High-impact Chronic Pain in a Cohort of Urologic Chronic Pelvic Pain Syndrome Patients: A Retrospective MAPP Research Network Study.

Objectives: An emerging concept in the chronic pain literature, high-impact chronic pain (HICP), refers to pain that occurs very frequently and results in major disruption of daily life. Previous epidemiologic investigations have noted that lower educational attainment, age, and race appear to be associated with the frequency of HICP, but condition-specific investigations of HICP have been less common.

Methods: Here we investigate HICP status and its clinical/demographic correlates in the Multidisciplinary Approach to the study of chronic Pelvic Pain research network Symptom Pattern Study.

Feasibility pilot of a novel coaching intervention to optimize cannabis use for chronic pain management among Veterans.

Introduction: Chronic pain is common among Veterans, some of whom use cannabis for pain. We conducted a feasibility pilot study of a novel coaching intervention to help Veterans optimize use of medical cannabis products for pain management (NCT06320470).

Methods: The intervention drew from scientific literature, consultation with cannabis experts, Veteran input via a Community Advisory Board, and tenets of motivational interviewing.

Racial/ethnic differences in post-acute sequelae of SARS-CoV-2 in children and adolescents in the United States.

Racial/ethnic differences are associated with the symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study with difference-in-differences analyzes to assess these differences in children and adolescents under the age of 21.

Engineered packaging cell line for the enhanced production of baboon-enveloped retroviral vectors.

The baboon endogenous retrovirus (BaEV) glycoprotein is superior to the commonly used vesicular stomatitis virus glycoprotein (VSVg) for retroviral gene transfer into resting hematopoietic stem cells and lymphocyte populations. The derivative BaEVRLess (lacking the R domain) produces higher viral titers compared with wild-type BaEV, but vector production is impaired by syncytia formation and cell death of the HEK293T cells due to the high fusogenic activity of the glycoprotein. This lowers viral titers, leads to increased batch-to-batch variability, and impedes the establishment of stable packaging cell lines essential for the economical production of viral supernatants.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.

Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, and metabolic disorders but has not yet been successfully developed for individuals with the bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function and lead to inefficient translation of the erythroid master regulator GATA1, providing a potential avenue for therapeutic intervention applicable to all patients with DBA, irrespective of the underlying genotype. Here, we report the development of a clinical-grade lentiviral gene therapy that achieves erythroid lineage-restricted expression of GATA1.

When Things Go South, It Does Affect You: Perceptions of Vibrio- Related Occupational Risk and Harm Among Chesapeake Bay, USA,-Based Watermen.

Abstract: Commercial fishing is a dangerous profession with known hazards for musculoskeletal injuries, yet minimal examination of microbiological or attendant psychosocial hazards from water- and food-borne pathogens like Vibrio vulnificus and V. parahaemolyticus exists. Improving knowledge of Vibrio -related hazards addresses Total Worker Health® concerns for commercial fisheries workers.

The case for investment in nutritional interventions to prevent and reduce childhood and adolescent overweight and obesity in Peru: a modelling study.

Background: Between 2006 and 2016 the prevalence of overweight and obesity among children and adolescents aged 5-19 years in Peru increased from 22.7 to 27.0%.

Widespread pain phenotypes impact treatment efficacy results in randomized clinical trials for interstitial cystitis/bladder pain syndrome: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain network study.

Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS).

Fibromyalgia is associated with increased odds of prior pain-precipitated relapse among non-treatment-seeking individuals with opioid use disorder.

Background/objectives: Chronic pain is an opioid use disorder (OUD) treatment barrier and associated with poor outcomes in OUD treatment including relapse. Fibromyalgia is a chronic pain condition related to central nervous system substrates that overlap with the brain disease model of OUD. We know of no studies that have looked at non-treatment seeking individuals, to see if fibromyalgia might represent a barrier to OUD treatment.

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy.

Background: Cerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.

Methods: In a phase 2-3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI).

Pediatric Long COVID Subphenotypes: An EHR-based study from the RECOVER program.

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations.

Research protocol for bridging research, accurate information and dialogue (BRAID)-clinical trials: a mixed-methods study of a community-based intervention to improve trust and diversify participation in clinical trials.

Cultural beliefs, personal experiences, and historic abuses within the healthcare system-rooted in structural racism-all contribute to community distrust in science and medicine. This lack of trust, particularly within underserved communities, contributes to decreased participation in clinical trials and a lack of representation in the data. Open dialogue about community concerns and experiences related to research participation and medical care processes can help build trust and change attitudes and behaviors that affect community health.

UM171 enhances fitness and engraftment of gene-modified hematopoietic stem cells from patients with sickle cell disease.

Hematopoietic stem cell (HSC) transplantation with lentiviral vector (LVV)-transduced autologous cells has proven an effective therapeutic strategy for sickle cell disease (SCD). However, ex vivo culture or proliferative stress associated with in vivo reconstitution may amplify any underlying genetic risk of leukemia. We aimed to minimize culture-induced stress and reduce genomic damage during ex vivo culture and enhance stem cell fitness and reconstitution of SCD CD34+ cells transduced with BCL11A shmiR-encoding LVV.

Solidarity in disaster scholarship.

Disaster scholarship purportedly promotes disaster risk reduction and resists disaster risk creation, thereby deeply engaging with transboundary existential risks, justice, and political power. It is thus a commitment to humanity, and for it to become truly equitable and just, solidarity must lie at its heart. In this paper we connect solidarity with knowledge production and assess the implications of disaster scholarship and the relationships on which it is built.

Substituting Medical Cannabis for Medications Among Patients with Rheumatic Conditions in the United States and Canada.

Objective: There are numerous reports of people substituting medical cannabis (MC) for medications. Our obejctive was to investigate the degree to which this substitution occurs among people with rheumatic conditions.

Methods: In a secondary analysis from a cross-sectional survey conducted with patient advocacy groups in the US and Canada, we investigated MC use and medication substitution among people with rheumatic conditions.

Small towns limit dispersal and reduce genetic diversity in populations of Texas horned lizards.

There is a general expectation that urban populations will be fragmented and the movement of individuals will be restricted leading to low effective population sizes, low genetic diversity, higher inbreeding, and higher differentiation than populations living in more continuous habitat. In this study, we compare the genetic diversity and differentiation of Texas horned lizards that are found in four small towns (Kenedy, Karnes City, Rockdale, and Smithville) in Texas and at Tinker Air Force Base, Oklahoma to populations that occur in 16 natural areas and to an introduced population in South Carolina. We also present more detailed spatial genetic data and home range data for several of the towns.

Self-guided digital behavioural therapy versus active control for fibromyalgia (PROSPER-FM): a phase 3, multicentre, randomised controlled trial.

Background: International guidelines have recommended cognitive behavioural therapy, including acceptance and commitment therapy (ACT), as it offers validated benefits for managing fibromyalgia; however, it is inaccessible to most patients. We aimed to evaluate the effect of a 12-week, self-guided, smartphone-delivered digital ACT programme on fibromyalgia management.

Methods: In the PROSPER-FM randomised clinical trial conducted at 25 US community sites, adult participants aged 22-75 years with fibromyalgia were recruited and randomly assigned (1:1) to the digital ACT group or an active control group that offered daily symptom tracking and monitoring and access to health-related and fibromyalgia-related educational materials.

Post-acute and Chronic Kidney Function Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Initiative.

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI.

Protocol for a pragmatic trial of Cannabidiol (CBD) to improve chronic pain symptoms among United States Veterans.

Background: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential.