Thursday, February 02, 2023

RACIST MEDICINE U$A

Lifestyle biomarker linked to high blood pressure, increased stroke risk among Black adults


American Stroke Association International Stroke Conference 2023, Abstract 83

Reports and Proceedings

AMERICAN HEART ASSOCIATION

Research Highlights:

  • Researchers have identified a lifestyle-related biomarker called gluconic acid that may be a target to reduce stroke risk in Black adults.
  • Higher levels of gluconic acid in the blood were associated with high blood pressure and increased risk of ischemic stroke among Black adults when compared to white adults.
  • Among Black adults, a higher level of gluconic acid was associated with a Southern diet (foods high in added fats, fried foods, processed meats and sugary drinks), a lower level of education and a lack of exercise.

Embargoed until 4 a.m. CT/5 a.m. ET, Thursday, Feb. 2, 2023

DALLAS, Feb. 2, 2023 — Researchers have identified a lifestyle-related metabolite biomarker called gluconic acid that is associated with high blood pressure, increased risk of ischemic stroke, eating a Southern diet, lower level of education and lack of exercise, among Black adults, according to preliminary research to be presented at the American Stroke Association’s International Stroke Conference 2023. The meeting, to be held in person in Dallas and virtually Feb. 8-10, 2023, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

According to the American Stroke Association, a division of the American Heart Association, stroke is one of the leading causes of death and disability in the U.S., and African Americans have long experienced a higher rate of stroke. Currently, researchers are investigating new risk factors such as variations in blood levels of metabolites that might explain these differences. Metabolites are substances in the blood produced while exercising or in the breakdown of food and medications during metabolism.

“We have identified a biomarker called gluconic acid that we believe is a lifestyle-related biomarker, providing a direct link to diet and exercise,” said Naruchorn Kijpaisalratana, M.D., Ph.D., lead study author and a research fellow in neurology at Massachusetts General Hospital in Boston. “Gluconic acid may be considered as a dietary-related oxidative stress marker due to its availability in food, potentially produced by the gut microbiome, and related to diseases with oxidative stress. We think that this biomarker may provide a pathway to improve diet and exercise habits to help prevent a future stroke.“

The study analyzed health data for more than 2,000 people participating in the Reasons for Geographic and Racial Difference in Stroke (REGARDS) study. The ongoing REGARDS study has enrolled more than 30,000 Black and white adults since 2003 from the Southeastern U.S., known as the “stroke belt,” and other states across the country. The aim of REGARDS is to investigate the reasons for the high rate of stroke among African Americans.

This new analysis included 1,075 ischemic stroke survivors during a mean follow-up period of 7 years. Of those, 439 were Black adults and 636 were white adults (mean age of 70 years; 50% female). A random comparison group drawn from study participants consisted of nearly 1,000 Black adults and white adults who had not had a stroke (mean age of 65 years; 55% female).

The samples used in this study were collected from REGARDS participants over a 4-year period of enrollment (from 2003 to 2007). Using the samples, researchers extracted and measured levels of 162 metabolites in the blood of the participants. The data analysis examining the association between these metabolite levels and high blood pressure and future risk of ischemic stroke in both the Black and white adults was performed in 2021-2022.

The study found:

  • Of the 162 metabolites that were measured, elevated levels of the metabolite gluconic acid were found in Black adults who had high blood pressure but not their white peers with high blood pressure.
  • Black adults with the highest gluconic acid levels were 86% more likely to have high blood pressure.
  • Black adults with the highest gluconic acid levels had a 53% increased risk of ischemic stroke. No such association was found for white participants.
  • Gluconic acid accounted for 25% of the association between high blood pressure and stroke among Black adults.
  • In Black adults, after adjusting for multiple factors, a higher level of gluconic acid was associated with a Southern diet (foods high in added fats, fried foods, processed meats and sugary drinks), a lower level of education and a lack of exercise.

The researchers suggest that a blood test measuring metabolites may be able to determine if diet and exercise are working to lower stroke risk. “In the future, we envision that a metabolite like gluconic acid may be used as a biomarker to inform health care professionals whether the patient is eating healthy enough or exercising enough,” Kijpaisalratana said. “A biomarker like gluconic acid may point individuals toward more targeted guidance for stroke prevention.”

A limitation of the study was that the participants had high blood pressure at the beginning of the study, so researchers were not able to track the condition as it developed.

“Given the longstanding, higher risk of stroke among Black versus white adults in the United States — which is still not fully explained by a higher frequency of traditional stroke risk factors — the discovery of a new, potential prognostic marker or therapeutic target is very important,” said Bruce Ovbiagele, M.D., M.Sc., M.A.S., M.B.A., M.L.S., FAHA, American Heart Association expert volunteer and associate dean and professor of neurology at the University of California, San Francisco and chief of staff at the San Francisco Veteran Affairs Health Care System. “Since previous studies have found that culturally tailored lifestyle educational approaches may help to improve blood pressure control in Black adults, gluconic acid might serve as an objective measure to inform health care professionals about how well their patients are doing reducing hypertension and stroke risk and may also be helpful to motivate Black patients to modify their lifestyles as appropriate to prevent stroke.”

Ovbiagele, who was not involved in this study, also noted that future studies will need to examine the relationship between gluconic acid and the known social determinants of cerebrovascular health, including psychosocial stress and stroke risk, among Black adults compared to their white counterparts. Additional research will also need to explore whether this relationship holds true for recurrent stroke risk, too, since about one out of four strokes is a recurrent stroke.

Co-authors are Zsuzsanna Ament, Ph.D.; Amit Patki M.D.; Varun Mahesh Bhave, M.D.-candidate; Ana-Lucia Garcia Guarniz, M.D.; Suzanne E. Judd, Ph.D.; Mary Cushman, M.D., M.Sc.; Leann Long, Ph.D.; Marguerite M. Irvin, Ph.D.; and W. Taylor Kimberly, M.D., Ph.D. Authors’ disclosures are listed in the abstract.

The study was funded by the National Institutes of Health and the American Heart Association.

Statements and conclusions of studies that are presented at the American Heart Association’s scientific meetings are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association’s scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here.

Additional Resources:

The American Stroke Association’s International Stroke Conference (ISC) is the world’s premier meeting dedicated to the science and treatment of cerebrovascular disease. ISC 2023 will be held in person in Dallas and virtually, Feb. 8-10, 2023. The three-day conference will feature more than a thousand compelling presentations in categories that emphasize basic, clinical and translational sciences as research evolves toward a better understanding of stroke pathophysiology with the goal of developing more effective therapies. Engage in the International Stroke Conference on social media via #ISC23.


Black and Hispanic people in U.S. less likely to get treatment for stroke complications

American Stroke Association International Stroke Conference 2023, Abstract 146

Reports and Proceedings

AMERICAN HEART ASSOCIATION

Research Highlights:

  • Analysis of 20 years of data found Black and Hispanic adults in the U.S. were less likely to be treated for certain complications, such as depression and muscle stiffness, after a stroke compared to their white peers.
  • The greatest difference in the treatment of complications among Black and Hispanic stroke survivors occurred mainly within two weeks after a stroke.

Embargoed until 4 a.m. CT/5 a.m. ET, Thursday, Feb. 2, 2023

DALLAS, Feb. 2, 2023 — Analysis of 20 years of electronic health records across the U.S. finds Black and Hispanic stroke survivors were less likely than white stroke survivors to receive treatment for common complications during the first year after their stroke, according to preliminary research to be presented at the American Stroke Association’s International Stroke Conference 2023. The meeting, to be held in person in Dallas and virtually Feb. 8-10, 2023, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Despite increases in recent decades in the overall stroke survival rates in the U.S., Black and Hispanic adults in the U.S. still consistently fare worse in their recovery from a stroke when compared to their peers who are white. According to a new study, differences in the treatment of complications immediately after a stroke may possibly explain these persistent health disparities.

“A constellation of symptoms may manifest after a stroke; however, not all complications are life-threatening events. Some complications may be more subtle and go undetected by the medical community and, as a result, people from different racial or ethnic groups may not receive equitable treatment,” said lead study author “Stroke may have a devastating impact on an individual’s quality of life, and I think we owe it to our patients to do what we can to improve their level of function and quality of life after a stroke.”

In this study, Using electronic medical records from 65 large health care centers across the U.S., the analysis included patients hospitalized with stroke between August 2002 and July 2022. The records were divided into three patient groups (Black, non-Hispanic white and Hispanic): 80,564 Black stroke survivors were matched to 80,564 non-Hispanic white stroke survivors; and 28,375 non-Hispanic white stroke survivors were matched to 28,375 Hispanic stroke survivors. All participants were older than 18 years with an average age of 64 and 54% were male.

Stroke survivors were matched based on 41 factors that may affect recovery, including age, sex and other health conditions, such as hypertension and diabetes (Type 1 and 2). After matching there were no significant group differences for any of 41 factors. For the analysis, researchers reviewed medications prescribed for six common stroke complications: central nervous system arousal/fatigue (foggy brain function); mood irregularities (depression/anxiety); spasticity (muscle stiffness); sleep problems; bladder incontinence; and seizure. They then compared the differences in the treatment of these conditions after a stroke among the people who had these complications at three points in time: 14 days, 90 days and 365 days after the stroke.

The analysis revealed:

  • Black stroke survivors were significantly less likely to be treated for any complications except seizure, compared to stroke survivors who were white. The largest difference was seen in the treatment of arousal/fatigue, spasticity, and mood at the 14-day mark. Compared to stroke survivors who were white adults, those who were Black adults were 30% less likely to be treated for central nervous system arousal, 27% less likely to be treated for spasticity and 17% less likely to be treated for mood irregularities.
  • In the comparison of Hispanic vs. non-Hispanic white stroke survivors at the 14-day mark, Hispanics survivors were 20% less likely to receive treatment for central nervous system arousal; 19% less likely to receive treatment for spasticity; and 16% less likely to receive treatment for mood irregularities.
  • Little to no differences in the treatment of seizure were seen between the three patient groups at all three time periods.

“When a patient is having a seizure, the physical manifestations are often clear and demand urgent treatment. However, for other symptoms like foggy brain function or depression, health care professionals must dig a little deeper to assess for these signs or symptoms and determine if treatment is warranted. This difference between seizures and the other more subtle symptoms is the important take away,” Simmonds said. ”We found that the disparities among different population groups narrowed a little over time, and this likely shows that some of these conditions are being recognized and treated. However, even at the one-year mark, the overall treatment disparities remain for the treatment of nearly all post-stroke complications.”

The main limitation of this analysis is that a large database review like this can identify racial disparities in stroke care, however, it is less attuned to identify the specific factors driving them. “These differences are real and persistent, so it’s a matter of finding them, one by one, and filling these gaps,” Simmonds said.

The research team plans to test various intervention strategies that may help stroke survivors who are Black or Hispanic achieve a better functional recovery after their stroke.

“Communication moving forward is important. Many people survive their stroke, so health care professionals need to ask patients about these other subtle symptoms that may indicate additional complications, in addition to traditional risk factors such as blood glucose levels or blood pressure. These other domains have an important impact on our patients’ post-stroke, day-to-day quality of life.”

“It is very important for stroke survivors to receive treatment for subsequent complications. Successful recovery and quality of life depend upon the identification and management of post stroke complications,” said American Stroke Association, a division of the American Heart Association, volunteer expert Karen L. Furie, M.D., M.P.H., FAHA, vice chair of the Association Stroke Brain Health Science Subcommittee and professor and chair of neurology at the Warren Alpert Medical School of Brown University in Providence, Rhode Island. “Understanding the factors that contribute to these differences in treatment will empower clinicians to deliver high-quality, equitable care to stroke patients.” Dr. Furie was not involved in this study.

Co-authors are Folefac D. Atem, Ph.D.; Babu G. Welch, M.D.; and Nneka L. Ifejika, M.D., M.P.H. Authors’ disclosures are listed in the abstract.

No funding was reported for this study.

Statements and conclusions of studies that are presented at the American Heart Association’s scientific meetings are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association’s scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here.

Additional Resources:


Study finds Mexican American stroke survivors were less likely to receive intensive rehab


American Stroke Association International Stroke Conference 2023, Abstract WMP28

Reports and Proceedings

AMERICAN HEART ASSOCIATION

Research Highlights:

  • While previous research has indicated Mexican Americans have worse stroke outcomes, this study found they were more likely to have less intensive rehabilitation, such as home health and outpatient services, during the three months after their stroke compared to their non-Hispanic white peers.
  • Nearly one-third of all stroke survivors in the South Texas study, which included Mexican American adults, did not receive any type of rehabilitation within 90 days of their stroke.

DALLAS, Feb. 2, 2023 — Mexican American stroke survivors in a South Texas study, were more likely to use less intensive forms of rehabilitation services than their non-Hispanic white peers, and nearly one-third of all the stroke survivors did not receive any rehabilitation within 90 days of their stroke, according to preliminary research to be presented at the American Stroke Association’s International Stroke Conference 2023. The meeting, to be held in person in Dallas and virtually Feb. 8-10, 2023, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Even though stroke death rates among Mexican Americans are lower than their non-Hispanic white peers, previous research has shown that they often have worse outcomes and suffer greater disability after their stroke. One factor contributing to how well stroke survivors recover is the type of rehabilitation they receive in the window of time after the stroke, explained lead study author Lynda Lisabeth, Ph.D., M.P.H., a professor of epidemiology at the University of Michigan in Ann Arbor.

“The more intensive forms of stroke rehabilitation that are provided at inpatient or skilled nursing facilities have better outcomes than less intensive forms of rehabilitation,” Lisabeth said. “Our objective was to identify what factors may impact the type of rehabilitation a person gets. We want to know if there are barriers to getting the most intensive level of rehabilitation, then we can develop interventions that target those barriers, which will help to maximize rehabilitation across the board and potentially reduce these disparities.”

Researchers examined the link between ethnicity and the use and type of rehabilitation accessed by stroke survivors during the first 90 days after a stroke. They enrolled 554 participants from a South Texas community in the Brain Attack Surveillance in Corpus Christi Project (BASIC) soon after their stroke. Two-thirds of the participants were Mexican American adults (66%), and one third were non-Hispanic white adults. Nearly half were women, and the median age was 66 years.

The study was conducted between 2019 and 2021. During this period researchers conducted telephone interviews to determine the type of rehabilitation the stroke survivors received after hospital discharge, such as: outpatient, home health, inpatient or a skilled nursing facility. Participants were called every two weeks for three months and asked about their care. Based on in-person and telephone interviews, assessments were made of functional ability and depression at 90 days, along with information about the type of post-discharge care received.

The study found:

  • One-third of all study participants did not receive any type of rehabilitation during the three months after their stroke.
  • Two thirds (67%) of Mexican American stroke survivors, compared to just over half (56%) of non-Hispanic white peers, received some form of post stroke rehabilitation.
  • Mexican American stroke survivors were younger (median age of 65 vs. 70 for non-Hispanic whites), had lower levels of education and income, more health problems, higher average body mass index, and worse functional outcome and depression at 90 days compared to non-Hispanic white peers in this study.
  • After accounting for multiple factors such as age, income and other health conditions, Mexican American stroke survivors had almost two times higher odds of using any rehabilitation than non-Hispanic white stroke survivors.
  • Mexican American stroke survivors were more likely to use outpatient (11% vs. 5%, respectively) and home health rehabilitation (38% vs. 30%, respectively) when compared to their non-Hispanic white peers.
  • There were no major differences in the use of inpatient rehabilitation and skilled nursing facilities between the Hispanic and non-Hispanic white groups.

“There are many factors that drive the type of rehabilitation stroke survivors receive or if they can access rehabilitation. We want to better understand the barriers and preferences of Mexican American stroke survivors, so we may help develop culturally sensitive interventions that may increase the chances of stroke survivors going to inpatient rehabilitation, which contributes to better recovery,” Lisabeth said.

The study is limited by its small size and its focus on one community in South Texas (Nueces County, Texas), which suggests these results may not apply to other communities across the country. “This community has a higher proportion of Mexican American people in an urban setting with a unique availability of rehabilitation. The study also took place over a period of time that overlapped with the COVID-19 pandemic,” Lisabeth said.

The researchers note future studies focused on barriers and facilitators to intensive rehabilitation, especially among Mexican American stroke survivors, may be a way to reduce disparities and make substantial improvements in recovery.

The American Heart Association/American Stroke Association’s 2021 Clinical Performance Measures for Stroke Rehabilitation: Performance Measures were developed to focus on key aspects of stroke rehabilitation that are important to maintaining quality of care for stroke patients. They cover various aspects of stroke rehabilitation in the acute, post-acute inpatient, outpatient and home settings.

According to those measures, stroke is among the most common causes of acquired disability among adults in the United States, with more than 7 million Americans over 20 years of age having experienced a stroke in the past and almost 2.5% of Americans reporting that they are disabled as a result of stroke. People in the U.S. discharged from the hospital after stroke received their rehabilitation care at either an inpatient rehabilitation facility (19%), skilled nursing facility (25%) or through home care services (12%).

“Rehabilitation after a stroke is a key factor in recovery and the return to independent functioning,” said Joel Stein, M.D., FAHA, chair of the writing group for the American Heart Association/American Stroke Association clinical performance measures and the Simon Baruch Professor and chair of the department of rehabilitation and regenerative medicine at Columbia University’s Vagelos College of Physicians and Surgeons; professor and chair of the department of rehabilitation medicine at Weill Cornell Medicine; and physiatrist-in-chief at NewYork-Presbyterian Hospital. “Exploring differences in care and disparities is an essential method of understanding gaps in care and improving systems of care for stroke survivors. Many factors may influence the delivery of rehabilitation care post-stroke. Stroke survivors with substantial impairments who have fewer financial resources and less social support may struggle with direct discharge from the hospital to home.” Dr. Stein was not involved in this study.

Co-authors are Madeline Kwicklis, M.S.; Elizabeth Almendarez, Ph.D.; Janet Prvu-Bettger, Sc.D., FAHA; and Lewis B. Morgenstern, M.D., FAHA. Authors’ disclosures are listed in the abstract.

The study was funded by the National Institutes of Health.

Statements and conclusions of studies that are presented at the American Heart Association’s scientific meetings are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association’s scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here.

Additional Resources:

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New research turns what we know about bird window strikes inside-out

Researchers at William & Mary demonstrate that bird decals must be placed on the outside of windows to deter bird collision

Peer-Reviewed Publication

PEERJ

January 17, 2923 (Williamsburg, VA) - New research from William & Mary published in PeerJ Life & Environment reveals that decals intended to reduce incidents of bird window strikes—one of the largest human-made causes of bird mortality— are only effective if decals are placed on the outside of the window. Researchers found that the patterns on the films and decals placed on the internal surface of windows do not reduce collision because they may not be sufficiently visible to birds.


Bird window strikes occur when a bird flying near a building cannot perceive a glass windowpane and flies into it. These strikes are a significant concern for bird enthusiasts and conservationists, many of whom advocate for applying visibly noticeable films, patterns, and decals on surfaces of windows to alert birds of the glass.

Many people sympathetic to the potential of bird strikes around their homes or offices tend to apply decals to the inside of their windowpanes, primarily because external application is often logistically difficult and economically prohibitive, especially if the windows are above the first floor of a building. However, the results of this new study show that only external application of these decals can be associated with greater reductions in both window collisions and avian mortality.


Dr. John P. Swaddle, of William & Mary’s Institute for Integrative Conservation worked with students Blythe Brewster, Maddie Schuyler, and Anjie Su, to perform the first experimental study to compare the effectiveness of two distinct window films when applied to either the internal or external surface of double-glazed windows. The research team tested two different window film products: BirdShades and Haverkamp. These products were selected for the test because they engage with different wavelenths of light and colors visible to many songbirds.

Funding for the test of the BirdShades window film was provided by BirdShades Innovation GmbH. Using these films, the research team tested the avoidance of window collisions by zebra finches through controlled aviary flight trials. The team employed a design that allowed isolation of the effect of the window treatments on avoidance flight behaviors. A fine mist net in front of the windows prevented actual bird collision during the tests.

The team found consistent evidence that when applied to the external surface of windows, the films resulted in reduced likelihood of collision. However, neither product was effective when the films were applied to the internal surface of windows. Therefore, the results of this research demonstrate the imperative that installers apply these products to exterior surfaces of windows to maximize their protective benefits and reduce the risk of daytime window collision.

“Many people want to reduce bird-window collisions, as these unfortunate events kill hundreds of millions of birds each year,” says Dr. Swaddle. “There are lots of decals and window films that will likely make glass surfaces more visible to birds, decreasing collision risk. We were able to show that people must apply decals and films to the external surface of their windows to benefit the birds. We want people to know this as we want their time and money to be well spent—protecting the birds we all love.” Swaddle added “This research was conducted with a team of William & Mary undergraduate researchers, demonstrating the caliber of William & Mary students and the promise of the next generation of conservation
researchers."

PeerJ is an Open Access publisher of seven peer-reviewed journals. PeerJ’s mission is to give researchers the publishing tools and services they want with a unique and exciting experience. All works published by PeerJ are Open Access and published using a Creative Commons license (CC-BY 4.0). PeerJ is based in San Diego, CA and the UK and can be accessed at peerj.com.

In 2022 PeerJ is celebrated its first decade of publishing and innovation.

PeerJ is the peer-reviewed journal for Biology, Medicine and Environmental Sciences. PeerJ has an Editorial Board of over 2,000 respected academics. PeerJ Media Resources (including logos) can be found at: peerj.com/about/press

Notes to editor:
1. Research article:
Authors: John P. Swaddle, Blythe Brewster, Maddie Schuyler, Anjie Su
"Window films increase avoidance of collisions by birds but only when applied to external compared with
internal surfaces of windows”. PeerJ.
DOI: 10.7717/peerj.14676
This article is available at the Journal website https://peerj.com/articles/14676/ (after embargo 02 Feb)
2. Study Image: Swaddle, John.2022.birdstriketest.moviestill.jpeg

JOURNAL

PeerJ

DOI

10.7717/peerj.14676 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Window films increase avoidance of collisions by birds but only when applied to external compared with internal surfaces of windows

ARTICLE PUBLICATION DATE

2-Feb-2023

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SIXTY YEARS LATE(R)

UC Davis establishes Institute for Psychedelics and Neurotherapeutics

Business Announcement

UNIVERSITY OF CALIFORNIA - DAVIS

The University of California, Davis has launched the Institute for Psychedelics and Neurotherapeutics to advance basic knowledge about the mechanisms of psychedelics and translate it into safe and effective treatments for diseases such as depression, post-traumatic stress disorder, addiction, Alzheimer’s disease and Parkinson’s disease, among others. The new institute will bring together scientists across a range of disciplines and partner with the pharmaceutical industry to ensure that key discoveries lead to new medicines for patients. 

“Psychedelics have a unique ability to produce long-lasting changes in the brain that are relevant to treating numerous conditions,” said David E. Olson, associate professor in the Department of Chemistry and the Department of Biochemistry and Molecular Medicine at UC Davis. “If we can harness those beneficial properties while engineering molecules that are safer and more scalable, we can help a lot of people.”

Olson will be the founding director of the new institute, with John A. Gray, associate professor in the Department of Neurology, serving as associate director. In 2018, Olson and Gray published an influential study in Cell Reports demonstrating that psychedelics promote neuroplasticity — the growth of new neurons and formation of neural connections.  

“Neuronal atrophy is a key factor underlying many diseases,” said Gray, “and the ability of psychedelics to promote the growth of neurons and new connections in the brain could have broad therapeutic implications.”

A Historic Investment

The UC Davis institute will be funded in part by a contribution of approximately $5 million from the deans of the College of Letters and Science and the School of Medicine, the Vice Chancellor for Research and the Provost’s office. While other psychedelic science centers have been formed across the country with gifts from philanthropists, the UC Davis institute is notable for also being supported by substantial university funds.

“We wanted to put our money where our mouth is and demonstrate our commitment to this space,” said Estella Atekwana, dean of the College of Letters and Science overseeing the new institute. Additionally, philanthropic donations as well as grants and sponsored research agreements from the federal government, private foundations and industry partners will support the mission of the institute.  

“UC Davis has been leading the development of new medicines based on psychedelic research, and together with philanthropists, granting agencies and industrial partners, I’m confident that we can produce major benefits for society,” Atekwana said.

Leveraging strengths in chemistry, neuroscience and medicine

The institute will leverage the extraordinary breadth of expertise in the neuroscience community at UC Davis, which includes nearly 300 faculty members in centers, institutes and departments across the Davis and Sacramento campuses. Researchers will be able to work on every aspect of psychedelic science, from molecules and cells through to human clinical trials.

“Combining the considerable expertise of UC Davis’ pioneering basic research teams, world-class neuroscientists and our nationally recognized medical center is a formula for success that we trust will result in groundbreaking discoveries that will help patients regionally and worldwide,” said Susan Murin, dean of the School of Medicine who partnered with Atekwana to support the new institute.

The Institute for Psychedelics and Neurotherapeutics was specifically designed to facilitate collaborations across campus, such as that between Olson and Lin Tian, a professor in the Department of Biochemistry and Molecular Medicine. In 2021, their publication in Cell was voted the #2 biomedical research discovery of the year by STAT Madness.

A unique feature of the UC Davis institute will be its focus on chemistry and the development of novel neurotherapeutics. 

“Psychedelics have a lot of therapeutic potential, but we can do better,” said Olson. In 2020, his group published a paper in Nature describing the first non-hallucinogenic analogue of a psychedelic compound capable of promoting neuroplasticity and producing antidepressant and anti-addictive effects in preclinical models.  Olson calls these molecules psychoplastogens because of their effect on neuron growth.  Novel molecules tailored to specific disease indications could offer substantial benefits and open doors to partnerships with industry by solving many issues currently faced by traditional psychedelics related to safety, scalability, and intellectual property.

Bridging the Valley of Death between Academia and Industry

Major challenges exist for translating academic discoveries and promising lead compounds into drug candidates for clinical use. To bridge this gap, the institute aims to spin out companies and build strong collaborations with pharmaceutical partners through licensing and sponsored research agreements. Delix Therapeutics, a company co-founded by Olson, has licensed UC Davis technology and supported several cutting-edge basic research projects on campus related to psychoplastogens and neuroplasticity. Recently, Delix was named a top academic spinout company by Nature Biotechnology and C&E News, and in 2021, was named one of the Fierce 15 by Fierce biotech.  

“Our relationship with UC Davis has been very synergistic, and we are excited to continue that partnership,” said Mark Rus, the CEO of Delix. “Getting the brightest and most creative minds from academia and industry to work together is our best chance to solve many of the grand challenges facing society today.”


 






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AMERICAN JUNKIES

Scientists take another step toward building a better opioid


Scientists teamed up to publish detailed structures of the entire human opioid receptor family to guide the creation of more targeted pain medications.

Peer-Reviewed Publication

UNIVERSITY OF NORTH CAROLINA HEALTH CARE

peptide-bound opioid receptor 

IMAGE: ALIGNMENT OF PEPTIDE-BOUND OPIOID RECEPTORS REVEALS STRUCTURAL FEATURES, SUCH AS STERIC EFFECTS, THAT CONTRIBUTE TO THE SUBTYPE-SELECTIVE BINDING AND FUNCTIONAL OUTCOMES OBSERVED IN BIOCHEMICAL ASSAYS. view more 

CREDIT: ROTH LAB, UNC SCHOOL OF MEDICINE

CHAPEL HILL, NC – In the continuing effort to improve upon opioid pain relievers, American and Chinese scientists used cryoEM technology to solve the detailed structures of the entire family of opioid receptors bound to their naturally occurring peptides. Subsequent structure-guided biochemical studies were then performed to better understand the mechanisms of peptide-receptor selectivity and signaling drugs.

This work, published in Cell, provides a comprehensive structural framework that should help drug developers rationally design safer drugs to relieve severe pain.

This work was spearheaded by the lab of Eric Xu, PhD, at the CAS Key Lab of Receptor Research in China, in collaboration with the lab of Bryan L. Roth, MD, PhD, at the UNC School of Medicine, where graduate student Jeff DiBerto led the pharmacological experiments to understand the receptors’ signaling mechanisms.

Opioid drugs relieve pain by mimicking a naturally occurring pain-relief function within our nervous symptoms. They are the best, strongest pain relievers we have. Unfortunately, they come with side effects, some severe such as numbness, addiction, and respiratory depression, leading to overdose deaths.

Scientists have been trying for many years to overcome the side-effect problem in various ways, all involving one or more of four opioid receptors to no avail. One way scientists continue to explore is the creation of peptide or peptide-inspired small molecule drugs.

Peptides are short chains of amino acids; think of them as short proteins. Certain naturally occurring, or endogenous, peptides bind to opioid receptors on the surface of cells to create an analgesic effect, also known as pain relief. Think of an analgesic like an anesthetic, except that analgesics do not “turn off” the nerves to numb the body or alter consciousness. So, the idea is to create a peptide drug that has a strong analgesic effect, without numbing nerves or altering consciousness or causing digestive, respiratory, or addiction issues.

“The problem in the field is we’ve lacked the molecular understanding of the interplay between opioid peptides and their receptors,” said Roth, co-senior author and the Michael Hooker Distinguished Professor of Pharmacology. “We’ve needed this understanding in order to try to rationally design potent and safe peptide or peptide-inspired drugs.”

Using cryogenic electron microscopy, or cryoEM, and a battery of biomechanistic experiments in cells, the Xu and Roth labs systematically solved the detailed structures of endogenous peptides bound to all four opioid receptors. These structures revealed details and insights into how specific naturally occurring opioid peptides selectively recognize and activate opioid receptors. The researchers also used exogenous peptides, or drug-like compounds, in some of their experiments to learn how they activate the receptors.

The cryoEM structures of agonist-bound receptors in complex with their G protein effectors (called their “active state”) represents what these receptors look like when they are signaling in cells, giving a detailed view of peptide-receptor interactions. The Roth lab used the structures solved by the Xu lab to guide the design of mutant receptors, and then tested these receptors in biochemical assays in cells to determine how they alter receptor signaling. Understanding these interactions can then be used to design drugs that are selective for opioid receptor subtypes, as well as to produce certain signaling outcomes that may be more beneficial than those of conventional opioids.

“This collaboration revealed conserved, or shared, mechanisms of activation and recognition of all four opioid receptors, as well as differences in peptide recognition that can be exploited for creating subtype-selective drugs,” said DiBerto, first author and PhD candidate in the Roth lab. “We provide more needed information to keep pushing the field forward, to answer basic science questions we hadn’t been able to answer before now.”

Previous research showed the structure of opioid receptors in their inactive or active-like states, with active state structures only existing for the mu-opioid receptor subtype, the primary target of drugs like fentanyl and morphine. In the Cell paper, the authors show agonist-bound receptors in in complex with their G protein effectors, made possible through cryoEM technology that did not exist when currently used medications were being developed.

Drugs such as oxycontin, oxycodone, and morphine cause various effects inside cells and throughout the nervous symptom, including pain relief. But they have effects in the digestive and respiratory systems, too, and interact with cells to lead to addiction. Fentanyl, meanwhile, is another powerful pain reliever, but it binds to opioid receptors in such a way as to cause severe side effects, including the shutdown of the respiratory system.

The thrust behind such research led by Xu and Roth is to home in on the mechanistic reasons for pain relief potency without triggering the cellular mechanisms that lead to severe side effects and overdosing.

“We are attempting to build a better kind of opioid,” Roth says, “We’re never going to get there without these kind of basic molecular insights, wherein we can see why pain is relieved and why side effects occur.”

Co-first authors of the Cell paper are Yue Wang and Youwen Zhuang of the CAS Key Laboratory of Receptor Research and the State Key Laboratory of Drug Research at the Shanghai Institute of Materia Medica in the Chinese Academy of Sciences. Other authors are Edward Zhou and Karsten Melcher of the Van Andel Research Institute in Grand Rapids, MI, Gavin Schmitz and Manish Jain at the UNC School of Medicine, and Qingning Yuan, Weiyi Liu, and Yi Jiant at the CAS Key Laboratory.

UNC School of Medicine contact: Mark Derewicz

JOURNAL

Cell

DOI

10.1016/j.cell.2022.12.026 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Structures of the entire human opioid receptor family


New randomized trial shows simple letters promote better-informed opioid prescribing


Letters successfully encouraged clinicians to check patients’ prescribing records

Peer-Reviewed Publication

COLUMBIA UNIVERSITY'S MAILMAN SCHOOL OF PUBLIC HEALTH

Researchers reported new findings from a clinical trial of letters to promote safer and better-informed opioid prescribing. The study, which aimed to encourage clinicians to check on patients in a state database before prescribing them opioids, reported significant and durable gains toward this goal. The research will be published in the January issue of the journal Health Affairs.

The study enrolled clinicians who prescribed opioids with benzodiazepines or gabapentinoids. Taking these medications together can increase the risk of overdose. The researchers hypothesized that greater use of state prescription monitoring programs (PMPs), which track all prescriptions of these medications, could help clinicians avoid risky prescribing and safeguard their patients’ health. Nearly all states now run PMPs, but many clinicians still do not use them.

“PMPs could help clinicians prescribe opioids and other drugs more safely, but these databases will only move the needle if clinicians actually check them,” said Adam Sacarny, PhD of Columbia University Mailman School of Public Health, the study’s lead author. “Our research shows that simple letters can achieve that goal.”

To run the trial, the researchers partnered with the Minnesota Board of Pharmacy, which administers the PMP, and Minnesota Management and Budget Agency, which promotes the use of high-quality evidence to improve state decision-making. They enrolled 12,000 clinicians who prescribed opioids with benzodiazepines or opioids with gabapentinoids. The clinicians were then randomly assigned to a control group or to receive one of three types of letters: mandate letters focusing a new state requirement to check the PMP before prescribing opioids, information letters about their patients prescribed opioids with benzodiazepines or gabapentinoids, or combined letters that included both messages. The letters were sent in spring 2021.

Sacarny and co-authors analyzed the effects of the letters using de-identified data from the PMP. The data included all opioid, benzodiazepine, and gabapentinoid prescriptions dispensed throughout Minnesota, as well as all PMP account records and searches.

The researchers found that letters mentioning the mandate to check the PMP successfully increased engagement with the program. PMP search rates rose by 9 percent, and the effect persisted at least 8 months. The letters also encouraged clinicians to make PMP accounts, a prerequisite for searching. Effects were similar for the combined letters, which mentioned the mandate and also included prescribing information.

“The enduring impacts suggest that the letters encouraged engagement among clinicians who would not have otherwise created PMP accounts or searched the PMP. This finding is noteworthy because account creation is an important barrier to PMP use,” noted Mireille Jacobson, PhD, the study’s last author and associate professor of Gerontology at the University of Southern California.

The researchers note that other state PMPs or healthcare organizations could easily send similar letters as a part of a cost-effective evidence-based strategy to promote safer prescribing. Because the mandate letters contain no protected health information, they could also be sent over e-mail, further lowering the intervention cost.

The researchers detected no effects of the information letters, which did not focus on the new mandate to check the PMP. None of the letters led to detectable changes in prescribing.

“While the letters did not make a detectable difference in prescribing, we still think these results are encouraging,” noted Sacarny. “Letters focusing on the mandate successfully promoted PMP engagement through searching and account-holding, which meant clinicians had better access to key patient data as they decided on treatment.”

The study’s co-authors are Tatyana Avilova of the University of Tokyo, David Powell of the RAND Corporation, Ian Williamson and Weston Merrick of Minnesota Management and Budget, and Mireille Jacobson of the University of Southern California.

The study was supported by the Abdul Latif Jameel Poverty Action Lab and the National Institute for Health Care Management.

Columbia University Mailman School of Public Health

Founded in 1922, the Columbia University Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Columbia Mailman School is the fourth largest recipient of NIH grants among schools of public health. Its nearly 300 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change and health, and public health preparedness. It is a leader in public health education with more than 1,300 graduate students from 55 nations pursuing a variety of master’s and doctoral degree programs. The Columbia Mailman School is also home to numerous world-renowned research centers, including ICAP and the Center for Infection and Immunity. For more information, please visit www.mailman.columbia.edu.

JOURNAL

Health Affairs

DOI

10.1377/hlthaff.2022.00859 


Training nurses to fight against opioid addiction


Kennesaw State receives federal grant to implement curricular changes to increase access to early intervention


Grant and Award Announcement

KENNESAW STATE UNIVERSITY

Kennesaw State receives federal grant to train nurses in fight against opioid addiction 

IMAGE: KENNESAW STATE RESEARCHERS SUSAN BEIDLER AND KATHY BARNETT WILL INCORPORATE NEW CURRICULA INTO THE MASTER'S DEGREE PROGRAM TO ADDRESS DECREASING STIGMA AND INCREASING ACCESS TO EARLY INTERVENTIONS FOR SUBSTANCE USE DISORDERS. view more 

CREDIT: KENNESAW STATE UNIVERSITY

Kennesaw State University’s Wellstar School of Nursing has received a federal grant to teach graduate students how to help patients break increasingly deadly opioid addictions.

Assistant professor of nursing Kathy Barnett and Wellstar School of Nursing Associate Director of Graduate Programs Susan Beidler teamed to earn the nearly $729,000 grant, which comes from the Substance Abuse and Mental Health Services Administration (SAMHSA), a subsidiary of the U.S. Department of Health and Human Services (HHS). Barnett and Beidler will implement curricular revisions in the KSU Masters of Science in Nursing programs that address decreasing stigma and increasing access to early interventions for substance use disorders. 

“Opioid addiction is a growing problem in Georgia and across the United States and something Susan and I felt very strongly all our master’s students needed more expertise in,” said Barnett, who wrote her doctoral dissertation on substance use disorder. HHS has declared opioid addiction a public health emergency.

According to data from the Georgia Department of Public Health, drug overdose deaths increased by 61% from 2019 to 2021, and fentanyl-involved overdose deaths increased by 230%, illustrating the urgent need for more medical training in helping people with opioid addiction. Opioids include many prescription pain medicines, fentanyl and the illegal drug heroin.

KSU’s grant-funded program will cover 30 hours of instruction and will add another tool to the kit of nursing graduates from KSU in all three of the master’s degree tracks – education, administration and practice. Barnett said it shows the Wellstar School of Nursing’s commitment to reducing the negative impact of opioid use disorders.

“We do that by training more nurse practitioners and other master’s-prepared nurses in the treatment, assessment and referrals of those with opioid use disorders,” she said. “We're hoping that in our community there will be many more treatment options and more people that are trained solely in how to treat those with the disorders.”

The grant money will cover integration of the training components into the curricula, followed by evaluation via surveys of the impact of the program on students. Beidler, who joined the Wellstar School administration in 2021, after more than four decades teaching and practicing nursing, said KSU’s position at the forefront of nursing education in the state and region places the University perfectly to address addiction through this program.

“We’re not satisfied with the status quo. We’re always looking for creative and innovative ways for our graduates to be cutting-edge in their practice abilities, and this grant will add another tool to their ‘toolkit’ to address a critical public health problem in our communities,” Beidler said.


Combination therapy appears safe for treating opioid use disorder during pregnancy

Peer-Reviewed Publication

WILEY

Current guidelines recommend that pregnant women with opioid use disorder be prescribed either methadone or buprenorphine, but these drugs too have significant potential for abuse. A recent study published in Acta Obstetricia et Gynecologica Scandinavica indicates that combination therapy of buprenorphine and naloxone—which is known help to prevent such abuse—is as safe as buprenorphine alone during pregnancy for both mother and newborn.

In the study of 67 pregnant women, the buprenorphine-naloxone and buprenorphine groups showed similar outcomes and did not significantly differ from each other in terms of maternal health during pregnancies, deliveries, or newborn health.

“Combination therapy of buprenorphine and naloxone could be a choice for oral opioid maintenance treatment during pregnancy, but larger studies are needed before changing the official recommendations,” said corresponding author Minna M. Kanervo, of Helsinki University Hospital, in Finland. “Women on methadone treatment may have more severe substance abuse problems, so they require particularly cautious follow-up.”    

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1111/aogs.14497

 

Additional Information

NOTE: The information contained in this release is protected by copyright. Please include journal attribution in all coverage. For more information or to obtain a PDF of any study, please contact: Sara Henning-Stout, newsroom@wiley.com.

About the Journal
Published monthly, Acta Obstetricia et Gynecologica Scandinavica is an international journal dedicated to providing the very latest information on the results of both clinical and research work from around the globe. The journal regularly publishes commentaries, reviews and original articles on a wide variety of topics.

About Wiley
Wiley is one of the world’s largest publishers and a global leader in scientific research and career-connected education. Founded in 1807, Wiley enables discovery, powers education, and shapes workforces. Through its industry-leading content, digital platforms, and knowledge networks, the company delivers on its timeless mission to unlock human potential. Visit us at Wiley.com. Follow us on Facebook, Twitter, LinkedIn and Instagram.

JOURNAL

Acta Obstetricia Et Gynecologica Scandinavica

DOI

10.1111/aogs.14497 

ARTICLE TITLE


Buprenorphine-naloxone, buprenorphine, and methadone throughout pregnancy in maternal opioid use disorder

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