ReportWire

Tag: Embargoed Feed – hidden

  • Pathologic Scoring Shows Promise for Assessing Lung Tumor Therapy Response

    Pathologic Scoring Shows Promise for Assessing Lung Tumor Therapy Response

    [ad_1]

    **EMBARGOED UNTIL 8 P.M. ET SATURDAY, NOV. 4**

    Newswise — A new pathologic scoring system that accurately assesses how much lung tumor is left after a patient receives presurgical cancer treatments can be used to predict survival, according to new research led by investigators at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center and the Mark Foundation Center for Advanced Genomics and Imaging at the Johns Hopkins University.

    The study shows that pathologic assessment of residual viable tumor (RVT) in patients treated with immunotherapy and chemotherapy before lung cancer surgery provides a robust and efficient evaluation of patient treatment response that may be useful to guide patient therapy and predict survival. This latter finding supports pathologic evaluation of tumors as an early clinical trial endpoint and a surrogate of survival for potential accelerated regulatory approvals.

    The results were published on Nov. 4 in the journal Nature Medicine and simultaneously presented by senior study author Janis Taube, M.D., M.Sc., director of the Division of Dermatopathology at the Johns Hopkins University School of Medicine and a member of the Kimmel Cancer Center, at the Society for Immunotherapy of Cancer annual meeting in San Diego.

    Immunotherapies harness a patient’s immune system to target their tumors. These powerful drugs are often paired with conventional chemotherapies to help shrink a patient’s tumors before surgery, increasing the likelihood of successfully eliminating the cancer. To gauge treatment success, oncologists typically rely on radiologic imaging of the remaining tumor, but the results aren’t always as accurate in early-stage tumors as they are for more advanced cancers. More recently, circulating tumor DNA (ctDNA) clearance, which uses genetic sequencing to detect lung cancer-associated mutations in patient blood samples, has also shown promise, but is not yet widely available.

    For the new study, investigators performed a new analysis on data from the randomized, phase 3 CheckMate 816 study. That study found that treating presurgical non-small cell lung cancer patients with immunotherapy (nivolumab) plus chemotherapy improved event-free survival. This important surrogate endpoint can help predict long-term survival and pathologic complete response, which measures whether any tumor is left.

    “Most studies have focused on whether you have no tumor left or less than or equal to 10% of the tumor left, which is called a major pathologic response,” says lead study author Julie Stein Deutsch, M.D., an assistant professor of dermatology at Johns Hopkins.

    During the study, the investigators used a new approach, which measures residual tumor in patients who received neoadjuvant therapy, to predict outcomes in patients with a greater range of treatment responses. They used immune-related pathologic response criteria (irPRC) to look for pathologic changes that indicated the tumor had been present in the tissue before immunotherapy but was destroyed by the treatment, allowing them to measure what percentage of the tumor was left, or the RVT, ranging from 0% to 100%.

    As a result, they were able to separate patients into three groups based on how much tumor was left. In the future, data such as these may help guide the next round of clinical trials and ultimately help oncologists decide how to treat individuals in these subgroups, Deutsch says. For example, patients with no tumor left may be able to skip postsurgical immunotherapy or have a relatively limited amount, while individuals in the intermediate group may need to continue immunotherapy for longer. Those who showed a very limited response may need to switch to a new therapy or add a new therapy to their regimen. The team’s next steps will include identifying the most clinically meaningful cutoffs for RVT.

    They also looked beyond the primary tumor and used RVT to assess the immunotherapy effect on tumor in the lymph nodes, which showed additive value with the primary tumor for predicting survival. Long term, it may also be possible to strategically combine pathology, radiology and ctDNA results for the longitudinal monitoring of treatment efficacy.

    Already, the investigators demonstrated the pathologic scoring system can assess 10 types of tumors, including lung, skin and colorectal cancers, which could be another advantage over other tumor scoring systems.

    “The common features seen across these multiple tumor types means that pathologists don’t have to switch to different scoring systems for assessing pathologic response. This is similar to what already exists in radiology, where the RECIST system is used across all tumor types for determining objective response to therapy,” Taube says, noting that pathologists already are completing the necessary workflows as part of standard procedures when assessing surgically removed tumors. Assessing RVT is inexpensive and uses tools and supplies commonly used by pathologists, Deutsch says, which may also make it accessible for those working in low-resource settings.

    “It is important that as these immunotherapies move into clinical trials and become standard of care, pathologists worldwide have a standard scoring system for the assessment of treatment response,” Taube says. 

    Study co-authors were Ashley Cimino-Mathews, Elizabeth Thompson, Patrick M. Forde, Daphne Wang, Robert A. Anders, Edward Gabrielson, Peter Illei, Jaroslaw Jedrych, Ludmila Danilova and Joel Sunshine of Johns Hopkins. Other authors were from the Hospital Universitario Puerta de Hierro in Madrid, Spain; McGill University Health Center in Montreal, Canada; Institut du Thorax Curie-Montsouris in Paris, France; Aberdeen Royal Infirmary in the United Kingdom; Bristol Myers Squibb in Princeton, New Jersey; and Queen’s University in Kingston, Canada.

    The study was supported by Bristol Myers Squibb, Ono Pharmaceutical Company Ltd., the Bloomberg~Kimmel Institute for Cancer Immunotherapy, The Mark Foundation for Cancer Research and the National Institutes of Health (grant R01 CA142779).

    Deutsch is named on a patent for system and method for annotating pathology images to predict patient outcome (U.S. Provisional Patent Application 63/313,548, filed in Feb. 2022). Taube receives support for this study from Bristol Myers Squibb; receives consulting fees from AstraZeneca, Bristol Myers Squibb, Merck and Roche; participates on advisory boards from AstraZeneca; and is named on a patent for a machine learning algorithm for irPRC. These relationships are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

    [ad_2]

    Johns Hopkins Medicine

    Source link

  • Real-World Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients

    Real-World Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients

    [ad_1]

    Highlights

    • Compared with kidney transplant recipients who did not receive sodium-glucose cotransporter-2 inhibitors, those treated with the medications had lower risks of experiencing kidney transplant failure, kidney transplant rejection, major adverse cardiac events, all-cause mortality, and genitourinary infections.
    • Results from the study will be presented at ASN Kidney Week 2023 November 1–November 5. 

    Newswise — Philadelphia, PA (November 4, 2023) — Sodium-glucose cotransporter-2 (SGLT2) inhibitors lower blood sugar levels and have additional beneficial effects on kidney and heart health for individuals with and without diabetes, but little is known about the safety and efficacy of these medications in kidney transplant recipients. Research that examined this will be presented at ASN Kidney Week 2023 November 1–November 5.

    For the study, investigators analyzed the electronic medical records of 3,450 adult kidney transplant recipients treated with SGLT2 inhibitors who were matched to 3,450 similar patients who did not receive SGLT2 inhibitors, using a statistical technique called propensity matching adjusted for demographic data, baseline heart disease and blood test.

    Kidney transplant patients treated with SGLT2 inhibitors were 59%, 64%, 33%, and 40% less likely to experience kidney transplant rejection, kidney transplant failure, major adverse cardiac events, and mortality, respectively, over 3 years. They were also 44% less likely to experience urinary tract infections.

    “To date, all major SGLT2 inhibitor studies have excluded kidney transplant patients. This study was the largest observational study demonstrating the benefits of SGLT2 inhibitors in patients with kidney transplants,” said corresponding author Nageen, Anwar, MD, of the Liverpool University Hospitals NHS Foundation Trust. “This study is a big step towards qualifying transplant patients to benefit from the many positive effects of SGLT2 inhibitor use and sets the precedence for a randomized controlled trial to evaluate the long-term kidney and cardiovascular outcomes of SGLT2 inhibitor therapy in kidney transplant patients.” 

    Study: “Outcomes Associated with Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients: A Real-World Analysis Using a Global Federated Database” 

    The world’s premier nephrology meeting, ASN Kidney Week, brings together approximately 12,000 kidney professionals from across the world. The largest nephrology meeting provides participants with exciting and challenging opportunities to exchange knowledge, learn the latest scientific and medical advances, and listen to engaging and provocative discussions with leading experts in the field.

    About ASN

    Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge and advocating for the highest quality care for patients. ASN has nearly 21,000 members representing 140 countries. For more information, visit www.asn-online.org and follow us on Facebook, X, LinkedIn, and Instagram.

     

    # # #

     

     

    [ad_2]

    American Society of Nephrology (ASN)

    Source link

  • Does Your Neighborhood Affect Your Care After a Stroke?

    Does Your Neighborhood Affect Your Care After a Stroke?

    [ad_1]

    EMBARGOED FOR RELEASE UNTIL 4 P.M. ET, WEDNESDAY, NOVEMBER 1, 2023

    Newswise — MINNEAPOLIS – People who live in neighborhoods with lower socioeconomic status are less likely to receive clot-busting medications or undergo clot-removing procedures after they have a stroke than people who live in neighborhoods with higher socioeconomic status, according to a study published in the November 1, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.

    “These treatments can greatly reduce death and disability from stroke, but previous studies have shown that few people actually receive the treatments,” said study author Amy Ying Xin Yu, MD, of the University of Toronto in Canada. “We wanted to see how socioeconomic disparities play a role, especially in an area where everyone has access to universal health care.”

    The study looked at all people living in Ontario, Canada, who had an ischemic stroke during a five-year period, for a total of 57,704 people. Ischemic stroke is caused by a blockage of blood flow to the brain and is the most common type of stroke.

    The study looked to see how many of those people were treated with clot-busting drugs or surgery to remove blood clots.

    Researchers also looked at participants’ neighborhoods and divided them into five groups based on their neighborhoods’ socioeconomic status, which was determined by factors such as the percentage of adults without a high school diploma, unemployment rate and income level.

    A total of 17% of those living in the neighborhoods with the lowest socioeconomic status were treated, compared to 20% of those living in the neighborhoods with the highest socioeconomic status.

    When researchers took into account other factors that could affect treatment, such as age, high blood pressure and diabetes, they found that people in the neighborhoods with the lowest socioeconomic status were 24% less likely to be treated than people in the neighborhoods with the highest socioeconomic status. There was no difference in treatment between the neighborhood with the lowest status and the middle three neighborhoods.

    “Our study underscores the need for tailored interventions to address socioeconomic disparities in access to acute stroke treatments, including educational and outreach programs to increase awareness about the signs and symptoms of stroke in various languages and efforts to distribute resources more equitably across neighborhoods,” Yu said. “Further research is needed to examine the specific causes of these disparities, so we can find ways to address the larger systemic issues that need to be improved to better serve people from under-resourced neighborhoods.”

    A limitation of the study was that researchers did not have information on other factors that could affect stroke treatment, such as the time symptoms started or how severe the stroke was.

    The study was supported by ICES, a health research institute in Ontario; the Heart and Stroke Foundation of Canada; PSI Foundation; and Ontario Health Data Platform.

    Learn more about stroke at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.

    When posting to social media channels about this research, we encourage you to use the hashtags #Neurology and #AANscience.

    The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 40,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

    For more information about the American Academy of Neurology, visit AAN.com or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube.

    [ad_2]

    American Academy of Neurology (AAN)

    Source link

  • Scientists reveal structures of neurotransmitter transporter

    Scientists reveal structures of neurotransmitter transporter

    [ad_1]

    Newswise — (Memphis, Tenn – November 1, 2023) Neurons talk to each other using chemical signals called neurotransmitters. Scientists at St. Jude Children’s Research Hospital have drawn on structural biology expertise to determine structures of vesicular monoamine transporter 2 (VMAT2), a key component of neuronal communication. By visualizing VMAT2 in different states, scientists now better understand how it functions and how the different shapes the protein takes influence drug binding — critical information for drug development to treat hyperkinetic (excess movement) disorders such as Tourette syndrome. The work was published today in Nature.    

    How our neurons talk to each other 

    Chemical compounds called monoamines, which include dopamine, serotonin and adrenaline, play a central role in neuronal communication. These molecules affect how the brain works, controlling our emotions, sleep, movement, breathing, circulation and many other functions. Monoamines are neurotransmitters (signaling molecules) produced and released by neurons, but before they can be released, they must first be packaged into vesicles.  

    Vesicles are cellular compartments that store neurotransmitters before they are released at the synapses (the junction through which chemical signals pass from one neuron to another). Think of vesicles as the cargo ships of the neuronal cell — neurochemicals are packed inside them and taken to where they need to go. VMATs are proteins on the membrane of these vesicles that move monoamines into the space within, acting like loading cranes for the cargo ships.  

    “VMATs are transporters that are required for packing these monoamine neurotransmitters into synaptic vesicles,” explained co-corresponding author Chia-Hsueh Lee, Ph.D., St. Jude Department of Structural Biology.   

    Once the VMAT has packed the vesicle with monoamines, the “cargo ship” moves towards the synaptic gap (the space between neurons), where it releases the chemical compounds.  

    The many faces of monoamine transporters 

    There are two types of VMAT: VMAT1 and VMAT2. VMAT1 is more specialized, found only in neuroendocrine cells, whereas VMAT2 is found throughout the neuronal system and has significant clinical relevance.   

    “We knew that VMAT2 is physiologically very important,” Lee said. “This transporter is a target for pharmacologically relevant drugs used in the treatment of hyperkinetic disorders such as chorea and Tourette Syndrome.” 

    Despite their importance, the structure of VMAT2, which would allow researchers to investigate how it works fully, had remained elusive. Lee and his team used cryo-electron microscopy (cryo-EM) to obtain structures of VMAT2 bound to the monoamine serotonin and the drugs tetrabenazine and reserpine, which are used to treat chorea and hypertension, respectively. This was no easy feat.  

    “VMAT2 is a small membrane protein,” explained co-first author Yaxin Dai, PhD., St. Jude Department of Structural Biology. “This makes it a very challenging target for cryo-EM structure determination.”  

    Despite the difficulty and using some clever tricks, the team captured multiple structures of VMAT2 that allowed them to tease out how the protein functions and investigate how exactly those drugs work. “VMAT transporters adopt multiple conformations [shapes] while transporting their substrate. This is called alternating access transport, where the protein is either “outward” or “inward” facing,” explained co-first author Shabareesh Pidathala, Ph.D., St. Jude Department of Structural Biology. “To completely gain mechanistic understanding at an atomic level, we needed to capture multiple conformations of this transporter.”  

    Answering a 40-year-old question 

    The researchers discovered this dynamic mechanism means multiple opportunities for drugs to bind. They confirmed that reserpine and tetrabenazine bind two different conformations of VMAT2. “30 or 40 years of pharmacological research had suggested that these two drugs bind to the transporter in different ways,” said Pidathala, “but nobody knew the atomic details of how this works. Our structures nicely demonstrate that these two drugs stabilize two different conformations of the transporter to block its activity.” 

    The structure of VMAT2 with serotonin bound allowed the researchers to pinpoint specific amino acids that interact with the neurotransmitter and drive transport. “We believe this is a common mechanism that this transporter uses to engage all the monoamines,” said Lee.  

    While this work offers a huge leap forward in understanding monoamine transport, Lee and his team are delving deeper into its mechanism. For example, the intake of monoamines into vesicles is fueled by protons moving in the other direction. “We identified amino acids that are important for this proton-dependent process,” Lee said, “but we still don’t know how exactly protons drive this transport. Determining this mechanism is our future direction, which will help us to fully appreciate how this transporter works.”  

    Authors and funding 

    The study’s other first author is Shuyun Liao of the School of Life Sciences, Peking University. The study’s co-corresponding author is Zhe Zhang of the School of Life Sciences, Peking University. Other authors include Xiao Li and Chi-Lun Chang of St. Jude, and Changkun Long of the School of Life Sciences, Peking University.  

    The study was supported by grants from National Institutes of Health (R01GM143282), the National Key Research and Development Program of China (2021YFA1302300), the National Natural Science Foundation of China (32171201), the SLS-Qidong innovation fund, the Li Ge-Zhao Ning Life Science Youth Research Foundation, the State Key Laboratory of Membrane Biology of China, and ALSAC, the fundraising and awareness organization of St. Jude. 

     

    St. Jude Children’s Research Hospital  

    St. Jude Children’s Research Hospital is leading the way the world understands, treats and cures childhood cancer, sickle cell disease and other life-threatening disorders. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude shares the breakthroughs it makes to help doctors and researchers at local hospitals and cancer centers around the world improve the quality of treatment and care for even more children. To learn more, visit stjude.org, read St. Jude Progress blog, and follow St. Jude on social media at @stjuderesearch.   

    [ad_2]

    St. Jude Children’s Research Hospital

    Source link

  • fMRI study finds correlated shifts in brain connectivity associated with overthinking in adolescents

    fMRI study finds correlated shifts in brain connectivity associated with overthinking in adolescents

    [ad_1]

    Newswise — COLUMBUS, Ohio – A new study from The Ohio State University Wexner Medical Center and College of Medicine, University of Utah and University of Exeter (UK) substantiates previous groundbreaking research that rumination (overthinking) can be reduced through an intervention called Rumination-focused Cognitive Behavioral Therapy (RF-CBT). In addition, the use of fMRI technology allowed researchers to observe correlated shifts in the brain connectivity associated with overthinking.

    Study findings are published online in the journal Biological Psychiatry Global Open Science.

    “We know adolescent development is pivotal. Their brains are maturing, and habits are forming. Interventions like RF-CBT can be game-changers, steering them towards a mentally healthy adulthood. We were particularly excited that the treatment seemed developmentally appropriate and was acceptable and accessible via telehealth during the early pandemic,” said corresponding author Scott Langenecker, PhD, vice chair of research in the Department of Psychiatry and Behavioral Health at Ohio State, who started this project while at the University of Utah.

    RF-CBT is a promising approach pioneered by Ed Watkins, PhD, professor of experimental and applied Clinical Psychology at the University of Exeter. It has been shown to be effective among adults with recurrent depression.

    “We wanted to see if we could adapt it for a younger population to prevent the ongoing burden of depressive relapse,” said Rachel Jacobs, PhD, adjunct assistant professor of psychiatry and behavioral sciences at Northwestern University who conducted the pilot study in 2016.

    “As a clinician, I continued to observe that standard CBT tools such as cognitive restructuring didn’t give young people the tools to break out of the painful mental loops that contribute to experiencing depression again. If we could find a way to do that, maybe we could help young people stay well as they transition to adulthood, which has become even more important since we’ve observed the mental health impact of COVID-19,” Jacobs said.

    In the just published trial, 76 teenagers, ages 14-17, with a history of depression were randomly assigned to 10-14 sessions of RF-CBT, while controls were allowed and encouraged to receive any standard treatment. Teens reported ruminating significantly less if they received RF-CBT. Even more intriguing, fMRI illustrated shifts in brain connectivity, marking a change at the neural level.

    Specifically, there was a reduction in the connection between the left posterior cingulate cortex and two other regions; the right inferior frontal gyrus and right inferior temporal gyrus. These zones, involved in self-referential thinking and emotional stimuli processing, respectively, suggest RF-CBT can enhance the brain’s ability to shift out of the rumination habit. Notably, this work is a pre-registered replication; it demonstrates the same brain and clinical effects in the Utah sample in 2023 that was first reported in the Chicago sample in 2016.

    “For the first time, this paper shows that the version of rumination-focused CBT we have developed at the University of Exeter leads to changes in connectivity in brain regions in adolescents with a history of depression relative to treatment as usual. This is exciting, as it suggests the CBT either helps patients to gain more effortless control over rumination or makes it less habitual. We urgently need new ways to reduce rumination in this group in order to improve the mental health of our young people,” Watkins said.

    Next, the researchers will focus on demonstrating the efficacy of RF-CBT in a larger sample with an active treatment control, including continued work at Ohio State, Nationwide Children’s Hospital, University of Exeter, University of Utah and the Utah Center for Evidence Based Treatment. Future directions include bolstering access to teens in clinical settings and enhancing the ways we can learn about how this treatment helps youth with similar conditions.

    “Our paper suggests a science-backed method to break the rumination cycle and reinforces the idea that it’s never too late or too early to foster healthier mental habits. Our research team thanks the youths and families who participated in this study for their commitment and dedication to reducing the burden of depression through science and treatment, particularly during the challenges of a global pandemic,” Langenecker said.

    This work was supported by the National Institutes of Mental Health and funds from the Huntsman Mental Health Institute and is dedicated to researcher Kortni K. Meyers and others who have lost their lives to depression.

     # # #

    [ad_2]

    Ohio State University Wexner Medical Center

    Source link

  • Underwater robot finds new circulation pattern in Antarctic ice shelf

    Underwater robot finds new circulation pattern in Antarctic ice shelf

    [ad_1]

    Newswise — ITHACA, N.Y. – More than merely cracks in the ice, crevasses play an important role in circulating seawater beneath Antarctic ice shelves, potentially influencing their stability, finds Cornell University-led research based on a first-of-its-kind exploration by an underwater robot.

    The remotely operated Icefin robot’s climb up and down a crevasse in the base of the Ross Ice Shelf produced the first 3D measurements of ocean conditions near where it meets the coastline, a critical juncture known as the grounding zone.

    The robotic survey revealed a new circulation pattern – a jet funneling water sideways through the crevasse – in addition to rising and sinking currents, and diverse ice formations shaped by shifting flows and temperatures. Those details will improve modeling of ice shelf melting and freezing rates at grounding zones, where few direct observations exist, and of their potential contribution to global sea-level rise.

    “Crevasses move water along the coastline of an ice shelf to an extent previously unknown, and in a way models did not predict,” said Peter Washam, a polar oceanographer and research scientist at Cornell University. “The ocean takes advantage of these features, and you can ventilate the ice shelf cavity through them.”

    Washam is the lead author of “Direct Observations of Melting, Freezing and Ocean Circulation in an Ice Shelf Basal Crevasse,” published in Science Advances.

    The scientists in late 2019 deployed the Icefin vehicle – roughly 12 feet long and less than 10 inches around – on a tether down a 1,900-foot borehole drilled with hot water, near where Antarctica’s largest ice shelf meets the Kamb Ice Stream. Such so-called grounding zones are key to controlling the balance of ice sheets, and the places where changing ocean conditions can have the most impact.

    On the team’s last of three dives, Matthew Meister, a senior research engineer, drove Icefin into one of five crevasses found near the borehole. Equipped with thrusters, cameras, sonar and sensors for measuring water temperature, pressure and salinity, the vehicle climbed nearly 150 feet up one slope and descended the other.

    The survey detailed changing ice patterns as the crevasse narrowed, with scalloped indentations giving way to vertical runnels, then green-tinted marine ice and stalactites. Melting at the crevasse base and salt rejection from freezing near the top moved water up and down around the horizontal jet, driving uneven melting and freezing on the two sides, with more melting along the lower downstream wall.

    “Each feature reveals a different type of circulation or relationship of the ocean temperature to freezing,” Washam said. “Seeing so many different features within a crevasse, so many changes in the circulation, was surprising.”

    The researchers said the findings highlight crevasses’ potential to transport changing ocean conditions – warmer or colder – through an ice shelf’s most vulnerable region.

    “If water heats up or cools off, it can move around in the back of the ice shelf quite vigorously, and crevasses are one of the means by which that happens,” Washam said. “When it comes to projecting sea-level rise, that’s important to have in the models.”

    The research was funded by Project RISE UP (Ross Ice Shelf and Europa Underwater Probe), part of NASA’s Planetary Science and Technology from Analog Research program, with logistical support provided by the National Science Foundation through the U.S. Antarctic Program. It was facilitated by the New Zealand Antarctic Research Institute, Aotearoa New Zealand Antarctic Science Platform and the Victoria University of Wellington Hot Water Drilling initiative.

    [ad_2]

    Cornell University

    Source link

  • Find-and-Replace Genome Editing with CRISPR: A Promising Therapeutic Strategy

    Find-and-Replace Genome Editing with CRISPR: A Promising Therapeutic Strategy

    [ad_1]

    Newswise — Severe Combined Immunodeficiencies (SCIDs) are a group of debilitating primary immunodeficiency disorders, primarily caused by genetic mutations that disrupt T-cell development. SCID can also affect B-cell and natural killer cell function and counts. Left untreated, SCID proves fatal within the first year of life. The conventional treatment for SCID patients involves allogeneic hematopoietic stem cell transplantation (HSCT), but the challenges of finding compatible donors and potential complications like graft-versus-host disease (GVHD) pose significant hurdles in this approach.

    A groundbreaking solution has emerged with the advent of genome editing (GE), particularly using CRISPR-Cas9 technology. This cutting-edge gene therapy research offers hope for many genetic disorders such as SCID. The CRISPR-Cas9 system creates site-specific double-strand breaks in the DNA, allowing for precise gene editing. The repair process can either disrupt a specific gene or correct it, potentially targeting nearly any gene in the genome. This development opens the door to therapeutic interventions for a wide range of genomic diseases.

    One promising genome-editing approach, CRISPR-Cas9 Homology-directed repair (HDR)-mediated GE, offers the potential for precise gene insertion. In certain subtypes of SCID, an alternative to HSCT can involve conventional CRISPR-Cas9 HDR-mediated gene insertion, but it carries inherent risks, especially in cases like RAG2-SCID. RAG2 is nuclease involved in DNA cleavage during lymphocyte development, and CRISPR-Cas9 HDR-mediated gene insertion may lead to uncontrolled RAG2 nuclease activity and harmful structural variations.

    In response, researchers from Bar-Ilan University in Israel propose a novel replacement strategy, termed GE x HDR 2.0: Find and Replace. This approach, outlined in a paper published today in Nature Communications, combines CRISPR-Cas9-mediated genome editing with recombinant adeno-associated serotype 6 (rAAV6) DNA donor vectors to precisely replace the RAG2 coding sequence while preserving regulatory elements. This strategy can be applied also to other genes with hot spot regions for disease-causing mutations.

    Dr. Ayal Hendel, of Bar-Ilan University’s Goodman Faculty of Life Sciences, emphasized, “Our innovation hinges on a crucial insight: to efficiently trigger CRISPR-Cas9 HDR-mediated GE for precise coding sequence replacement, it’s essential to separate the distal homology arm from the cleavage site and align it with the sequence immediately downstream of the segment needing replacement. In this process, elongating the distal homology arm length in the donor is of paramount importance. By preserving endogenous regulatory elements and intronic sequences, our approach faithfully reproduces natural gene expression levels, thus reducing the associated risks of unregulated gene expression. This groundbreaking technique, which involves replacing entire coding sequences or exons while retaining critical regulatory elements, brings hope to patients with RAG2-SCID and holds promise for the treatment of various other genetic disorders.”

    [ad_2]

    Bar-Ilan University

    Source link

  • How mosquito-controlling bacteria might also enhance insect fertility

    How mosquito-controlling bacteria might also enhance insect fertility

    [ad_1]

    Newswise — A new study reveals biological mechanisms by which a specific strain of bacteria in the Wolbachia genus might enhance the fertility of the insects it infects—with potentially important implications for mosquito-control strategies. Shelbi Russell of the University of California Santa Cruz, US, and colleagues report these findings in the open access journal PLOS Biology on October 24th.

    Different strains of Wolbachia bacteria naturally infect a number of different animals worldwide, such as mosquitos, butterflies, and fruit flies. Wolbachia can manipulate the fertility of their hosts through a specific biological mechanism that aids the spread of Wolbachia within host populations. In recent years, people have harnessed that mechanism in strategies to deliberately infect mosquitos with a specific Wolbachia strain, reducing targeted mosquito populations and thereby potentially reducing the spread of human viruses carried by mosquitos, such as dengue or Zika.

    Research in fruit flies suggests that that same strain, which is native to fruit flies, may also enhance insect fertility, with potentially important implications for mosquito control. Evidence suggests that biological processes involving the fruit-fly protein meiotic-P26 (“mei-P26″), which is essential for fruit-fly reproduction, may underlie this enhanced fertility. However, these processes have remained unclear.

    To investigate, Russell and colleagues bred fruit flies with various defects affecting mei-P26—resulting in reduced fruit-fly fertility—and examined what happened when they then infected the flies with the fruit-fly-native Wolbachia strain.

    They found that Wolbachia infection restored fertility in fruit flies with various mei-P26 defects, enabling them to produce more offspring than uninfected flies. Further experiments revealed how Wolbachia may restore fertility by mitigating certain perturbing effects of mei-P26 defects on specific genes and proteins, thereby resolving problems with the stem cells that produce fruit fly eggs and sperm.

    In additional experiments, Wolbachia infection also enhanced the fertility of fruit flies without mei-P26 defects, resulting in higher egg lay and hatch rates.

    These findings help to resolve the mystery of how this particular Wolbachia strain enhances fruit-fly fertility. Further research will be needed to better understand these effects and their potential implications for strategies that employ this strain to control mosquito populations.

    Russell adds, “Wolbachia endosymbionts exist at high infection frequencies in many host populations, despite exhibiting weak gene drive systems and unobserved impacts on host fitness. Here, we show that the wMel strain of Wolbachia is able to rescue and reinforce host fertility, demonstrating their capacity to function as a beneficial symbiont.”

    #####

    In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002335

    Press-only preview: https://plos.io/3tudL1r

     

    Image Caption: A mei-P26 mutant Drosophila melanogaster ovariole infected with wMel bacterial symbionts. DNA is stained in red, anti-Vasa protein is stained blue, and anti-Hu-li tai shao ring canal protein is stained cyan.

    Image Credit: Shelbi Russell (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)

    Image URL: https://plos.io/459VWBV

    Citation: Russell SL, Castillo JR, Sullivan WT (2023) Wolbachia endosymbionts manipulate the self-renewal and differentiation of germline stem cells to reinforce fertility of their fruit fly host. PLoS Biol 21(10): e3002335. https://doi.org/10.1371/journal.pbio.3002335

    Author Countries: United States

    Funding: This work was supported by the UC Santa Cruz Chancellor’s Postdoctoral Fellowship and the NIH (R00GM135583 to SLR; R35GM139595 to WTS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Competing interests: The authors have declared that no competing interests exist.

    [ad_2]

    PLOS

    Source link

  • ESMO: Pre- and post-surgical immunotherapy improves outcomes for patients with operable lung cancer

    ESMO: Pre- and post-surgical immunotherapy improves outcomes for patients with operable lung cancer

    [ad_1]

    Newswise — MADRID ― Compared with pre-surgical (neoadjuvant) chemotherapy alone, adding perioperative immunotherapy – given before and after surgery – significantly improved event-free survival (EFS) in patients with resectable early-stage non-small cell lung cancer (NSCLC). Results from the Phase III CheckMate 77T study were presented today at the 2023 European Society for Medical Oncology (ESMO) Congress by researchers from The University of Texas MD Anderson Cancer Center.

    At a median follow-up of 25.4 months, the median EFS with chemotherapy alone was 18.4 months, while the median had not yet been reached for patients receiving perioperative nivolumab, meaning EFS was prolonged significantly over the control group. These results correspond to a 42% reduction in risk of disease progression, recurrence, or death for those receiving the perioperative combination.

    Patients who received the perioperative nivolumab-based regimen also saw significantly higher rates of pathological complete response (pCR), defined as no tumor remaining at surgery, compared with those who received chemotherapy alone (25.3% vs. 4.7%). Rates of major pathological response (MPR), less than or equal to 10% of viable tumor cells remaining at time of surgery, were also higher in patients who received perioperative immunotherapy (35.4% vs. 12.1%).

    “This study builds on the standard-of-care neoadjuvant treatment and supports perioperative nivolumab as an effective approach that reduces the risk of lung cancer relapse,” said principal investigator Tina Cascone, M.D., Ph.D., associate professor of Thoracic/Head & Neck Medical Oncology. “These findings add to evidence that the perioperative immunotherapy path gives patients with operable lung cancer an opportunity to live longer without their cancer returning.”

    Roughly 30% of patients diagnosed with NSCLC have operable disease, meaning their tumor can be removed by a surgical operation. While many of these patients can be potentially cured by surgery, more than half will experience cancer recurrence without additional therapy. Chemotherapy given either before or after surgery provides only a minimal survival benefit.

    The randomized, double-blind CheckMate 77T trial, which began in 2019, included more than 450 NSCLC patients over the age of 18 from around the globe. Participants were randomized to treatment with either neoadjuvant nivolumab with chemotherapy followed by surgery and adjuvant nivolumab, or neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo

    The data showed no new safety signals with the perioperative nivolumab regimen and is consistent with the known safety profiles of individual agents. Grade 3-4 treatment-related side effects were observed in 32% and 25% of patients receiving the perioperative combination or control therapy, respectively. Surgery-related adverse events occurred in 12% of patients in both treatment arms.

    These findings add to recent success seen with neoadjuvant nivolumab plus chemotherapy in NSCLC. In March 2022, the Phase III CheckMate 816 study led to FDA approval of nivolumab combined with platinum-based chemotherapy.

    “I am enthusiastic about the initial findings of the study,” Cascone said. “Looking ahead, it will be critical to identify patient and disease characteristics that will tell us who can potentially be cured with neoadjuvant immunotherapy only and who will benefit from more intensified treatment strategies.”

    The CheckMate 77T study was sponsored by Bristol Myers Squibb. A full list of co-authors and author disclosures can be found here.

    Read this press release on the MD Anderson Newsroom. 

    [ad_2]

    University of Texas MD Anderson Cancer Center

    Source link

  • Kidney cancer study shows improved outcomes for patients with advanced disease when treated with belzutifan over everolimus

    Kidney cancer study shows improved outcomes for patients with advanced disease when treated with belzutifan over everolimus

    [ad_1]

    Newswise — Boston – Belzutifan significantly reduced the risk of progression of clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, in patients previously treated with immune checkpoint inhibitors and anti-angiogenic therapies compared with everolimus in a phase 3 clinical trial. The trial, led by Toni K. Choueiri, MD, Director of the Lank Center for Genitourinary Cancer at Dana-Farber Cancer Institute, showed the risk of progression was reduced by 25-26%.

    The results were presented at the annual European Society for Medical Oncology (ESMO) Congress on October 21, 2023, in Madrid, Spain.

    “This is real progress for patients and could lead to approval of this drug for this patient group,” says Choueiri, senior author on the presentation in Madrid.

    Belzutifan, a HIF-2α inhibitor, is currently approved for patients with Von Hippel-Landau (VHL) disease-associated renal cell carcinoma, a form of kidney cancer. The drug was originally investigated and approved for kidney cancer patients with VHL disease because they have inherited a mutation that inactivates the VHL gene, which results in an overabundance of HIF-2α in cells.

    When overabundant in cells, HIF-2α is associated with increased cancer-driving activity, such as cell proliferation, immune evasion, low oxygen levels (called hypoxia), and blood vessel formation (called angiogenesis). Dana-Farber’s William G. Kaelin, Jr., MD, was awarded a Nobel Prize in Physiology or Medicine in 2019 for the discovery of the role HIF-2α in cancer and other diseases.

    “The knowledge we have about hypoxia and angiogenesis in kidney cancer stemmed from this essential pre-clinical research at Dana-Farber,” says Choueiri. “Bringing this knowledge forward to benefit patients is very gratifying.”

    While the mutation that causes VHL disease is inherited, spontaneous mutations that inactivate VHL occur in over 90% of ccRCC tumors, suggesting that a HIF-2α inhibitor might also benefit patients with ccRCC.

    This trial, called LITESPARK-005, enrolled 746 patients with metastatic ccRCC who had progressed after treatment with both an immune checkpoint inhibitor (ICI), such as a PD-1 or PD-L1 inhibitor, and an anti-angiogenic therapy. ICIs and anti-angiogenic medicines have become a standard part of first- and second-line therapies for metastatic ccRCC, though most patients eventually experience disease progression and need additional treatment options.

    Patients were randomized to receive treatment with either belzutifan or everolimus. At the second interim analysis, after a median of 25.7 months, patients taking belzutifan were 26% less likely to have progressed compared with those taking everolimus.

    The overall response rate was also higher with belzutifan, at 22% versus 3.5%, and 13 patients experienced a complete response with belzutifan compared to none with everolimus. Patients taking belzutifan were also less likely to discontinue therapy due to side effects.

    “Importantly, quality of life favored belzutifan,” says Choueiri.

    There was an improvement in overall survival with belzutifan though it was not statistically significant.

    This investigation of monotherapy with belzutifan is part of a broader strategy to learn more about the efficacy and safety of HIF-2α inhibition in RCC. The strategy involves multiple LITESPARK trials examining beluzutifan alone and in combination with other therapies in treatment-naive and pre-treated disease settings. Choueiri also presented updated findings from the phase 2 LITESPARK-003 at the ESMO Congress that showed belzutifan plus cabozantinib showed durable antitumor activity and a safety profile consistent with prior observation previously published in The Lancet Oncology.

    Both trials are sponsored by Merck Sharp & Dohme LLC.

    ESMO Session Details

    LBA 87: Phase 2 LITESPARK-003 Study of belzutifan in combination with cabozantinib for advanced clear cell renal cell carcinoma (ccRCC) will be presented in Proffered Paper Session 2 – Genitourinary tumors, non-prostate on Saturday, October 21, 2023, at 8:45am ET (14:45 CEST) Toni K. Choueiri, MD/First Author

    LBA 88: Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): randomized open-label phase 3 LITESPARK-005 study will be presented in Proffered Paper Session 2- Genitourinary tumors, non-prostate on Saturday, October 21, 2023, at 8:55am ET (14:55 CEST) Toni K. Choueiri, MD/Senior Author

    About Dana-Farber Cancer Institute 

    Dana-Farber Cancer Institute is one of the world’s leading centers of cancer research and treatment. Dana-Farber’s mission is to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber is a federally designated Comprehensive Cancer Center and a teaching affiliate of Harvard Medical School.

    We provide the latest treatments in cancer for adults through Dana-Farber Brigham Cancer Center and for children through Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dana-Farber is the only hospital nationwide with a top 5 U.S. News & World Report Best Cancer Hospital ranking in both adult and pediatric care.

    ###

    [ad_2]

    Dana-Farber Cancer Institute

    Source link

  • Superlensing without a super lens: physicists boost microscopes beyond limits

    Superlensing without a super lens: physicists boost microscopes beyond limits

    [ad_1]

    Newswise — Ever since Antonie van Leeuwenhoek discovered the world of bacteria through a microscope in the late seventeenth century, humans have tried to look deeper into the world of the infinitesimally small.

    There are, however, physical limits to how closely we can examine an object using traditional optical methods. This is known as the ‘diffraction limit’ and is determined by the fact that light manifests as a wave. It means a focused image can never be smaller than half the wavelength of light used to observe an object.

    Attempts to break this limit with “super lenses” have all hit the hurdle of extreme visual losses, making the lenses opaque. Now physicists at the University of Sydney have shown a new pathway to achieve superlensing with minimal losses, breaking through the diffraction limit by a factor of nearly four times. The key to their success was to remove the super lens altogether. 

    The research is published today in Nature Communications.

    The work should allow scientists to further improve super-resolution microscopy, the researchers say. It could advance imaging in fields as varied as cancer diagnostics, medical imaging, or archaeology and forensics. 

    Lead author of the research, Dr Alessandro Tuniz from the School of Physics and University of Sydney Nano Institute, said: “We have now developed a practical way to implement superlensing, without a super lens. 

    “To do this, we placed our light probe far away from the object and collected both high- and low-resolution information. By measuring further away, the probe doesn’t interfere with the high-resolution data, a feature of previous methods.” 

    Previous attempts have tried to make super lenses using novel materials. However, most materials absorb too much light to make the super lens useful.

    Dr Tuniz said: “We overcome this by performing the superlens operation as a post-processing step on a computer, after the measurement itself. This produces a ‘truthful’ image of the object through the selective amplification of evanescent, or vanishing, light waves. 

    Co-author, Associate Professor Boris Kuhlmey, also from the School of Physics and Sydney Nano, said: “Our method could be applied to determine moisture content in leaves with greater resolution, or be useful in advanced microfabrication techniques, such as non-destructive assessment of microchip integrity.

    “And the method could even be used to reveal hidden layers in artwork, perhaps proving useful in uncovering art forgery or hidden works.”

    Typically, superlensing attempts have tried to home in closely on the high-resolution information. That is because this useful data decays exponentially with distance and is quickly overwhelmed by low-resolution data, which doesn’t decay so quickly. However, moving the probe so close to an object distorts the image.

    “By moving our probe further away we can maintain the integrity of the high-resolution information and use a post-observation technique to filter out the low-resolution data,” Associate Professor Kuhlmey said.

    The research was done using light at terahertz frequency at millimetre wavelength, in the region of the spectrum between visible and microwave.

    Associate Professor Kuhlmey said: “This is a very difficult frequency range to work with, but a very interesting one, because at this range we could obtain important information about biological samples, such as protein structure, hydration dynamics, or for use in cancer imaging.”

    Dr Tuniz said: “This technique is a first step in allowing high-resolution images while staying at a safe distance from the object without distorting what you see.

    “Our technique could be used at other frequency ranges. We expect anyone performing high-resolution optical microscopy will find this technique of interest.”

    DOWNLOAD images at this link.

     

     

     Research paper: A Tuniz & B Kuhlmey, ‘Subwavelength terahertz imaging via virtual superlensing in the radiating near field’, Nature Communications (2023)

    DOI: 10.1038/s41467-023-41949-5

    (Available on request)

     

    DECLARATION

     

    The authors declare no competing financial interests. Research was in part funded by the Australian Research Council.

     

     

    [ad_2]

    University of Sydney

    Source link

  • Opioid use disorder treatment associated with decreased risk of overdose after surgery, suggests first-of-its-kind study of over 4 million surgeries

    Opioid use disorder treatment associated with decreased risk of overdose after surgery, suggests first-of-its-kind study of over 4 million surgeries

    [ad_1]

    Newswise — SAN FRANCISCO — Although people with opioid use disorder (OUD) are significantly more likely to overdose or have a complication after major surgery than those without the disorder, using medications for the treatment of OUD before surgery may eliminate that extra risk, suggests a large, first-of-its-kind study presented at the ANESTHESIOLOGY® 2023 annual meeting.

    Patients with OUD who didn’t use an OUD medication (such as buprenorphine or methadone) were over four times more likely to overdose after having surgery, yet those who used evidence-based OUD medication before surgery were essentially at no greater risk than those who didn’t have OUD, according to the study. Taken orally, OUD medications reduce withdrawal and cravings and prevent opioids from producing the feeling of euphoria that drives addiction.

    “We know that OUD treatments are very effective in helping to prevent relapse, overdose and death in nonsurgical patients, but our research is the first to show that they also may be remarkably effective in at-risk patients facing surgical stress and recovery pain that often is addressed with opioids,” said Anjali Dixit, M.D., MPH, a pediatric anesthesiologist at Stanford University, California. “This is helping us learn more about how to optimally treat OUD patients so that their surgical and post-surgical pain is well-controlled, while also making sure we are minimizing their risk of relapse and overdose.”

    Researchers analyzed 4,030,032 surgeries performed between 2008 and 2020 from the Merative MarketScan Commercial Database, a nationwide sample of data from patients with both employer-sponsored and Medicare Advantage insurance. The analysis reviewed overdoses and other complications (such as OUD-related hospitalization or infection) that occurred in the three months after surgery for the 25 most common surgeries, including knee and hip replacement, hysterectomy and gallbladder removal.

    Of the over 4 million surgeries, 26,827 were performed on patients who had a history of OUD, 9,699 (36%) of whom used OUD medications in the month before surgery and 17,128 (64%) who did not. OUD patients who did not use OUD medications were 4.2 times more likely to overdose or have an OUD-related infection or hospitalization than those who did not have the disorder, according to the study. OUD patients who used OUD medications did not experience a statistically different risk of opioid-related adverse events compared to those who did not have the disorder.

    As many as 7.6 million people in the U.S. live with OUD, according to research, and that number continues to grow. Only 20% of people with OUD currently use OUD medications, said Dr. Dixit. She noted the number of people in the study who used OUD medications was likely higher, because they had access to commercial insurance and therefore, better access to care. The researchers also want to look at other populations such as those on Medicaid, because they may be sicker and have less access to care.

    “The national efforts to increase access to OUD medications is good news for people with OUD, including those who need surgery,” said Dr. Dixit. “The next step is to determine if a particular medication or regimen is better than another.”

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • Black and Hispanic patients much more likely to die after surgery than white patients

    Black and Hispanic patients much more likely to die after surgery than white patients

    [ad_1]

     

    Newswise — SAN FRANCISCO — About 12,000 Black and Hispanic patients who died after surgery the past two decades may have lived if there were no racial and ethnic disparities among Americans having surgery, suggests a study of more than 1.5 million inpatient procedures presented at the ANESTHESIOLOGY® 2023 annual meeting. This estimate draws attention to the human toll of disparities in surgical outcomes, with Black patients being 42% more likely and Hispanic patients 21% more likely to die after surgery compared to white patients.

    Unless efforts to narrow the racial and ethnic gap in surgical outcomes intensify, preventable deaths will continue among minority patients, the researchers said. The development of equity policies to address disparity gaps can make a difference, with even a 2% reduction in projected excess mortality rates among Black patients averting roughly 3,000 post-surgery deaths in the next decade, they determined.

    “This study represents the first effort to move beyond merely documenting the ongoing disparities in surgical outcomes in the U.S. by quantifying the aggregate human toll of these disparities,” said Christian Mpody, M.D., Ph.D., MBA, lead author of the study and assistant professor of anesthesiology and pediatrics at The Ohio State University College of Medicine, Columbus. “We should not become used to reading statistics about people dying. It’s essential to remember that beyond the statistics, odds ratios and p-values, these are real people — brothers, sisters, mothers and fathers.”

    “The findings bring to light the deaths that may have been preventable if people of various racial and ethnic backgrounds had comparable mortality rates to white patients,” he said. “That’s important for conveying the gravity of the issue to policymakers, health care professionals and the general public.”

    Researchers analyzed the Nationwide Inpatient Sample data of more than a million surgical procedures performed at 7,740 U.S. hospitals between 2000 and 2020. They determined Black patients were 42% more likely than white patients to die within 30 days of surgery, driven by higher mortality in the Northeast (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island and Vermont). Hispanic patients were 21% more likely than white patients to die within 30 days of surgery, driven by higher mortality in the West (Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington and Wyoming). 

    Although death rates declined for all groups over the 20-year period, the disparity gaps did not narrow over time. The study did not identify causes of death.

    “It’s important to note that disparities in these regions do not necessarily mean that the surgical care is inferior. It may reflect overall population health and socioeconomic conditions,” said Dr. Mpody. “Our team is currently investigating the underlying causes of these regional variations.”

    Dr. Mpody said the study didn’t assess the effectiveness of specific interventions or policies, noting that addressing the problem requires a three-pronged approach involving research, education and service. Suggested interventions by the authors include increasing investment in disparity research and incorporating race and racism lectures in medical and nursing school curricula. Health systems should: provide cultural competency training; focus on diversity in grand rounds; invest in patient education and health literacy; develop personalized medicine approaches that take into account individual patients’ needs and race-sensitive protocols; and increase the number of minority providers. 

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

     

    # # #

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • Anesthesiologist-led blood management programs save hospitals significant amounts of blood and reduce costs with same or better patient outcomes

    Anesthesiologist-led blood management programs save hospitals significant amounts of blood and reduce costs with same or better patient outcomes

    [ad_1]

     

    Newswise — SAN FRANCISCO — Blood management programs that reduced or avoided transfusions saved a health system millions of dollars annually, with a return on investment of more than $7 for every dollar spent, while achieving the same or better outcomes, suggests research presented at the ANESTHESIOLOGY® 2023 annual meeting. 

    Over the past 10 years, the Johns Hopkins Health System established a comprehensive blood management program with two primary goals: 1) to reduce unnecessary transfusions across the five-hospital health system, and 2) to provide specialized care that avoids transfusions in patients who decline them. Together these efforts save blood and reduce costs, making more blood available for those who really need it, such as trauma patients. Transfusions are routinely used for emergencies and trauma, but also are needed in heart, transplant, hip or knee replacement, spine, vascular, liver and pancreatic surgery. Nonsurgical patients also need blood, for example those with cancer (leukemia, lymphoma), sickle cell anemia or gastrointestinal bleeding.

    “Since we are always dealing with blood shortages, doing more with less is critically important,” said Steven M. Frank, M.D., lead author of the study and professor in the Department of Anesthesiology and Critical Care Medicine at Johns Hopkins Medicine, Baltimore. “We like to say that blood saves lives when you need it, but only increases risks and costs when you don’t. Our results showed that a comprehensive blood management program can substantially help the bottom line — for every dollar spent, we received $7.50 in return.”

    Starting in 2012, two anesthesiologist-led, multidisciplinary blood management programs were run side by side. 

    • The Patient Blood Management Clinical Community program was designed to reduce unnecessary transfusions using several methods. The methods include evidence-based transfusion triggers, a “Why Give 2 When 1 Will Do?” single unit of blood transfusion campaign, and other anesthesiology-led before, during or after surgery measures of “keeping blood in the patient” such as using medications or intentionally lowering blood pressure to reduce bleeding and using smaller tubes to collect blood for lab tests. Over a 10-year period, the annual blood acquisition cost reduction was $2.9 million, a 10.9% decrease and a 9.6-fold return on investment.
    • The Center for Bloodless Medicine and Surgery program was designed to avoid transfusions entirely for those who don’t accept them, primarily Jehovah’s Witness patients. The program brings in revenue by attracting patients who are often turned down by other hospitals. Over 10 years, the program brought in approximately $5 million a year (after subtracting the direct cost of care), representing a 6.6-fold return on investment. 

    Clinical outcomes such as infection, blood clots, kidney injury, heart attack or stroke were the same before and after the Patient Blood Management Clinical Community program was instituted. Clinical outcomes were the same or better for the Center for Bloodless Medicine and Surgery program, as the incidence of hospital-acquired infection was significantly lower when transfusions were avoided. 

    “By reducing unnecessary medical procedures, we are actually doing more with less and providing higher value care,” said Dr. Frank. “Since clinical outcomes are either the same or better while giving less blood, the patients benefit from reduced risks and costs.”

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

     

    # # #

     

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • AI Pain Recognition System Could Help Detect Patients’ Pain Before, During and After Surgery

    AI Pain Recognition System Could Help Detect Patients’ Pain Before, During and After Surgery

    [ad_1]

    Newswise — SAN FRANCISCO — An automated pain recognition system using artificial intelligence (AI) holds promise as an unbiased method to detect pain in patients before, during and after surgery, according to research presented at the ANESTHESIOLOGY® 2023 annual meeting.

    Currently, subjective methods are used to assess pain, including the Visual Analog Scale (VAS) — where patients rate their own pain — and the Critical-Care Pain Observation Tool (CPOT) — where health care professionals rate the patient’s pain based on facial expression, body movement and muscle tension. The automated pain recognition system uses two forms of AI, computer vision (giving the computer “eyes”) and deep learning so it can interpret the visuals to assess patients’ pain.

    “Traditional pain assessment tools can be influenced by racial and cultural biases, potentially resulting in poor pain management and worse health outcomes,” said Timothy Heintz, B.S., lead author of the study and a fourth-year medical student at the University of California San Diego. “Further, there is a gap in perioperative care due to the absence of continuous observable methods for pain detection. Our proof-of-concept AI model could help improve patient care through real-time, unbiased pain detection.”

    Early recognition and effective treatment of pain have been shown to decrease the length of hospital stays and prevent long-term health conditions such as chronic pain, anxiety and depression.

    Researchers provided the AI model 143,293 facial images from 115 pain episodes and 159 non-pain episodes in 69 patients who had a wide range of elective surgical procedures, from knee and hip replacements to complex heart surgeries. The researchers taught the computer by presenting it with each raw facial image and telling it whether or not it represented pain, and it began to identify patterns. Using heat maps, the researchers discerned that the computer focused on facial expressions and facial muscles in certain areas of the face, particularly the eyebrows, lips and nose. Once it was provided enough examples, it used the learned knowledge to make pain predictions. The AI-automated pain recognition system aligned with CPOT results 88% of the time and with VAS 66% of the time.

    “The VAS is less accurate compared to CPOT because VAS is a subjective measurement that can be more heavily influenced by emotions and behaviors than CPOT might be,” said Heintz. “However, our models were able to predict VAS to some extent, indicating there are very subtle cues that the AI system can identify that humans cannot.”

    If the findings are validated, this technology may be an additional tool physicians could use to improve patient care. For example, cameras could be mounted on the walls and ceilings of the surgical recovery room (post-anesthesia care unit) to assess patients’ pain — even those who are unconscious — by taking 15 images per second. This also would free up nurses and health professionals — who intermittently take time to assess the patient’s pain — to focus on other areas of care. The researchers plan to continue to incorporate other variables such as movement and sound into the model.

    Concerns about privacy would need to be addressed to ensure patient images are kept private, but the system could eventually include other monitoring features, such as brain and muscle activity to assess unconscious patients, he said.

     

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook and follow ASALifeline on Twitter and use the hashtag #ANES23.

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • More Patients Go Home Instead of to Long-Term-Care Facility When Sedation for Common Procedures Is Administered or Directed by Anesthesiologist

    More Patients Go Home Instead of to Long-Term-Care Facility When Sedation for Common Procedures Is Administered or Directed by Anesthesiologist

    [ad_1]

    Newswise — SAN FRANCISCO — Patients who had common procedures performed outside of the operating room (OR) were more likely to go home instead of to a long-term care facility when they were discharged from the hospital if their sedation was administered or directed by an anesthesiologist, rather than by a physician who is not a trained anesthesiologist, according to a first-of-its-kind study presented at the ANESTHESIOLOGY® 2023 annual meeting.

    Patients who need catheters placed in a vein, angiograms (X-ray of the blood vessels), image-guided biopsies and many other procedures typically are treated in the interventional radiology (IR) suite instead of the OR and given sedation. Sedation is a type of anesthesia that relieves anxiety, controls pain and discomfort, and sometimes makes them fall asleep. One in 10 patients admitted to the hospital requires an IR procedure and many are at increased risk for complications due to health issues or having more complex procedures.

    The study was the first to directly compare the hospital discharge outcomes of patients who received sedation administered by an anesthesiologist, or by a nurse anesthetist under the direction of an anesthesiologist, to the discharge outcomes of patients whose sedation was administered or directed by a physician who was not an anesthesiologist, such as a radiologist or cardiologist. Anesthesiologists are physicians who are experts in ensuring the safety and comfort of patients undergoing surgery and other procedures and are highly trained in critical care to manage medical emergencies if there is a complication. 

    “We focused on patients undergoing IR procedures as they often have health issues such as heart disease or diabetes and some of the procedures are high risk,” said Matthias Eikermann, M.D., Ph.D., senior author of the study and chair of the department of anesthesiology at Montefiore Medical Center, Bronx, New York. “We found anesthesiologists add value to patients undergoing interventional radiology procedures. That’s especially true for complex neurovascular procedures such as angiograms for the treatment of aneurysms or the creation of an arteriovenous (AV) fistula, a connection between an artery and a vein, for people on dialysis and those that typically take longer than an hour.”

    In the study, 9,682 patients had sedation in the IR suite and 1,639 (16.93%) were discharged from the hospital to a long-term care facility (such as a nursing home) because of complications that they may be more likely to experience due to their disease. Anesthesiologists have the training to identify these complications early and address them.

    Of those who were not discharged home, 1,429 (87%) had their sedation administered or directed by a physician who was not an anesthesiologist, often with the assistance of a nurse, and 210 (13%) had their sedation administered or directed by an anesthesiologist.

    “The anesthesiologist is not just providing sedation, but life support for the patient during the entire procedure,” said Dr. Eikermann. “The difference in outcomes is because anesthesiologists are trained to identify early complications and treat them immediately. Physicians who are not anesthesiologists are not trained to do that.”

    Anesthesiologists administered or directed sedation for higher-risk patients, such as those with more health issues or who had more invasive procedures. Despite being at higher risk, the patients who received sedation administered or directed by an anesthesiologist were nearly 70% more likely to be discharged home than those whose sedation was administered or directed by a physician who was not an anesthesiologist.

    “Increasingly, high-risk patients are undergoing procedures outside of the OR,” said Vilma Joseph, M.D., MPH, FASA, co-author of the study and director of procedural sedation at Montefiore Medical Center. “The presence of physician anesthesiologists as part of the anesthesia care team model has been associated with improved outcomes.”

    “Patients should know that they can ask for an anesthesiologist if they are concerned about excessive pain, anxiety or their safety during diagnostic procedures,” said Dr. Eikermann. “Our research suggests rethinking anesthesia assignments to ensure anesthesiologists provide sedation when patients are at higher risk due to their health or are having more complex, longer or more-invasive procedures.”

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS

    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/MadeforThisMoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • American Society of Anesthesiologists honors Stanley W. Stead, M.D., MBA, FASA, with its Distinguished Service Award

    American Society of Anesthesiologists honors Stanley W. Stead, M.D., MBA, FASA, with its Distinguished Service Award

    [ad_1]

    Newswise — SAN FRANCISCO — The American Society of Anesthesiologists (ASA) today presented Stanley W. Stead, M.D., MBA, FASA, with its 2022 Distinguished Service Award in recognition of his enduring contributions to advancing patient-centered, physician-led health care, and his advocacy related to health care economics, including value-based care and equitable physician payment models. The award is the highest honor ASA bestows and is presented annually to a member who has transformed the specialty of anesthesiology.

    A nationally recognized thought leader in health care economics, information technology and quality of care, Dr. Stead served as a professor and senior hospital executive for more than three decades. He recently retired from his positions as vice chair and professor of anesthesiology and perioperative medicine at the University of California, Los Angeles (UCLA), and senior executive director of strategic planning, utilization, perioperative services, capital planning and risk management at the University of California, Davis. He also recently retired from his role as president and founder of Stead Health Group, Inc., in Los Angeles. 

    Dr. Stead served as ASA’s vice president of professional affairs from 2013-18, where he made innumerable contributions, both within the Society and to the specialty more widely. Notably, he led ASA’s efforts in advancing value-based payment and population care models, and co-developed ASA’s Perioperative Surgical Home (PSH) model of care. He received ASA’s Excellence in Government Award in 2012 and Lifetime Achievement Award in Practice Management in 2019. 

    Dr. Stead has held numerous positions in the Society. In 1993, he created ASA’s CROSSWALK®, a guide for surgery and anesthesia Current Procedural Terminology (CPT ®) codes, for which he served as author and editor for 30 years. He chaired ASA’s Committee on Economics and ASA’s Section on Professional Practice. He also served on the ASA Board of Directors, as well as the Board of Directors of the Anesthesia Quality Institute, an ASA foundation.

    “I cannot imagine a more deserving recipient of ASA’s highest honor,” said ASA President Michael W. Champeau, M.D., FAAP, FASA. “I’ve worked alongside Dr. Stead for over 30 years. The breadth and depth of his knowledge about the specialty and health care economics have made him an invaluable resource to anesthesiology and our members.”

    In addition to his commitments to ASA, Dr. Stead is a national expert on medical coding and reimbursement, having served on the American Medical Association’s (AMA) CPT Panel and Relative Value System Update Committee, and author of AMA’s 2007 and 2008 References on Physician Quality Reporting Initiative. He received the California Society of Anesthesiologists’ Distinguished Service Award in 2019. He has published more than 120 articles and delivered more than 150 lectures and presentations worldwide on a variety of health care topics. 

    Dr. Stead received a Bachelor of Science in biochemistry, Doctor of Medicine degree and a Master of Business Administration from UCLA, where he also completed his anesthesiology residency and fellowship in cardiothoracic anesthesiology. He completed his surgery internship at Cedars-Sinai Medical Center in Los Angeles.

    The Distinguished Service Award is presented annually for outstanding clinical, educational, or scientific achievement, contribution to the specialty and/or exemplary service to the Society. ASA’s House of Delegates establishes policies governing the selection of a recipient for the Distinguished Service Award.

     

    THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS
    Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific professional society with more than 56,000 members organized to advance the medical practice of anesthesiology and secure its future. ASA is committed to ensuring anesthesiologists evaluate and supervise the medical care of all patients before, during and after surgery. ASA members also lead the care of critically ill patients in intensive care units, as well as treat pain in both acute and chronic settings.

    For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about how anesthesiologists help ensure patient safety, visit asahq.org/madeforthismoment. Join the ANESTHESIOLOGY® 2023 social conversation today. Like ASA on Facebook, follow ASALifeline on Twitter and use the hashtag #ANES23.

     

    # # #

    [ad_2]

    American Society of Anesthesiologists (ASA)

    Source link

  • Researchers Capture First-Ever Afterglow of Huge Planetary Collision in Outer Space

    Researchers Capture First-Ever Afterglow of Huge Planetary Collision in Outer Space

    [ad_1]

    Newswise — The study, published today in Nature, reports the sighting of two ice giant exoplanets colliding around a sun-like star, creating a blaze of light and plumes of dust. Its findings show the bright heat afterglow and resulting dust cloud, which moved in front of the parent star dimming it over time.

    The international team of astronomers was formed after an enthusiast viewed the light curve of the star and noticed something strange. It showed the system doubled in brightness at infrared wavelengths some three years before the star started to fade in visible light.

    Co-lead author Dr Matthew Kenworthy, from Leiden University, said: “To be honest, this observation was a complete surprise to me. When we originally shared the visible light curve of this star with other astronomers, we started watching it with a network of other telescopes.

    “An astronomer on social media pointed out that the star brightened up in the infrared over a thousand days before the optical fading. I knew then this was an unusual event.”

    The network of professional and amateur astronomers studied the star intensively including monitoring changes in the star’s brightness over the next two years. The star was named ASASSN-21qj after the network of telescopes that first detected the fading of the star at visible wavelengths.

    The researchers concluded the most likely explanation is that two ice giant exoplanets collided, producing the infrared glow detected by NASA’s NEOWISE mission, which uses a space telescope to hunt for asteroids and comets.

    Co-lead author Dr Simon Lock, Research Fellow in Earth Sciences at the University of Bristol, said: “Our calculations and computer models indicate the temperature and size of the glowing material, as well as the amount of time the glow has lasted, is consistent with the collision of two ice giant exoplanets.”

    The resultant expanding debris cloud from the impact then travelled in front of the star some three years later, causing the star to dim in brightness at visible wavelengths.

    Over the next few years, the cloud of dust is expected to start smearing out along the orbit of the collision remnant, and a tell-tale scattering of light from this cloud could be detected with both ground-based telescopes and NASA’s largest telescope in space, known as JWST.

    The astronomers plan on watching closely what happens next in this system.

    Co-author Dr Zoe Leinhardt, Associate Professor of Astrophysics at the University of Bristol, added: “It will be fascinating to observe further developments. Ultimately, the mass of material around the remnant may condense to form a retinue of moons that will orbit around this new planet.”

    [ad_2]

    University of Bristol

    Source link

  • Commonly Used Herbicide is Harmful to Adolescent Brain Function

    Commonly Used Herbicide is Harmful to Adolescent Brain Function

    [ad_1]

    Newswise — Herbicides are the most used class of pesticides worldwide, with uses in agriculture, homes and industry. Exposures to two of the most popular herbicides were associated with worse brain function among adolescents, according to a study led by researchers at the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego.

    In the Oct. 11, 2023 online issue of Environmental Health Perspectives, the researchers reported measuring metabolite concentrations of two commonly used herbicides — glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) — and the insect repellent DEET in urine samples collected in 2016 from 519 adolescents, aged 11 to 17, living in the agricultural county of Pedro Moncayo, Ecuador. Researchers also assessed neurobehavioral performance in five areas: attention and inhibitory control, memory and learning, language, visuospatial processing, and social perception.

    “Many chronic diseases and mental health disorders in adolescents and young adults have increased over the last two decades worldwide, and exposure to neurotoxic contaminants in the environment could explain a part of this increase,” said senior author Jose Ricardo Suarez, M.D., Ph.D., M.P.H., associate professor in the Herbert Wertheim School of Public Health.

    Among the findings:

    • Glyphosate, a nonselective herbicide used in many crops, including corn and soy, and for vegetation control in residential settings, was detected in 98 percent of participants.
    • 2,4-D, a broadleaf herbicide used on lawns, aquatic sites, and agricultural crops, was detected in 66 percent of participants.
    • Higher amounts of 2,4-D in urine were associated with lower neurobehavioral performance in the domains of attention and inhibitory control, memory and learning, and language.
    • Glyphosate concentration in urine was associated with lower scores in social perception only, while DEET metabolites were not associated with neurobehavioral performance.

    Following the introduction of genetically modified, glyphosate-resistant “Roundup-ready” crops in 1996 and 2,4-D resistant crops in 2014, there have been substantial increases in glyphosate and 2,4-D use, making them the most widely used herbicides in the world, wrote the authors.

    “There is considerable use of herbicides and insecticides in agricultural industries in both developed and developing nations around the world, raising exposure potential for children and adults, especially if they live in agricultural areas, but we don’t know how it impacts each stage of life,” said first author Briana Chronister, doctoral candidate in the UC San Diego – San Diego State University Joint Doctoral Program in Public Health.

    Previous studies have linked exposure to some of the most used insecticides to altered neurocognitive performance while other insecticides may also affect mood and brain development. Today, 20 percent of adolescents and 26 percent of young adults have diagnosable mental health conditions such as anxiety, depression, impulsivity, aggression or learning disorders.

    The authors reported that 2,4-D was negatively associated with performance in all five neurobehavioral areas, but statistically significant associations were observed with attention and inhibitory control, memory and learning, and language. Glyphosate had a significant negative association only with social perception, a test that measures the ability to recognize emotions, while DEET metabolites were not associated with neurobehavioral alterations.

    “Hundreds of new chemicals are released into the market each year, and more than 80,000 chemicals are registered for use today,” said Suarez. “Sadly, very little is known about the safety and long-term effects on humans for most of these chemicals. Additional research is needed to truly understand the impact.”

    This research is a study within ESPINA: The Study of Secondary Exposures to Pesticides Among Children and Adolescents, a prospective cohort study funded by the National Institute of Environmental Health Sciences, part of the National Institutes of Health, the National Institute of Occupational Safety and Health, and other private funding sources. ESPINA aims to understand the effect of pesticide exposures on the development of humans from childhood thru adulthood.

    In 2022, Suarez and his team completed year 14 of follow-up of study participants with plans to evaluate whether the observed associations persist into early adulthood.

    Co-authors include: Kun Yang, Audrey R. Yang, Tuo Lin, Xin Tu, Harvey Checkoway, Jose Suarez-Torres, Sheila Gahagan, and Raeanne C. Moore, UC San Diego; Dolores Lopez-Paredes and Danilo Martinez, Fundación Cimas del Ecuador; and Dana Barr, Emory University.

    This research was funded, in part, by the National Institutes of Health (R01ES025792, R01ES030378, R21ES026084, U2CES026560, P30ES019776, 5T32MH122376).

    Disclosures: The authors do not have any conflicts of interest to report.

    DOI: 10.1289/EHP11383

    [ad_2]

    University of California San Diego

    Source link

  • Jet lag disorder associated with shift work can lead to brain changes increasing appetite

    Jet lag disorder associated with shift work can lead to brain changes increasing appetite

    [ad_1]

    Newswise — Scientists have uncovered why night shift work is associated with changes in appetite in a new University of Bristol-led study. The findings, published in Communications Biology, could help the millions of people that work through the night and struggle with weight gain.

    Scientists from Bristol and the University of Occupational and Environmental Health in Japan, sought to understand how ‘circadian misalignment’ — a phenomenon commonly associated with ‘jet-lag’ whereby the body’s biological clock is disrupted — affects the hormones responsible for regulating appetite.

    Prevalent in night shift workers, in this new study, the international team reveal how circadian misalignment can profoundly alter the brain’s regulation of hormones controlling hunger to the detriment of metabolic health.

    The team focused on glucocorticoid hormones in the adrenal gland which regulate many physiological functions including metabolism and appetite. Glucocorticoids are known to directly regulate a group of brain peptides controlling appetitive behaviour, with some increasing appetite (orexigenic) and some decreasing appetite (anorexigenic).

    In an experiment using animal models, comprising a control group and a out-of-phase ‘jet-lagged’ group, the team found misalignment between light and dark cues led the out-of-phase group’s orexigenic hypothalamic neuropeptides (NPY) to become dysregulated, driving an increased desire to eat significantly more during the inactive phase of the day.

    Strikingly, the team discovered that rats in the control group ate 88.4% of their daily intake during their active phase, and only 11.6% during their inactive phase. In contrast, the ‘jet-lagged’ group consumed 53.8% of their daily calories during their inactive phase (without an increase in activity during this time). This equated to nearly five-times more (460% more) than what the control group consumed during the inactive phase.  These results show that it is timing of consumption that has been affected.

    This new discovery revealed how completely, and significantly, disordered the neuropeptides become when daily glucocorticoid levels are out of synch with light and dark cues.  However, the authors suggest the neuropeptides identified in this study may be promising targets for drug treatments adapted to treat eating disorders and obesity.

    Dr Becky Conway-Campbell, Research Fellow in Bristol Medical School: Translational Health Sciences (THS) and the study’s senior author, said: “For people working throughout the night, a reversed body clock can play havoc with their health.

    “For those who are working night shifts long-term, we recommend they try to maintain daylight exposure, cardiovascular exercise and mealtimes at regulated hours. However, internal brain messages to drive increased appetite are difficult to override with ‘discipline’ or ‘routine’ so we are currently designing studies to assess rescue strategies and pharmacological intervention drugs. We hope our findings also provide new insight into how chronic stress and sleep disruption leads to caloric overconsumption.”

    Stafford Lightman, Professor of Medicine at Bristol Medical School: THS and co-senior author on the study, added: “The adrenal hormone corticosterone, which is normally secreted in a circadian manner, is a major factor in the daily control of brain peptides that regulate appetite. Furthermore when we disturb the normal relationship of corticosterone with the day to night light cycle it results in abnormal gene regulation and appetite during the period of time that the animals normally sleep.

    “Our study shows that when we disturb our normal bodily rhythms this in turn disrupts normal appetite regulation in a way that is at least in part a result of desynchrony between adrenal steroid hormone production and the timing of the light and dark cycle.”

    Dr Benjamin Flynn, one of the study’s co-authors who conducted the study while at Bristol but is now based at the University of Bath, added: “This is further evidence of how phase shift ‘jet-lag’ affects feeding behaviours and neuronal gene expression – data important for shift work co-morbidity research.”

    This research was funded by the Medical Research Council.

    Paper

    ‘Phase-shifting the circadian glucocorticoid profile induces disordered feeding behaviour by dysregulating hypothalamic neuropeptide gene expression’ by M Yoshimura, B Flynn, Y Kershaw, Z Zhao, Ueta, S Lightman, R Conway-Campbell et al. in Communications Biology [open access]

    [ad_2]

    University of Bristol

    Source link