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  • Rural jails turn to community health workers to help the newly released succeed

    Rural jails turn to community health workers to help the newly released succeed

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    Garrett Clark estimates he has spent about six years in the Sanpete County Jail, a plain concrete building perched on a dusty hill just outside this small, rural town where he grew up.

    “That’s all I’ve known my whole life,” said Clark, 31, in December.

    Clark was at the jail to pick up his sister, who had just been released. The siblings think this time will be different. They are both sober. Shantel Clark, 33, finished earning her high school diploma during her four-month stay at the jail. They have a place to live where no one is using drugs.

    And they have Cheryl Swapp, the county sheriff’s new community health worker, on their side.

    “She saved my life probably, for sure,” Garrett Clark said.

    Swapp meets with every person booked into the county jail soon after they arrive and helps them create a plan for the day they get out.

    She makes sure everyone has a state ID card, a birth certificate, and a Social Security card so they can qualify for government benefits, apply to jobs, and get to treatment and probation appointments. She helps nearly everyone enroll in Medicaid and apply for housing benefits and food stamps. If they need medication to stay off drugs, she lines that up. If they need a place to stay, she finds them a bed.

    Then Swapp coordinates with the jail captain to have people released directly to the treatment facility. Nobody leaves the jail without a ride and a drawstring backpack filled with items like toothpaste, a blanket, and a personalized list of job openings.

    “A missing puzzle piece,” Sgt. Gretchen Nunley, who runs educational and addiction recovery programming for the jail, called Swapp.

    Swapp also assesses the addiction history of everyone held by the county. More than half arrive at the jail addicted to something.

    Nationally, 63% of people booked into local jails struggle with a substance use disorder — at least six times the rate of the general population, according to the federal Substance Abuse and Mental Health Services Administration. The incidence of mental illness in jails is more than twice the rate in the general population, federal data shows. At least 4.9 million people are arrested and jailed every year, according to an analysis of 2017 data by the Prison Policy Initiative, a nonprofit organization that documents the harm of mass incarceration. Of those incarcerated, 25% are booked two or more times, the analysis found. And among those arrested twice, more than half had a substance use disorder and a quarter had a mental illness.

    “We don’t lock people up for being diabetic or epileptic,” said David Mahoney, a retired sheriff in Dane County, Wisconsin, who served as president of the National Sheriffs’ Association in 2020-21. “The question every community needs to ask is: ‘Are we doing our responsibility to each other for locking people up for a diagnosed medical condition?’”

    The idea that county sheriffs might owe it to society to offer medical and mental health treatment to people in their jails is part of a broader shift in thinking among law enforcement officials that Mahoney said he has observed during the past decade.

    “Don’t we have a moral and ethical responsibility as community members to address the reasons people are coming into the criminal justice system?” asked Mahoney, who has 41 years of experience in law enforcement.

    Swapp previously worked as a teacher’s aide for those she calls the “behavior kids” — children who had trouble self-regulating in class. She feels her work at the jail is a way to change things for the parents of those kids. And it appears to be working.

    Since the Sanpete County Sheriff’s Office hired Swapp last year, recidivism has dropped sharply. In the 18 months before she began her work, 599 of the people booked into Sanpete County Jail had been there before. In the 18 months after she started, that number dropped to 237.

    In most places, people are released from county jails with no health care coverage, no job, nowhere to live, and no plan to stay off drugs or treat their mental illness. Research shows that people newly released from incarceration face a risk of overdose that is 10 times as high as that of the general public.

    Sanpete wasn’t any different.

    “For seven to eight years of me being here, we’d just release people and cross our fingers,” said Jared Hill, the clinical director for Sanpete County and a counselor at the jail.

    Nunley, the programming sergeant, remembers watching people released from jail walk the mile to town with nothing but the clothes they’d worn on the day they were arrested — it was known as the “walk of shame.” Swapp hates that phrase. She said no one has made the trip on foot since she started in July 2022.

    Swapp’s work was initially funded by a grant from the U.S. Health Resources and Services Administration, but it has proved so popular that commissioners in Sanpete County voted to use a portion of its opioid settlement money to cover the position in the future.

    Swapp doesn’t have formal medical or social work training. She is certified by the state of Utah as a community health worker, a job that has become more common nationwide. There were about 67,000 people working as community health workers in 2022, according to the U.S. Bureau of Labor Statistics.

    Evidence is mounting that the model of training people to help their neighbors connect to government and health care services is sound, said Aditi Vasan, a senior fellow at the Leonard Davis Institute of Health Economics at the University of Pennsylvania who has reviewed the research on the relatively new role.

    The day before Swapp coordinated Shantel Clark’s release, she sat with Robert Draper, a man in his 50s with long white hair and bright-blue eyes. Draper has been in and out of jail for decades. He was sober for a year and had been taking care of his ill mother. She kept getting worse. Then his daughter and her child came to help. It was all a little too much.

    “I thought, if I can just go and get high, I can deal with this shit,” said Draper. “But after you’ve been using for 40 years, it’s kinda easy to slip back in.”

    He didn’t blame his probation officer for throwing him back in jail when he tested positive for drugs, he said. But he thinks jail time is an overreaction to a relapse. Draper sent a note to Swapp through the jail staff asking to see her. He was hoping she could help him get out so he could be with his mom, who had just been sent to hospice. He had missed his father’s death years ago because he was in jail at the time.

    Swapp listened to Draper’s story without interruptions or questions. Then she asked if she could run through her list with him so she would know what he needed.

    “Do you have your Social Security card?”

    “My card?” Draper shrugged. “I know my number.”

    “Your birth certificate, you have it?”

    “Yeah, I don’t know where it is.”

    “Driver’s license?”

    “No.”

    “Was it revoked?”

    “A long, long time ago,” Draper said. “DUI from 22 years ago. Paid for and everything.”

    “Are you interested in getting it back?”

    “Yeah!”

    Swapp has some version of this conversation with every person she meets in the jail. She also runs through their history of addiction and asks them what they most need to get back on their feet.

    She told Draper she would try to get him into intensive outpatient therapy. That would involve four to five classes a week and a lot of driving. He’d need his license back. She didn’t make promises but said she would talk to his probation officer and the judge. He sighed and thanked her.

    “I’m your biggest fan here,” Swapp said. “I want you to succeed. I want you to be with your mom, too.”

    The federal grant that funded the launch of Sanpete’s community health worker program is held by the regional health care services organization Intermountain Health. Intermountain took the idea to the county and has provided Swapp with support and training. Intermountain staff also administer the $1 million, three-year grant, which includes efforts to increase addiction recovery services in the area.

    A similarly funded program in Kentucky called First Day Forward took the community health worker model a step further, using “peer support specialists” — people who have experienced the issues they are trying to help others navigate. Spokespeople from HRSA pointed to four programs, including the ones in Utah and Kentucky, that are using their grant money for people facing or serving time in local jails.

    Back in Utah, Sanpete’s new jail captain, Jeff Nielsen, said people in small-town law enforcement weren’t so far removed from those serving time.

    “We know these people,” Nielsen said. He has known Robert Draper since middle school. “They are friends, neighbors, sometimes family. We’d rather help than lock them up and throw away the key. We’d rather help give them a good life.”




    Kaiser Health NewsThis article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

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  • Childhood trauma linked to higher rates of somatic symptoms, study finds

    Childhood trauma linked to higher rates of somatic symptoms, study finds

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    In a recent study published in the JAMA Network Open, a group of researchers investigated the prevalence and severity of somatic symptoms among children and adolescents who have experienced traumatic events in France.

    Study: Somatic and Posttraumatic Stress Symptoms in Children and Adolescents in France. Image Credit: Jan H Andersen / ShutterstockStudy: Somatic and Posttraumatic Stress Symptoms in Children and Adolescents in France. Image Credit: Jan H Andersen / Shutterstock

    Background 

    Somatic symptoms include a variety of physical complaints, such as gastrointestinal issues, body pain, cardiopulmonary disturbances, and fatigue, leading to significant functional impairment and emotional distress, often without a precise medical diagnosis. These symptoms are prevalent in 10% to 25% of adults, with higher occurrences in specialized medical settings and among at-risk groups like Latinx immigrants. There is a strong link between adverse childhood experiences (ACEs) and the development of somatic symptoms, which are associated with chronic physical and mental health problems, including posttraumatic stress disorder (PTSD). These symptoms show gender differences that intensify in adolescence. Further research is needed to better understand the mechanisms linking traumatic experiences to somatic symptoms in youth, enabling more targeted interventions and improved outcomes.

    About the study 

    The present cross-sectional study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)  guidelines. It was conducted at the Nice Pediatric Psychotrauma Center (NPPC) in southern France. With ethical clearance from the National Ethics Committee NORTHWEST III and registration with ClinicalTrials.gov, this study forms part of a broader research program investigating the multifaceted associations of psychological trauma in children. Recruitment occurred throughout 2021, drawing participants from NPPC’s outpatient service. The center, known for its specialized, multidisciplinary approach to pediatric psycho-trauma, integrates expertise from a range of fields, including child psychiatry and psychology, neuropsychology, and pediatric nursing.

    Participants in the study were children and adolescents aged 7 to 17 who had experienced at least one Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 defined traumatic event, with assessments carried out by qualified child psychologists or psychiatrists specializing in trauma. The children, alongside their parents, provided informed consent before participation. The assessment tools used included the Child PTSD Checklist (CPC) for evaluating exposure to traumatic events and the Patient Health Questionnaire (PHQ)-13 questionnaire, which measures the severity of 13 different somatic symptoms ranging from stomach and back pain to fatigue and dizziness. The PHQ-13 assesses symptom severity over the previous week using a Likert scale and has been adapted from the adult version, excluding items irrelevant to children.

    Through comprehensive assessments, the research team sought to identify patterns of single versus multiple traumatic exposures and their impacts on somatic and PTSD symptoms. Statistical analyses were performed to explore these relationships, considering variables such as the number and intensity of somatic symptoms and PTSD symptom severity. 

    Study results 

    The study comprised 363 youths, with a nearly even gender distribution: 174 females (47.9%) and 189 males (52.1%). Participants ranged in age from 7 to 17 years, averaging 13.58 years. They were assessed for their exposure to potentially traumatic events, with 288 (79.3%) directly exposed, 36 (9.9%) indirectly exposed through a close relation, and 39 (10.7%) witnessing such events. The CPC identified 144 youths (39.7%) who met the criteria for PTSD.

    Somatic symptoms were notably more frequent and intense among the PTSD group compared to their peers without PTSD. The most common traumatic events were man-made disasters, including the terrorist attack on July 14, 2016, affecting 200 youths (55.1%); witnessing an assault noted by 109 participants (30.0%); and hospitalization, experienced by 94 youths (25.9%).

    The intensity of PTSS and associated functional impairments were quantitatively higher in the PTSD group, with average scores reflecting significant distress and disruption to daily functioning. In contrast, those in the non-PTSD group reported markedly lower levels of symptomatology and impairment.

    A closer look at the somatic symptomatology revealed that the PTSD group experienced a higher mean intensity and a greater number of somatic complaints. The most significant correlations were between PTSS intensity and symptoms such as stomach pain and headaches, suggesting a direct linkage between trauma exposure and physical manifestations of stress.

    Further analyses explored the impact of experiencing multiple traumatic events. Among participants with cumulative trauma exposures, those with multiple events reported higher levels of both somatic symptoms and overall symptom intensity. This group demonstrated a clear gradient, with increases in the number and severity of symptoms correlating with the number of traumatic events experienced. Lastly, the study’s multiple regression analysis, focusing on somatic symptoms significantly associated with PTSD, revealed that these symptoms could account for 6.5% of the variance in PTSS severity. 

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  • Cruciferous vegetables may offer new hope for inflammatory bowel disease management

    Cruciferous vegetables may offer new hope for inflammatory bowel disease management

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    In a recent review published in the journal Current Developments in Nutrition, researchers assessed the therapeutic potential of cruciferous vegetables and their bioactive compounds in managing inflammatory bowel disease (IBD) using in vitro, in vivo, and clinical models. 

    Review: Current knowledge on the preparation and benefits of cruciferous vegetables as relates to in vitro, in vivo, and clinical models of Inflammatory Bowel Disease. Image Credit: SewCreamStudio / ShutterstockReview: Current knowledge on the preparation and benefits of cruciferous vegetables as relates to in vitro, in vivo, and clinical models of Inflammatory Bowel Disease. Image Credit: SewCreamStudio / Shutterstock

    Background 

    IBD, including Ulcerative Colitis (UC) and Crohn’s Disease (CD), is a chronic condition characterized by persistent inflammation, gastrointestinal distress, and severe tissue damage. UC affects the colon and rectum, while CD involves the distal gut, both resulting in painful symptoms and the need for frequent surgical interventions. IBD’s prevalence, particularly in Europe and North America, poses significant economic and social challenges, aggravated by links to modern lifestyle factors such as dietary changes to ultra-processed foods, urbanization, and stress. Current treatments, focusing on inflammation and microbial imbalances, often diminish in efficacy, highlighting the need for cost-effective management strategies and further research into personalized dietary interventions using bioactive compounds from cruciferous vegetables for improved therapeutic outcomes.

    Introduction to cruciferous vegetables and bioactive compounds

    Cruciferous vegetables belonging to the Brassicaceae family include a variety of nutrient-rich plants such as broccoli, Brussels sprouts, cabbage, and kale. These vegetables are distinguished by their high content of glucosinolates (GSLs), which are sulfur-containing compounds known to influence human health positively. When consumed, GSLs are converted by the enzyme myrosinase into isothiocyanates (ITCs) such as sulforaphane (SFN), compounds that have been extensively studied for their potential to modulate oxidative stress and inflammation- two key pathological aspects of IBD.

    These vegetables also contain other significant bioactive compounds, such as flavonoids and polyphenols. Flavonoids, like quercetin and kaempferol, possess potent antioxidant properties that help scavenge harmful free radicals in the body. Polyphenols, including ferulic acid and sinapic acid, contribute further antioxidant and anti-inflammatory effects that are crucial for managing chronic diseases like IBD. The combined action of these compounds not only helps reduce oxidative stress and inflammation but also aids in strengthening the gut barrier and modulating the gut microbiome, thereby potentially alleviating symptoms of IBD.

    In vitro evidence of cruciferous vegetable efficacy

    Extensive in vitro research has underscored the therapeutic potential of cruciferous vegetables in the context of IBD. Studies using cell cultures have demonstrated that extracts from these vegetables can significantly inhibit the activation of key inflammatory pathways in immune cells. For instance, broccoli-derived nanoparticles have been shown to prevent the activation of dendritic cells and reduce the secretion of pro-inflammatory cytokines. These findings suggest that cruciferous vegetables can modulate immune responses, potentially lowering the incidence or severity of inflammatory processes within the gut.

    Moreover, the anti-inflammatory effects are complemented by the vegetables’ antioxidant properties. For example, studies on broccoli sprouts have highlighted their ability to increase the activity of phase II detoxifying enzymes, enhancing cellular defense mechanisms against oxidative damage. This is particularly important in IBD, where oxidative stress plays a critical role in aggravating intestinal inflammation and damage.

    In vivo studies supporting cruciferous benefits

    Animal studies have provided compelling evidence supporting the beneficial effects of cruciferous vegetables on IBD. Research utilizing different animal models of colitis has shown that diets enriched with cruciferous vegetables can reduce pathological scores and improve symptoms associated with IBD. These dietary interventions have been observed to modify gut microbiota composition favorably, increase the production of short-chain fatty acids, and enhance the intestinal barrier’s integrity.

    For instance, studies involving mice fed with SFN-rich broccoli extracts have reported reduced expression of inflammatory markers like Tumor Necrosis Factor (TNF)-alpha and Interleukin (IL)-6, along with an increase in the protective proteins of the gut barrier such as zonula occludens-1 (ZO-1). These findings indicate not only a reduction in inflammation but also an improvement in the structural components of the gut lining, which are often compromised in IBD patients.

    Clinical insights and future research directions

    Despite robust in vitro and in vivo evidence, clinical studies exploring the effects of cruciferous vegetables on human subjects with IBD are relatively limited. The existing studies highlight the critical role of vegetable preparation and the bioavailability of active compounds in determining their health benefits. For example, the effectiveness of SFN is influenced significantly by how broccoli is prepared and consumed, as cooking can destroy the enzyme myrosinase necessary for SFN’s release.

    Therefore, more clinical trials are needed to assess the impact of these vegetables on IBD comprehensively and to explore how these effects translate from laboratory and animal models to human health. Such studies should focus on various preparation methods, dosages, and consumption patterns to identify the most beneficial approaches for the dietary management of IBD.

    Additionally, future research should aim to understand the individualized responses to cruciferous vegetable intake in different subpopulations of IBD patients. This could help tailor dietary recommendations to enhance individual patient outcomes and develop personalized nutritional therapies that are both effective and manageable over the long term.

    Journal reference:

    • TE Alaba, J.M. Holman, S.L. Ishaq, et al, Current knowledge on the preparation and benefits of cruciferous vegetables as relates to in vitro, in vivo, and clinical models of Inflammatory Bowel Disease., Current Developments in Nutrition, DOI –  10.1016/ j.cdnut.2024.102160, https://cdn.nutrition.org/article/S2475-2991(24)00094-5/fulltext 

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  • GPT-4’s impressive diagnostic skills showcased

    GPT-4’s impressive diagnostic skills showcased

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    In a recent study published in the journal PLOS Digital Health, researchers assessed and compared the clinical knowledge and diagnostic reasoning capabilities of large language models (LLMs) with those of human experts in the field of ophthalmology.

    Study: Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study. Image Credit: ozrimoz / ShutterstockStudy: Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study. Image Credit: ozrimoz / Shutterstock

    Background 

    Generative Pre-trained Transformers (GPTs), GPT-3.5 and GPT-4, are advanced language models trained on vast internet-based datasets. They power ChatGPT, a conversational artificial intelligence (AI) notable for its medical application success. Despite earlier models struggling in specialized medical tests, GPT-4 shows significant advancements. Concerns persist about data ‘contamination’ and the clinical relevance of test scores. Further research is needed to validate language models’ clinical applicability and safety in real-world medical settings and address existing limitations in their specialized knowledge and reasoning capabilities.

    About the study 

    Questions for the Fellowship of the Royal College of Ophthalmologists (FRCOphth) Part 2 examination were extracted from a specialized textbook that is not widely available online, minimizing the likelihood of these questions appearing in the training data of LLMs. A total of 360 multiple-choice questions spanning six chapters were extracted, and a set of 90 questions was isolated for a mock examination used to compare the performance of LLMs and doctors. Two researchers aligned these questions with the categories specified by the Royal College of Ophthalmologists, and they classified each question according to Bloom’s taxonomy levels of cognitive processes. Questions with non-text elements that were unsuitable for LLM input were excluded.

    The examination questions were input into versions of ChatGPT (GPT-3.5 and GPT-4) to collect responses, repeating the process up to three times per question where necessary. Once other models like Bard and HuggingChat became available, similar testing was conducted. The correct answers, as defined by the textbook, were noted for comparison. 

    Five expert ophthalmologists, three ophthalmology trainees, and two generalist junior doctors independently completed the mock examination to evaluate the models’ practical applicability. Their answers were then compared against the LLMs’ responses. Post-exam, these ophthalmologists assessed the LLMs’ answers using a Likert scale to rate accuracy and relevance, blind to which model provided which answer.

    This study’s statistical design was robust enough to detect significant performance differences between LLMs and human doctors, aiming to test the null hypothesis that both would perform similarly. Various statistical tests, including chi-squared and paired t-tests, were applied to compare performance and assess the consistency and reliability of LLM responses against human answers. 

    Study results 

    Out of 360 questions contained in the textbook for the FRCOphth Part 2 examination, 347 were selected for use, including 87 from the mock examination chapter. The exclusions primarily involved questions with images or tables, which were unsuitable for input into LLM interfaces. 

    Performance comparisons revealed that GPT-4 significantly outperformed GPT-3.5, with a correct answer rate of 61.7% compared to 48.41%. This advancement in GPT-4’s capabilities was consistent across different types of questions and subjects, as outlined by the Royal College of Ophthalmologists. Detailed results and statistical analyses further confirmed the robust performance of GPT-4, making it a competitive tool even among other LLMs and human doctors, particularly junior doctors and trainees.

    Examination characteristics and granular performance data. Question subject and type distributions presented alongside scores attained by LLMs (GPT-3.5, GPT-4, LLaMA, and PaLM 2), expert ophthalmologists (E1-E5), ophthalmology trainees (T1-T3), and unspecialised junior doctors (J1-J2). Median scores do not necessarily sum to the overall median score, as fractional scores are impossible.Examination characteristics and granular performance data. Question subject and type distributions presented alongside scores attained by LLMs (GPT-3.5, GPT-4, LLaMA, and PaLM 2), expert ophthalmologists (E1-E5), ophthalmology trainees (T1-T3), and unspecialised junior doctors (J1-J2). Median scores do not necessarily sum to the overall median score, as fractional scores are impossible. 

    In the specifically tailored 87-question mock examination, GPT-4 not only led among the LLMs but also scored comparably to expert ophthalmologists and significantly better than junior and trainee doctors. The performance across different participant groups illustrated that while the expert ophthalmologists maintained the highest accuracy, the trainees approached these levels, far outpacing the junior doctors not specialized in ophthalmology.

    Statistical tests also highlighted that the agreement between the answers provided by different LLMs and human participants was generally low to moderate, indicating variability in reasoning and knowledge application among the groups. This was particularly evident when comparing the differences in knowledge between the models and human doctors.

    A detailed examination of the mock questions against real examination standards indicated that the mock setup closely mirrored the actual FRCOphth Part 2 Written Examination in difficulty and structure, as agreed upon by the ophthalmologists involved. This alignment ensured that the evaluation of LLMs and human responses was grounded in a realistic and clinically relevant context.

    Moreover, the qualitative feedback from the ophthalmologists confirmed a strong preference for GPT-4 over GPT-3.5, correlating with the quantitative performance data. The higher accuracy and relevance ratings for GPT-4 underscored its potential utility in clinical settings, particularly in ophthalmology.

    Lastly, an analysis of the instances where all LLMs failed to provide the correct answer did not show any consistent patterns related to the complexity or subject matter of the questions. 

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  • Study reveals key protein’s role in balancing immune response to viral infections

    Study reveals key protein’s role in balancing immune response to viral infections

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    Researchers have revealed the regulatory mechanism of a specific protein that plays a key role in balancing the immune response triggered by viral infections in mammal cells. These findings could help drive the development of antiviral therapies and nucleic acid medicines to treat genetic disorders.

    For cells to protect themselves from viral infections, a series of immune responses typically occur, including programmed cell death called apoptosis and interferon signaling. While apoptosis is a normal process, which occurs with or without the presence of viral molecules, following a cascade of steps to end with the death of a cell -; which might not sound advantageous to the host -; it can help prevent the reproduction of abnormal cells, including those infected by viruses, and eliminate them from the body. Interferons, on the other hand, are proteins produced by animal cells in response to a viral infection to protect the cell against viral attacks and prevent the virus from replicating. The regulatory mechanism of how cells maintain a balance between apoptosis and interferon response to efficiently suppress viral replication during infection, however, remained unclear.

    In the current study, a team including researchers from the University of Tokyo focused on a specific protein, TRBP, which is also classified as a type of protein called an RNA silencing factor.

    RNA is a nucleic acid, an organic compound found in living cells and viruses, which controls protein synthesis and the genetic makeup of many viruses. RNA synthesizes proteins through a process known as translation, by reading genetic sequences and translating them into instructions for the cells to create proteins, which are mostly responsible for the overall structure and function of the organism, whether it’s a plant or animal.

    RNA silencing, also known as RNA interference, is a way that plants and invertebrate animals can protect themselves from viruses by cleaving viral RNA to repress viral replication.

    This study provides a significant insight that clearly revealed the protein related to the RNA silencing mechanism, which is known to be an antiviral mechanism in a plant or invertebrate, is strongly related to antiviral response also in mammals by another mechanism.”

    Tomoko Takahashi, co-author, visiting researcher at the University of Tokyo and assistant professor at Saitama University, Japan

    Though it is widely understood that RNA silencing is a mechanism that operates under normal conditions to control gene expression (if the gene is “turned on” to provide instructions for the cell to assemble the specific protein it encodes), it’s still unclear how this process occurs under the stress of viral infection.

    So the researchers looked at TRBP (an abbreviation for TAR RNA-binding protein), which has shown a significant role in RNA silencing during a viral infection.

    This protein interacts with a virus sensor protein early on in the phases of infection in human cells. In the later stages of viral infection, proteins called caspases are activated, and this type of protein is chiefly responsible for triggering cell death.

    “RNA silencing and interferon signaling were previously considered as independent pathways, but multiple reports, including ours, have demonstrated crosstalk between them,” said Kumiko Ui-Tei, another co-author and associate professor from the University of Tokyo (at the time of the study).

    This functional conversion of TRBP triggered by viral infection is the basis of regulating interferon response and apoptosis, with TRBP irreversibly increasing the programmed cell death of infected cells, while reducing interferon signaling. TRBP works on the cell by inducing cell death, stopping the viral replication entirely, in contrast to the interferon response pathway, which just subdues viral replication instead of eliminating the infected cells.

    “The ultimate goal is understanding the molecular mechanism underlying the antiviral defense system, orchestrated through the interplay between internal and external RNA pathways in human cells,” said Takahashi.

    By gaining a deeper understanding of how defenses against viruses work on a molecular level, the researchers aim to drive the development of nucleic acid medicines. These medicines utilize targeting and inhibition approaches similar to the antiviral response of RNA silencing, and they hold promise of being increasingly useful in treating a wider range of patients afflicted with viral infections, genetic mutations and genetic defects.

    This study was conducted in collaboration with Saitama University, Chiba University, Kyoto University and Maebashi Institute of Technology in Japan.

    Source:

    Journal reference:

    Shibata, K., et al. (2024) Caspase-mediated processing of TRBP regulates apoptosis during viral infection. Nucleic Acids Research. doi.org/10.1093/nar/gkae246.

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  • New insights to optimize telehealth for diabetes care

    New insights to optimize telehealth for diabetes care

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    Grocery stores, airports and beaches aren’t great places to have telehealth visits with your endocrinologist. But home can be one of the best locations, giving a doctor helpful insights into a patient’s home environment, which can positively impact their care.

    This is just one finding shared in a new study published this week in The Journal of Clinical Diabetes.

    Researchers interviewed clinicians and staff who provide diabetes care through telehealth across four University of California academic medical centers: UC Davis Health, UCSF Health, UCLA Health and UC San Diego Health. Researchers asked open-ended questions to learn how telehealth is used, challenges faced, helpful practices and plans for the future.

    These are critical and timely questions since telehealth remains an important way to provide care in the wake of the COVID-19 pandemic. But there is limited data about how to optimize it for specific types of care. We asked the people who have the most experience in this area to identify best practices which can be used, further studied, and refined moving forward.”

    Stephanie Crossen, UC Davis pediatric endocrinologist and senior author of the study

    The study suggests several important strategies to improve telehealth operations:

    1. Dedicated staff support is essential to obtain data from patients’ devices (like remote glucose monitors) ahead of telehealth visits. This can improve access to care for individuals with limited digital literacy, save clinician time during visits and prevent unnecessary rescheduling of appointments.
    2. Efficient workflows around scheduling follow-up visits are needed to ensure people don’t experience lapses in care.
    3. Finding the best ways to facilitate team-based diabetes care is key. For a diabetes management telehealth visit, this may include a nurse, dietitian, social worker, pharmacist or educator, in addition to the primary clinician. It is important to create workflows that support this effort.

    Interviewees also said telehealth visits can provide a good opportunity to review and discuss the impact of the home environment on diabetes self-care. Through screen sharing, clinicians can also review trends in a patient’s glucose data and discuss daily management successes or challenges.

    Finally, those interviewed also noted the need for clear patient guidelines about appropriate timing and physical setting for joining telehealth visits to make them efficient and effective. For example, visits while driving or at a large group event were not advised.

    I hope the findings of our study will spark discussion around how we can optimize telehealth and take advantage of its unique capabilities to improve patient care, rather than trying to replicate the in-person visit.”

    Sarah Haynes, assistant professor from the UC Davis Department of Pediatrics and lead author of the study

    Other study authors are Miriam Sarkisian of the UC Davis Center for Health and Technology; Aaron Neinstein and Polly Teng of UCSF’s Department of Medicine; Jenise Wong of UCSF’s Department of Pediatrics; and James Marcin of UC Davis Department of Pediatrics.

    This study was supported by a research award from the Children’s Miracle Network at UC Davis. Crossen also receives support from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH) through grant number K23DK125671.

    Source:

    University of California – Davis Health

    Journal reference:

    Haynes, S. C., et al. (2024) From Surviving to Thriving: A Qualitative Study of Adapting Telehealth Systems for Specialty Diabetes Care Across Four California Medical Centers. Clinical Diabetes. doi.org/10.2337/cd23-0108.

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  • Dietary treatments outperform medications for IBS management

    Dietary treatments outperform medications for IBS management

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    Dietary treatment is more effective than medications in irritable bowel syndrome (IBS). These are the findings of a study conducted at the University of Gothenburg. With dietary adjustments, more than seven out of ten patients had significantly reduced symptoms.

    Irritable bowel syndrome (IBS) is a common diagnosis that causes abdominal pain, gas and abdominal bloating, diarrhea, and constipation, in various combinations and with varying degrees of severity.

    Treatment often consists of dietary advice such as eating small and frequent meals and avoiding excessive intake of food triggers such as coffee, alcohol and fizzy drinks. Patients may also be given medications to improve specific symptoms, such as gas or constipation, diarrhea, bloating or abdominal pain. Antidepressants are sometimes used to improve symptoms in IBS. 

    The current study, published in The Lancet Gastroenterology & Hepatology, compared three treatments: two dietary and one based on use of medications. The participants were adult patients with severe or moderate IBS symptoms at Sahlgrenska University Hospital in Gothenburg.

    More symptom relief after dietary adjustment

    The first group was given traditional IBS dietary advice, focusing on eating behavior combined with low intake of fermentable carbohydrates, known as FODMAPs. These include e.g. products with lactose, legumes, onions, and grains, which ferment in the colon and can cause pain in IBS.

    The second group received a dietary treatment low in carbohydrates and proportionally high in protein and fat. In the third group, the best possible medication was given based on the patient’s most troublesome IBS symptoms.

    Each group included around 100 participants and the treatment periods lasted four weeks. When the researchers then examined how well the participants responded to the treatments, using an established IBS symptom scoring scale, the results were clear.

    Of those who received traditional IBS dietary advice and low content of FODMAPs, 76% had significantly reduced symptoms. In the group receiving low carbohydrates and high protein and fat, the proportion was 71%, and in the medication group 58%.

    All groups reported significantly better quality of life, less physical symptoms and less symptoms of anxiety and depression.

    The importance of personalization

    At a six-month follow-up, when participants in the dietary groups had partially returned to their previous eating habits, a large proportion still had clinically significant symptom relief; 68% in the traditional dietary advice and low FODMAP group, and 60% in the low-carbohydrate diet group.

    The study was led by Sanna Nybacka, Researcher and Dietician, Stine Störsrud, Associate Professor, and Magnus Simrén, Professor and Senior Consultant, all at Sahlgrenska Academy, University of Gothenburg.

    With this study, we can show that diet plays a central role in the treatment of IBS, but that there are several alternative treatments that are effective.”


    Sanna Nybacka, Researcher and Dietician

    “We need more knowledge about how to best personalize the treatment of IBS in the future and we will further investigate whether there are certain factors that can predict whether individuals will respond better to different treatment options,” she concludes.

    Source:

    Journal reference:

    Nybacka, S., et al. (2024) A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARBIS): a single-centre, single-blind, randomised controlled trial. The Lancet Gastroenterology & Hepatology. doi.org/10.1016/S2468-1253(24)00045-1.

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  • Rice University bioengineers receive $1.4M to combat osteoarthritis

    Rice University bioengineers receive $1.4M to combat osteoarthritis

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    Bioengineers at Rice University have been awarded $1.4 million as part of a multi-center consortium funded by the Advanced Research Projects Agency for Health (ARPA-H) to develop strategies for reversing the effects of osteoarthritis.

    We’re thrilled to be a part of this collaborative effort to tackle one of the most challenging degenerative joint diseases and develop, test and commercialize solutions for patients.”


    Antonios Mikos, the Louis Calder Professor of Chemical Engineering and professor of bioengineering and materials science and nanoengineering

    APRA-H is part of the National Institutes of Health, and the osteoarthritis funding is administered through its National Initiative for Transforming Research Outcomes program. Mikos’ collaborator on the project is Vasiliki Kolliopoulos, a Rice Academy Postdoctoral Fellow in his lab.

    According to the Centers for Disease Control and Prevention, 32.5 million people in the U.S. and 500 million globally suffer from the degenerative joint disease known as osteoarthritis.

    The consortium, named Orchestrating Multifaceted Engineering for Growing Artificial Joints (OMEGA), is led by Case Western Reserve University in Cleveland. Overall, OMEGA has been awarded $47.7 million for two phases of research spanning five years.

    Various research teams within OMEGA will investigate and integrate perspectives including biomechanics, regenerative medicine, computational modeling and clinical practice to develop equitable interventions targeting osteoarthritis in patients. As part of the program, 40 patients within five years will have knee replacements with “live joints,” or biocompatible bone and cartilage grown from human cells that can restore natural function. The goal is to scale up the technology to make treatment available to patients commercially.

    “Most of us know someone who has this degenerative joint disease. The potential treatment outcomes from this research could improve the quality of life for millions suffering with osteoarthritis,” said

    Mikos, director of the Biomaterials Lab, the Center for Excellence in Tissue Engineering and the J.W. Cox Laboratory for Biomedical Engineering at Rice.

    The Biomaterials Lab will provide state-of-the-art equipment and resources for the design and fabrication of 3D-printed scaffolds, crucial for the creation of live joints. Uday Jammalamadaka, manager of the Biomaterials Lab, will also contribute to the project.

    Current treatment for osteoarthritis offers neither a permanent cure nor solutions without negative effects. In 2020, 1.5 million Americans underwent hip and knee replacements, a number expected to increase by 11% annually to about 5 million procedures by 2040 as the aging population increases and incidence of obesity grows.

    Prosthetic implants presently have a short- to medium-term life cycle, lasting about 20 years. Additional surgery is required as the implants wear out.

    Other members of the consortium include Colorado State University, Ohio State University, Washington State University, the Boston biotech firm Sapphiros AI Bio, University Hospitals Medical Center of Cleveland, the Louis Stokes Cleveland VA Medical Center and Massachusetts General Hospital.

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  • ChatGPT shows promise in polypharmacy management

    ChatGPT shows promise in polypharmacy management

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    Polypharmacy, or the concurrent use of five or more medications, is common in older adults and increases the risk of adverse drug interactions. While deprescribing unnecessary drugs can combat this risk, the decision-making process can be complex and time-consuming. Increasingly, there is a need for effective polypharmacy management tools that can support short-staffed primary care practitioners.

    In a new study, researchers from the Mass General Brigham MESH Incubator found that ChatGPT, a generative artificial intelligence (AI) chatbot, showed promise as a tool to manage polypharmacy and deprescription. These findings, published April 18th in the Journal of Medical Systems, demonstrate the first use case of AI models in medicine management.

    To evaluate its utility, the investigators provided ChatGPT with different clinical scenarios and asked it a set of decision-making questions. Each scenario featured the same elderly patient taking a mixture of medications but included variations in cardiovascular disease history (CVD) and degree of impairment in activities of daily living (ADL).

    When asked yes or no questions about reducing prescribed drugs, ChatGPT consistently recommended deprescribing medications in patients without a history of CVD. However, it was more cautious when overlying CVD was introduced, and more likely to keep the patient’s medication regimen unchanged. In both cases, the researchers observed that ADL impairment severity did not seem to affect decision outcomes.

    The team also noted that ChatGPT had a tendency to disregard pain and favored deprescribing pain medications over other drug types like statins or antihypertensives. In addition, ChatGPT responses varied when presented with the same scenario in new chat sessions -; which the authors suggest could reflect inconsistency in commonly reported clinical deprescribing trends on which the model was trained.

    More than 40 percent of older adults meet the criteria for polypharmacy. The rate of seniors on Medicare seeing more specialists on their care teams has increased in recent years, leaving primary care providers to oversee medication management. An effective AI tool could help aid this practice, according to the researchers. 

    Our study provides the first use case of ChatGPT as a clinical support tool for medication management. While caution should be taken to increase accuracy of such models, AI-assisted polypharmacy management could help alleviate the increasing burden on general practitioners. Further research with specifically trained AI tools may significantly enhance the care of aging patients.”


    Marc Succi, MD, Senior Corresponding Author, Associate Chair of Innovation and Commercialization at Mass General Brigham Radiology and Executive Director of the MESH Incubator

    Arya Rao, lead author, MESH researcher and Harvard Medical student, added “Our findings suggest that AI-based tools can play an important role in ensuring safe medication practices for older adults; it is imperative that we continue to refine these tools to account for the complexities of medical decision-making.”

    Source:

    Journal reference:

    Rao, A., et al. (2024) Proactive Polypharmacy Management Using Large Language Models: Opportunities to Enhance Geriatric Care. Journal of Medical Systems. doi.org/10.1007/s10916-024-02058-y.

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  • Discovery of new vascular cell type may pave way for novel strategies to treat cardiovascular diseases

    Discovery of new vascular cell type may pave way for novel strategies to treat cardiovascular diseases

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    Cardiovascular diseases, including stroke and myocardial infarction, are the world’s leading causes of mortality, accounting for over 18 million deaths a year. A team of KIT researchers has now identified a new cell type in blood vessels responsible for vascular growth. This discovery may allow for novel therapeutic strategies to treat ischemic cardiovascular diseases, i.e. diseases that are caused by reduced or absent blood flow. Nature Communications (DOI: 10.1038/s41467-024-47434-x)

    In our body, a large network of blood vessels distributes blood across our organs and thereby ensures that the active cells are supplied with sufficient oxygen and nutrients to function and to maintain heart beat and brain activities for example. Occlusion of blood vessels and compromising oxygen delivery may cause neuronal or cardiac cell death culminating in stroke or heart attack. Revascularization , i. e. restoring vascular perfusion and promoting tissue regeneration, requires functional blood vessels, but how to effectively revascularize organs still is an unsolved clinical question.

    Since each organ fulfills a different physiological function, vascular branching patterns differ across organs. It has long been a mystery how such unique, so-called organo-typical vascular structures develop.

    From a therapeutic point of view, it is believed that understanding the organ-specific molecular control of vascular growth and patterning could open the doors for developing personalized medicine strategies to combat cardiovascular and neurodegenerative diseases and cancer.

    Pioneer cells move inside the vessel walls

    Scientists of the KIT led by Professor Ferdinand le Noble, Head of the Department of Cell and Developmental Biology and Director of the Zoological Institute of KIT, now discovered that one crucial element contributing to organ-dependent variability in vascular branching involves the activation of a novel vascular cell type they coined endothelial L-tip cell or pioneer cell. Pioneer cells reside inside the inner layer that lines the blood vasculature, the so-called endothelium.

    Using high-end imaging techniques, the scientists found that pioneer cells move inside the vessel wall. Once they come into contact with specific signals produced by cells in the surrounding organ, pioneer cells start to make new blood vessels. To elucidate which cells produce such signals and how these signals are sensed to promote pioneer cell differentiation, the scientists used a recently developed technique called single cell sequencing.

    Molecular cocktail encodes the time and place of blood vessel formation

    Dr. Laetitia Preau, first author of the paper, explains: “Single cell sequencing combines detailed RNA sequencing of individual cells with bio-informatic analyses and allows precise identification of cell subtypes and the molecules these cells produce for cell-to-cell communication. Using this technique, we discovered that the vascular patterning is encoded by a distinct set of molecules that can only be sensed by a subset of endothelial cells to promote vessel growth.”

    The cells in the tissue produce an organ-specific set of molecules that encode the instruction how to make a new blood vessel at that particular place and time. Once the prospective pioneer cell senses and unravels this specific tissue-derived molecular code, it will initiate the vascular growth process.

    Foundations for new therapeutic approaches

    It turned out that several organ-specific vascular growth code molecules are drug-targetable, i.e. react to externally added chemicals.

    To explore the therapeutic avenues, we are collaborating with chemists, tissue engineers, and artificial intelligence (AI) specialists at the 3ROCKIT platform of the Health Technologies Center established recently at Karlsruhe Institute of Technology (KITHealthTech). We hope to identify novel smart molecules to target the vascular growth process that may benefit patients suffering from ischemic cardiovascular diseases, such myocardial infarction and stroke, as well as from certain forms of cancer.”


    Professor Ferdinand le Noble

    The study was financed by the German Research Foundation (DFG) and carried out by KIT in cooperation with the German Center for Cardiovascular Research (DZHK) at its partners sites in Heidelberg and Munich and the Max Planck Institute for Molecular Biomedicine in Münster.

    Source:

    Karlsruhe Institute of Technology

    Journal reference:

    Préau, L., et al. (2024). Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype. Nature Communications. doi.org/10.1038/s41467-024-47434-x.

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