinic and is board certified in Addiction and Internal Medicines.

Dr. Ackerman told listeners of Sheridan Medias Public Pulse program what the team and many other professionals define as addiction.

Utilizing the Medication Assisted Treatment (MAT) approach to treating addiction in partnership with Northern Wyoming Mental Health allows the SMH Addiction and Internal Medicine Clinic to treat the patient physically and mentally, including primary care.

In 2021, Wyoming suffered 71 opioid overdose deaths, accounting for 65% of all drug overdose deaths in the Cowboy State. Treating the medical concerns or problems of patients with an opioid addiction means addressing issues and treatments differently than traditional medicine may prescribe. The team at the SMH Addiction and Internal Medicine Clinic takes these factors into account and treats patients accordingly.

According to Dr. Ackerman, with the advances in medicine and modern knowledge, addiction can be treated like the disease it is while the patient retains their dignity as they continue their journey to a better life.

No referral is needed to make an appointment with the SMH Addiction and Internal Medicine Clinic, call 307-675-2674, or visit the Outpatient Center at 1333 West 5th St. Suite 200 in

Sheridan.

707

Read more here:

SMH Addiction and Internal Medicine Clinic caring for the whole ... - Sheridan Media

Internal Medicine

Irene Chernova is the 2023 Dostanic Award Recipient – Yale School of Medicine

Irene Chernova, MD, PhD, instructor of medicine (nephrology) has been selected as the recipient of the 2023 Iva Dostanic, MD, PhD, Physician-Scientist Trainee Award.

The Dostanic Award is presented to a physician-scientist who exemplifies the qualities of the late Iva Dostanic, MD, PhD, a trainee who left a mark on the department.

Chernova is the thirteenth awardee, and was co-nominated by Joseph Craft, MD, Paul B. Beeson Professor of Medicine (Rheumatology) and professor of immunobiology and Stefan Somlo, MD, C. N. H. Long Professor of Medicine (Nephrology) and professor of genetics; chief, Section of Nephrology.

She came to Yale for residency training in 2015, after graduating from the University of Pennsylvania MD/PhD program. Chernova completed residency training and fellowship in the ABIM Physician-Scientist Research Pathway and joined the faculty in 2022. Her current research is focused on lupus nephritis and autoimmune inflammation of the kidney.

The kidney is a very unique, hostile microenvironment. Ive been seeking to understand how immune cells that hurt the kidney are able to survive, where they have no business being under healthy circumstances, and the implications this has for therapy for patients, said Chernova.

Chernova developed a new line of research in the Craft Laboratory, exploring the role of ions and Na+-K+-ATPase on B cell survival. She demonstrated that this ion pump is required for B cell survival during renal ionic stress, with lupus B cells resistant to such Na+ induced death. Their resistance promotes intrinsic kidney damage and subsequent progression of nephritis. This novel physiological finding also explained for the first time why B cell depletion, in addition to its effect on autoantibody reduction, is therapeutically successful in lupus nephritis, said Craft.

I feel humbled to be recognized by those I admire tremendously at my own institution, and to meet the criteria of the award and all that Iva embodied.

After giving birth to her first child in mid-April, Chernova is set to give the Dostanic Award Lecture at Medical Grand Rounds in June, several months into maternity leave. I cant think of a better reason to come in during my leave, exclaimed Chernova.

She first told her husband and a few friends about being selected for the Dostanic award. Next thing she knew, her husband started an email with family and friends with the subject line, Pregnant and killing it! and the congratulations began pouring in.

As an only child of an immigrant family, Dostanics story resonates with Chernova. Chernova draws parallels with her own upbringing, having moved to the U.S. at the age of 10. And like Dostanic, Chernova was also recruited to the ABIM Physician-Scientist Research Pathway.

To Chernova, the award means more than winning a national one. I feel humbled to be recognized by those I admire tremendously at my own institution, and to meet the criteria of the award and all that Iva embodied.

The history of the award dates back to 2011 when Iva Dostanic, MD, PhD, was recruited to the ABIM Physician-Scientist Research Pathway in the Department of Internal Medicine.

Iva was extremely productive as an outstanding graduate student, earning her PhD in molecular genetics, biochemistry, and microbiology at the University of Cincinnati. She was first author of five papers in the field of cardiovascular physiology that were very novel at the time. She could have immediately taken a faculty position in a basic science department, but she wanted to be a physician, as well as a scientist. So she decided to attend medical school at the Cleveland Clinic Lerner College of Medicine, said Peter Aronson, MD, C.N.H Long Professor of Medicine (nephrology), who was involved in her recruitment.

Iva was a candidate who epitomized the best of being a physician and scientist.

Aronson was the program director of the Physician-Scientist Research Pathway from 2006-2011, and during the interview process Dostanic made an impression as an extraordinarily outstanding candidate. In addition to her research accomplishments as a graduate student, Iva excelled in her clinical studies in medical school, receiving the student award for excellence in the art and practice of medicine. Iva was a candidate who epitomized the best of being a physician and scientist, Aronson added.

The day before graduating medical school, Dostanic received devastating newsshe had ovarian cancer.

When Dostanic came to New Haven a month later after major surgery and initiation of chemotherapy, leadership knew that the workload of residency training would be far too physically demanding. Dostanic delayed her training due to her health and instead began a research fellowship in the Section of Pulmonary, Critical Care and Sleep Medicine in the lab of Patty Lee, MD.

While undergoing chemotherapy, Dostanic continued to work in Lees lab.

Iva researched how lung cells respond to hypoxia and started to identify what the hypoxia-related signal transduction mechanisms were in lung vascular cells, with the ultimate goal of identifying novel therapies for pulmonary hypertension a deadly disease with no cures, said Lee.

As Dostanics health declined, she was hospitalized at Yale New Haven Hospital (YNHH). Faculty visited with Dostanic and her parents, and she radiated positivity even during the most challenging times of her illness.

Jack Elias, MD, the Department of Internal Medicine chair at the time, knew that something had to be done for Dostanic. Many thoughts ran through his head on how to honor her.

I sat up at night thinking and an idea came to me that we should have an award for the physician-scientist trainee. When I mentioned this, it resonated with everyone and we went ahead and created it. And Iva was the first recipient, said Elias, Dean Emeritus and Warren Alpert Foundation Professor of Translational Science, Professor of Molecular Biology, Cell Biology and Biochemistry, Professor of Medicine at Brown University.

In December 2011, Dostanic lost her battle to cancer at the age of 35. Before passing, Dostanic received what became known as the inaugural Iva Dostanic, MD, PhD, Physician-Scientist Trainee Award in a ceremony held in her hospital room at YNHH.

She was my role modeldespite all the challenges she faced in the final years of her life, she emanated strength, an unstoppable passion for science, and joyful spirit.

The following June, Patty Lee described Dostanics research in the first Dostanic Award Lecture that Lee presented on behalf of Dostanic.

She was my role modeldespite all the challenges she faced in the final years of her life, she emanated strength, an unstoppable passion for science, and joyful spirit, said Lee, Professor of Medicine in the Division of Pulmonary, Critical Care & Sleep Medicine at Icahn School of Medicine at Mount Sinai.

Science was easy for Dostanica way of life. Not only did she excel in it, she loved it. Dragana Dostanic, Ivas mother, likened the lab to her kingdom. She would tell us about the feeling of taking the elevator to the lab. You cannot imagine that feeling, shed say. Science and medicine was a world worth exploring. She found it endlessly intriguing as she loved solving puzzles. It was her joy, her love, and it wasnt hard for her to devote long hours to her research.

Dostanic is described as someone who would brighten any room and a full human being by Mark Siegel, MD, director of Department of Internal Medicines Traditional Residency Training Program.

Beyond her accomplishments, Dostanics parents detail how kind and humble she was. Although she would not describe herself that way, and she was not one to talk about her achievements. Iva was uniqueshe found beauty in everything and good in everyone. Every moment was a time for celebration, even from an early age.

Iva was uniqueshe found beauty in everything and good in everyone. Every moment was a time for celebration, even from an early age.

Each morning, Dostanic woke at 5 a.m and read scientific articles followed by going for a run. She loved restaurants, playing tennis and skiing, and also fashion. Dostanic was well dressed, put together and oftentimes sparked questions from others about where she was headed. Her response? Nowhere!

She spoke several languages and excelled at most things, but one thing she was not great at was singing. Dostanics parents recall laughing about how she could not carry a tune. That didnt stop her from singing though. When at the Cleveland Clinic she would enter the lab while belting out the national anthem, as she loved to make others laugh.

Iva had a great sense of humor. She took her work seriously, but not herself seriously, Dragana explained. A friend to all, Dostanic would uplift whoever she was around. Dragana describes how her daughter found beauty in each of her friends and that each person was a special gift to her.

And like most physician-scientists and scientists, Dostanic was concerned about funding. She was aware that her research depended on funding and always looked ahead to find new ideas for grants.

In 2015, Dostanics parentsDragana and Predrag Dostanicpledged their estate to Yale School of Medicine (YSM) to endow the Iva Dostanic, MD, PhD, Physician-Scientist Fund to support physician-scientist career development in her memory.

I think that she would fully approve that we support research and science. We strongly believe that she would want us to do what is important. The pain of losing her stays with us. You cannot beat the pain, you just learn how to live with it.

For them, it is a way to continue their daughters legacy.

Predrag explained, I think that she would fully approve that we support research and science. We strongly believe that she would want us to do what is important. The pain of losing her stays with us. You cannot beat the pain, you just learn how to live with it.

Sometimes I think she lived her life as if she was aware it would not be long. She was a fast burning star, Dragana shared.

Since over a dozen individuals have been selected for the honor, Dostanic and her story continue to have an impact.

The award in Ivas name has provided a small measure of consolation for all of us at Yale who knew her to find meaning in the devastating loss of this exceptional young woman, said Aronson.

Each December, the department announces a solicitation for nominations with a deadline for submission at the end of January or beginning of February. A physician-scientist is selected by a committee shortly thereafter, and the recipient receives the award and presents the award lecture on a research topic of their choice at Medical Grand Rounds (MGR) in June. The awardee is also recognized at a dinner the preceding evening.

Prior to the pandemic, the Dostanics would visit New Haven for the awardees MGR each June. This June will be the first year the Dostanics are joining in person since 2019. I see Iva in each and every one of the recipients. I see this spark, this intelligence, this enthusiasm, I see her. I see her and I'm so happy to see that, said Dragana.

Winning the award was a really nice opportunity to meet the Dostanic family, as they believe in the physician-scientist training modality.

Aspiring physician-scientists should know that being a physician-scientist is truly a labor of love. There are many, many challenges inherent to this career decision, said Daniel Jane-wit MD/PhD.

Iva Dostanic was such a talented and dedicated physician scientist that to be recognized with her award was very humbling and an honor. Out of the awards I've received, this one is the most meaningful to me because when I've had challenges in my career, I think of the challenges that Iva had and how her resilience and hard work never stopped her from accomplishing her goals. She was a true role model for early career investigators. She was certainly a role model to me.

Discipline determines destiny, not desire. To achieve your goals, you have to put your head down and do the work to forge your future rather than waiting for people to give you what you desire without actually putting in the work, said Jose Herazo-Maya, MD.

"Iva left an incredible legacy at YSM, as well as in my own section, and I was (and still am) deeply honored to have received an award in her name. It is an incredible honor to be recognized by one's own institution and colleagues, and this award was even more meaningful in light of Iva's legacy. The award gave me the chance to get to know Iva's wonderful parents, who I still look forward to seeing at the reception every year. The award also afforded me the opportunity to present at MGR, even though I had only joined the faculty the year prior, which was a wonderful opportunity to share my research with the department, said Lauren Ferrante, MD, MHS.

I wish I had the privilege of knowing Iva. I only learned about her inspiring life when I received this award. She was a young woman who had a genuine passion for science, for the scientific process. She loved the pursuit of scientific discovery and kept going despite the obstacles life threw her way. I was humbled and honored when I received the award. The award plaque is proudly displayed on my bookshelf in my office at work. Even though its been five years since I took this position at UT Southwestern, I have still yet to hang any of my other awards or diplomas in my office, or pictures for that matter. So the Dostanic Award plaque is a primary source of inspiration and constant reminder of Ivas spirit and perseverance.

Becoming an independent investigator and learning how to build and run a laboratory has been challenging, but also rewarding. Any time Im stressed about something or dealing with a challenge that at the time seems insurmountable, her memory gives me pause and the motivation to press on. I hope to honor Ivas memory by being a role model for future scientists by empowering young trainees and instilling a passion for science, said Sarah Huen, MD, PhD.

I never met Iva, but from what I learned about her, she was extremely driven, talented, focused, and a tremendous force for good. So, it means a lot to me to be associated with such a person. When I got the award, I had a chance to spend some time with her parentsgetting to know them, learning about Ivas life, and presenting my work at MGR. I think its motivated methinking about the many things she accomplished, and her tireless approach and work ethicit definitely helps me to push on when I face challenges, said Stephen Baldassarri, MD, MHS.

This award has been an incredible honor. Iva was the consummate physician-scientist, and her passion for research has continued to inspire me over the years. I feel privileged to be associated with her and the qualities she embraced, and thank Dragana and Predrag Dostanic for their generous contribution to the development of physician-scientists at Yale.

I would encourage trainees to find joy in their work, to persevere, and to embrace their individual journey through academic medicine, said Rupak Datta, MD/PhD, MPH.

Receiving this award in Iva Dostanics memory has meant so much to me. I am incredibly grateful, and it is truly one of my proudest achievements as a physician-scientist. This award has had a significant impact on my career development. The opportunity to present at MGR allowed me to share my work with a broad audience across the Department of Internal Medicine. It has also facilitated my ability to apply for career development awards. The values that Iva Dostanic embodied as a physician-scientist and her excitement, focus, and dedication inspire me. They are a reminder of why I do what I do daily, the love for science and passion for caring for and improving the lives of my patients.

Ivas story is so moving and inspirational. I am amazed by the impact that she has had on so many, including myself. It was such an honor to receive the award in her memory. I hope to pay tribute to her through my dedication to pursue translational research that can one day impact patient care. I also hope to always approach my research and patient care with the passion and joy that Iva Dostanic exemplified.

I would encourage other aspiring physician-scientists to surround themselves with strong mentors early in their careers. For me, this has included a multidisciplinary team of scientific advisors as well as mentors who have really supported me and guided me in my career development. The path of a physician scientist can be challenging at times, with various transitions, and having a good support system can make all the difference, said Ana Luisa Perdigoto, MD, PhD.

Iva was a force of nature; she persevered even when everything seemed to be falling apart. Her spirit of perseverance despite the odds is what I admire most. This award was not only an honor that helped me feel supported by the department, but also helped crystallize my thoughts regarding the potential of my work so that I can further hone my ideas and research direction. In the beginning of my career, it is easy to get excited about many different ideas, but the MGR was helpful in focusing my ideas and getting feedback so that I can identify areas where there may be more excitement that I could then capitalize upon. This award gave me encouragement to continue persevering in the pursuit of my research question.

Mentorship teams are key to navigating the ups and downs of an academic research career. We all stand on the shoulders of giants, who can show us the right directions to look, said Dennis Shung, MD, MHS, PhD.

As an intern at Yale, I remember sitting in the grand rounds where the Dostanic award was presented and being so inspired by Ivas story. Through residency and fellowship, I often thought of Ivas passion and her legacy. It was such an honor to have received this award and be recognized by ones own mentors and institution. This award has inspired me to promote the physician-scientist career and help junior trainees navigate this exciting, yet uncertain path, said Benjamin Goldman-Israelow, MD/PhD.

2012Iva Dostanic, MD, PhD, Pulmonary, Emerging Roles for Innate Immunity in Lung and Endothelium (presented by Patty Lee, MD)

2013Isaac Hall, MD, MS, Nephrology, Donor Kidney Quality and Acute Kidney Injury with Transplantation

2014Daniel Jane-wit, MD/PhD, Cardiology, "Translational Approaches for Studying Cardiac Allograft Vasculopathy"

2015Jose Herazo-Maya, MD, Pulmonary, Predicting Outcome in IPF: The Dawn of Genomic Biomarkers

2016Lauren Ferrante, MD, MHS, Pulmonary, Improving Post-ICU Outcomes: A Call to Action

2017Sarah Huen, MD, PhD, Nephrology, Acute Kidney Injury: Not All That is Inflammatory is Pathologic"

2018Stephen Baldassarri, MD, MHS, Pulmonary, Electronic Cigarettes: The End of Smoking or a Deadly New Addiction?

2019Shelli Farhadian, MD, PhD, Infectious Diseases, Neuroinflammation During Chronic HIV Infection

2020Rupak Datta, MD/PhD, MPH, Infectious Diseases, Antibiotic Stewardship to Promote Palliative Care in Older Adults Near the End of Life

2021Ana Luisa Perdigoto, MD, PhD, Endocrinology, Clinical and Preclinical Insights into the Mechanisms of Checkpoint Inhibitor-induced Diabetes

2022Benjamin Goldman-Israelow, MD/PhD, Infectious Diseases, Prime and Spike: A Novel Vaccination Strategy for Inducing Mucosal SARS-CoV-2 Immunity

2022Dennis Shung, MD, MHS, PhD, Digestive Diseases, Human+AI in Medicine

The Department of Internal Medicine at Yale is among the nation's premier departments, bringing together an elite cadre of clinicians, investigators, educators, and staff in one of the world's top medical schools. To learn more, visit Internal Medicine.

See the rest here:

Irene Chernova is the 2023 Dostanic Award Recipient - Yale School of Medicine

Internal Medicine

Alzheimer’s treatment Leqembi could cost Medicare up to $5 billion per year, study estimates – CNBC

The Alzheimer's drug Leqembi is seen in this undated handout image obtained by Reuters on Jan. 20, 2023.

Eisai | Reuters

The new Alzheimer's antibody treatment Leqembi could cost Medicare up to $5 billion per year, according to research published in a leading medical journal this week.

Medicare would spend about $2 billion per year if around 85,700 patients test positive for the disease and are treated with the Eisai and Biogen product Leqembi, according to the research published Thursday in JAMA Internal Medicine.

The program for seniors would spend $5 billion if around 216,500 patients become eligible for the breakthrough treatment, according to the study.

The authors said the estimated costs to Medicare are conservative and that spending on Leqembi might increase more than anticipated depending on demand and other factors.

The researchers who conducted the JAMA study included physicians and public health and policy experts. They are affiliated with the University of California Los Angeles, the Rand Corporation, Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, among other institutions.

Eisai and Biogen have priced the twice-monthly antibody infusions at $26,500 per year.

There are also additional annual costs estimated at $7,300 per patient associated with neurologist visits, MRI tests and PET scans, administration of infusions, and monitoring for and treatment of potential side effects, according to the researchers.

The study assumed Medicare would cover 80% of the costs, with patients left to pay the remaining 20% in full or in part depending on whether they have supplemental insurance.

Patients could face an annual bill of about $6,600 per year depending on the state they live in and whether they have supplemental insurance, according to the study. Some lower-income people who qualify for Medicare and Medicaid would pay nothing out of pocket.

Read CNBC's latest global health coverage:

The Alzheimer's Association, which lobbies on behalf of patients living with the disease, estimates Alzheimer's and other forms of dementia will cost the U.S. $345 billion this year. Those costs could rise to $1 trillion by 2050, according to the association.

"That's the case without treatment. Prevention and treatment is the only path toward reducing this cost over time," Robert Egge, the association's head of public policy, said in a statement.

"But it's not cost that should determine if people have access to life improving care it's about the impact on people," Egge said. "Treatments taken in the early stages of Alzheimer's could mean a better quality of life."

Leqembi had a positive effect on patients with early Alzheimer's disease in clinical trial results published in the New England Journal of Medicine in January.

The expensive treatment is not available to the overwhelming majority of patients right now because Medicare has severely restricted coverage of the antibody.

Medicare has promised to provide broader coverage of Leqembi if the FDA grants full approval of the treatment in July. Leqembi received expedited approval from the Food and Drug Administration in January.

The Alzheimer's Association, members of Congress and state attorneys general are pushing for Medicare to drop its restrictions and fully cover Leqembi.

The antibody treatment, which targets brain plaque associated with the disease, slowed cognitive decline by 27% in Eisai's clinical trial.

There are currently no other drugs on the market that have demonstrated this level of efficacy at slowing Alzheimer's disease. Eli Lilly's donanemab demonstrated promising clinical trial results earlier this month. The company plans to apply for full FDA approval this quarter.

Leqembi and donanemab both carry serious risks of brain swelling and bleeding.

View post:

Alzheimer's treatment Leqembi could cost Medicare up to $5 billion per year, study estimates - CNBC

Internal Medicine

Capital Area Health Consortium Honors UConn Health Nurse … – University of Connecticut

The Capital Area Health Consortium, the group of Connecticut hospitals that employs medical residents and fellows in UConn-sponsored programs, announces honors for one fellow, one resident, and one nurse.

The consortium presented its Community Service Awards to Dr. Jasmin Hundal, an internal medicine fellow, and Dr. Joselyn Miller, an emergency medicine resident, and its T. Stewart Hamilton, MD, Fellowship Scholarship to Elizabeth Haskell, a quality assurance specialist.

Hundal is a graduate of UConns internal medicine residency and is the first to be accepted into the internal medicine fellowship program.

Dr. Hundal embodies the leadership our community expects from physicians, according to her nomination, submitted by Dr. Robert Nardino and Dr. Jacyln Cox, who lead the internal medicine residency program. She serves as a role model for young physicians and medical students. She goes above and beyond to bring together residents and students from different backgrounds to share a common cause of serving our community at a time when it is needed more than ever.

Her nominators say Hundal has demonstrated leadership in health equity throughout her residency and fellowship, citing examples including educating peers about disparities in medicine, organizing a Grand Rounds on responding to patient bias, and leading efforts to assist the homeless and those struggling with poverty or hunger.

Receiving this award is an honor that deeply resonates with my commitment to our community, both inside our hospital and out in the wider world, Hundal says. This recognition underscores the importance of our work in the health equity track, which Ive been privileged to steer. I express my profound gratitude to my mentors: Drs. [Kirsten] Ek, [Christopher] Steele, [Robert] Nardino, [Steven] Angus, and [Eric] Mortensen. Their guidance and support from the onset have been fundamental to my growth and achievements. This award not only validates our collective efforts but also renews my dedication to advancing health equity, making a meaningful difference in the lives we touch.

Miller is credited with sharing her perspective as a Black female physician and mentoring the next generation of residents.

She has visited local magnet schools to help provide guidance to underrepresented students starting their journey towards becoming medical professionals, Dr. Shawn London and Dr. Cynthia Price, who lead the emergency medicine residency program, write in their nomination. She is a kindhearted and thoughtful individual who has, in addition to her volunteer efforts in the greater Hartford area and in the medical student realm, dedicated a large amount of additional effort as co-chair of the UConn Resident and Fellows Forum in the 2022-23 academic year,

Her examples of community service include organizing an event for residents and fellows to create toys and blankets for the Animal Foundation, volunteering as a medical support physician at the Connecticut SWAT Challenge, and volunteering on the panel for the America Medical Womens Association to help female students strategize their career goals.

Haskell is applying the scholarship to her study in UConns Adult-Gerontology Acute Care Nurse Practitioner Program, which she started in the fall. Shes been a UConn Health nurse for the last seven years, during which time shes worked in the emergency department, intensive care unit, and cardiac catheterization lab before moving into her quality assurance role, which focuses on sepsis prevention.

Liz maintains a strong clinicians perspective, demonstrated by her ongoing review of evidenced based practice related to sepsis, as well as her continual study of sepsis related core measures, writes her nominator, Michelle DeLayo, director of critical care, advanced practice staff, and patient quality and safety. The SEP1 core measure is challenging and complex, but Liz collaborates closely with our core measure quality assurance nurse to audit patients in the institution in real-time to improve compliance with the metrics. Liz has developed a process to identify and follow patients that present with potential and actual sepsis and works directly with the care teams from admission to discharge to ensure the patients are provided optimal care.

DeLayo also credits Haskell with being among the first to volunteer to assist with the surge of patients during the COVID pandemic, offering to take additional shifts, and providing critical care education to those who were helping in the ICU.

I am honored to be a recipient of the T. Stuart Hamilton, MD, Fellowship Scholarship, Haskell says. It means a lot to me to be supported as I pursue an advanced degree and overcome the barriers of being a working mother and first-generation college graduate. I hope to inspire others to do the same.

The six-hospital Capital Area Health Consortium administers the salary and benefits to all the residency and fellowship programs the UConn School of Medicine sponsors. It also provides educational seminars to residents and fellows to help them plan life after residency.

The member hospitals include UConn John Dempsey Hospital, Connecticut Childrens, Hartford Hospital, the Hospital of Central Connecticut, the Hospital for Special Care, and Saint Francis Hospital and Medical Center.

Go here to see the original:

Capital Area Health Consortium Honors UConn Health Nurse ... - University of Connecticut