Continent-wide genomic analysis of the African buffalo (Syncerus caffer).

The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided little support for the currently described four subspecies. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

Case report: Microsatellite instability determination is not always black and white in Lynch syndrome diagnosis.

Introduction: Microsatellite instability (MSI) is a genetic marker that is useful in the detection and treatment of Lynch syndrome (Sd). Although conventional techniques such as immunohistochemistry (IHC) and polymerase chain reaction (PCR) are the standards for MSI detection, the advent of next-generation sequencing (NGS) has offered new possibilities, especially with circulating DNA. Case report: We present the case of a 26-year-old patient with Lynch Sd and a BRAF-mutated metastatic colon cancer. The discordant MSI results between the conventional methods and NGS posed challenges in making treatment decisions. Subsequent NGS analysis revealed a high MSI status, leading to participation in an immunotherapy trial, with remarkable clinical response. Conclusion: This case emphasizes the importance of comprehensive molecular profiling and strong interdisciplinary collaborations, especially in cases with ambiguous MSI results.

Cultivating Comfort: Examining Participant Satisfaction with Hypnotic Communication Training in Pain Management.

Context: One in four Canadians experiences chronic pain, yet insufficient services and restrictions surrounding prevailing treatments result in inadequate management and significant negative consequences for these individuals. Previous work indicates that hypnotic communication represents a promising complementary treatment; however, training protocols for healthcare professionals are underdeveloped and understudied. Aim: To evaluate the level of satisfaction for a training program on hypnotic communication in pain management clinics. Design: Qualitative study. Methods: Six health professionals who first completed the hypnotic communication training participated in 30 minutes virtual semi-structured interviews. These testimonials allowed them to elaborate on their user experience and potential areas for improvement. Thematic analysis using qualitative data management software NVIVO was conducted on the interview data. Results: Two themes emerged from the interviews. 1) Satisfaction: Participants expressed satisfaction on various structural aspects of the training, including the provided materials, atmosphere, training structure, presentation modalities, practical workshops, acquired knowledge, trainer quality, and training duration. 2) Areas for Improvement: Five main improvement suggestions were identified (providing more material; more practical workshops, more concrete and adapted; testimonials from former patients; follow-up training meeting; and continuing education). Implications for the Profession and/or Patient Care and Conclusion: The results improved the training program to help minimized inherent biases related to this technique, cut associated costs, and identify reasons that would explain its underutilization among medical professionals in Quebec. Our work highlights that healthcare professionals in chronic pain management clinics (eg, respiratory therapists, nurses) can incorporate this simple hypnotic communication technique into their usual care and contribute to the well-being of patients. Impact: This study aimed to address the lack of training protocols for healthcare professionals, that are underdeveloped and understudied. The main findings on participant' satisfaction and the areas of improvement for the training will help the refinement of the training to better suit healthcare professional's needs in hospitals and chronic pain facilities.

What is known about the role of external facilitators during the implementation of complex interventions in healthcare settings? A scoping review.

OBJECTIVE: To synthesise current knowledge about the role of external facilitators as an individual role during the implementation of complex interventions in healthcare settings. DESIGN: A scoping review was conducted. We reviewed original studies (between 2000 and 2023) about implementing an evidence-based complex intervention in a healthcare setting using external facilitators to support the implementation process. An information specialist used the following databases for the search strategy: MEDLINE, CINAHL, APA PsycINFO, Academic Search Complete, EMBASE (Scopus), Business Source Complete and SocINDEX. RESULTS: 36 reports were included for analysis, including 34 different complex interventions. We performed a mixed thematic analysis to synthesise the data. We identified two primary external facilitator roles: lead facilitator and process expert facilitator. Process expert external facilitators have specific responsibilities according to their role and expertise in supporting three main processes: clinical, change management and knowledge/research management. CONCLUSIONS: Future research should study processes supported by external facilitators and their relationship with facilitation strategies and implementation outcomes. Future systematic or realist reviews may also focus on outcomes and the effectiveness of external facilitation.

The Influence of Disulfide, Thioacetal and Lanthionine-Bridges on the Conformation of a Macrocyclic Peptide.

Cyclisation of peptides by forming thioether (lanthionine), disulfide (cystine) or methylene thioacetal bridges between side chains is established as an important tool to stabilise a given structure, enhance metabolic stability and optimise both potency and selectivity. However, a systematic comparative study of the effects of differing bridging modalities on peptide conformation has not previously been carried out. In this paper, we have used the NMR deconvolution algorithm, NAMFIS, to determine the conformational ensembles, in aqueous solution, of three cyclic analogues of angiotensin(1-7), incorporating either disulfide, or non-reduceable thioether or methylene thioacetal bridges. We demonstrate that the major solution conformations are conserved between the different bridged peptides, but the distribution of conformations differs appreciably. This suggests that subtle differences in ring size and bridging structure can be exploited to fine-tune the conformational properties of cyclic peptides, which may modulate their bioactivities.

Individual health insurance data of antibiotic delivery in previous months as a tool to predict bacterial resistance of urinary tract infection: A prospective cohort study.

OBJECTIVES: We aimed to quantify the individual risk of antimicrobial resistance among patients with community-acquired Escherichia coli urinary tract infection (UTI) according to their antibiotic exposure over the previous 18 months. PATIENTS AND METHODS: French patients were prospectively recruited in two centers in 2015-2017. Resistance of isolates to amoxicillin (AMX), amoxicillin-clavulanate (AMC), third-generation cephalosporins (3GC), trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (FQ) and fosfomycin (FOS) was analysed according to previous intra-class and inter-class antibiotic exposure documented in health insurance files. RESULTS: Previous antibiotic exposure was found in 588 (81.4 %) of the 722 UTI cases analysed (564 patients). Recent exposure (three months before UTI) was associated with stronger intra-class impact on E. coli resistance compared to remote exposure (18 months before UTI) for AMX, AMC, FQ and TMP-SMX, with respective adjusted odds ratios [95 % confidence interval] of 1.63 [1.20-2.21], 1.59 [1.02-2.48], 3.01 [1.90-4.77], and 2.60 [1.75-3.87]. AMX, FQ, and TMP-SMX also showed significant inter-class impact. Resistance to 3GC was not significantly associated with intraclass exposure (adjusted OR: 0.88 [0.41-1.90]). FOS resistance was remarkably low (0.4 %). Duration of the antibiotic-free period required for resistance risk to drop below 10 %, the threshold for empirical use in UTI, was modelled as < 1 month for 3GC, >18 months for AMX and TMP-SMX and uncertain for AMC (5.2 months [2.3 to > 18]) and FQ (17.4 months [7.4 to > 18]). CONCLUSIONS: Resistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery.

Supra-inguinal Inflow for Distal Bypasses Have Acceptable Patency and Limb Salvage Rates.

OBJECTIVE: There is a paucity of data evaluating outcomes of lower extremity bypass (LEB) using supra-inguinal inflow for revascularization of infra-inguinal vessels. The purpose of this study is to report outcomes after LEB originating from aortoiliac arteries to infra-femoral targets. METHODS: The Vascular Quality Initiative database (2003-2020) was queried for patients undergoing LEB from the aortoiliac arteries to the popliteal and tibial arteries. Patients were stratified into three cohorts based on outflow targets (above-knee popliteal, below-knee popliteal and tibial arteries). Perioperative and 1-year outcomes including primary patency, amputation-free survival, and major adverse limb events (MALEs) were compared. A Cox proportional hazards model was used to estimate the independent prognostic factors of outcomes. RESULTS: Of 403 LEBs, 389 (96.5%) originated from the external iliac artery, while the remaining used the aorta or common iliac artery as inflow. In terms of the distal target, the above knee popliteal was used in 116 (28.8%), the below knee popliteal in 151 (27.5%), and tibial vessels in 136 (43.7%) cases. Below-knee popliteal and tibial bypasses, compared to above knee popliteal bypasses, were more commonly performed in patients with chronic limb-threatening ischemia (69.5% and 69.9% vs 48.3%; P < .001). Vein conduit was more often used for tibial bypass than for above- and below-knee popliteal bypasses (46.3% vs 21.9% and 16.3%; P < .001). In the perioperative period, below-knee popliteal and tibial bypass patients had higher reoperation rates (16.9% and 13.2% vs 5.2%; P = .02) and lower primary patency (89.4% and 89% vs 95.7%; P = .04) than above-knee bypass patients. At 1 year, compared with above-knee popliteal bypasses, below-knee and tibial bypasses demonstrated lower primary patency (81.9% vs 56.7% vs 52.4%, p <.001) and freedom from MALE (77.6% vs 70.2% vs 63.1%, p = .04), although amputation free survival was not significantly different (89.7% vs 90.6% vs 83.8%, p = 0.19) .On multivariable analysis, compared with above-knee popliteal bypasses, tibial bypasses were independently associated with increased loss of primary patency (hazard ratio 1.9, 95% confidence interval, 1.03-3.51, p = .04). Sub-analysis of patients with CLTI, demonstrated significantly higher primary patency in the AK popliteal cohort at discharge and one-year, but no difference in amputation free-survival or freedom from MALE between the cohorts at follow-up. CONCLUSIONS: LEB with supra-inguinal inflow appear to have acceptable rates of 1-year patency and limb salvage in patients at high risk of bypass failure. Tibial outflow target was independently associated with worse primary patency but not with MALE or AFS.

Trace elements alone or in mixtures associated with unconventional natural gas exploitation affect rat fetal steroidogenesis and testicular development in vitro.

Biomonitoring studies have shown that pregnant women living in regions of unconventional natural gas (UNG) exploitation have higher levels of trace elements. Whether developmental endocrine disruption can be expected at these exposure levels during pregnancy is unclear. In this study, we aimed to test the impact of five trace elements alone or in mixtures using in vitro cell- and tissue-based assays relevant to endocrine disruption and development. Manganese, aluminum, strontium, barium, and cobalt were tested at concentrations including those representatives of human fetal exposure. Using transactivation assays, none of the tested elements nor their mixture altered the human estrogen receptor 1 or androgen receptor genomic signalling. In the rat fetal testis assay, an organ culture system, cobalt (5 µg/l), barium (500 µg/l) and strontium (500 µg/l) significantly increased testosterone secretion. Cobalt and strontium were associated with hyperplasia and/or hypertrophy of fetal Leydig cells. Mixing the five elements at concentrations where none had an effect individually stimulated testosterone secretion by the rat fetal testis paralleled by the significant increase of 3ß-hydroxysteroid dehydrogenase protein level in comparison to the vehicle control. The mechanisms involved may be specific to the fetal testis as no effect was observed in the steroidogenic H295R cells. Our data suggest that some trace elements in mixture at concentrations representative of human fetal exposure can impact testis development and function. This study highlights the potential risk posed by UNG operations, especially for the most vulnerable populations, pregnant individuals, and their fetus.

[Medico-economic evaluation of the PRADO-BPCO post-exacerbation support program]. / Évaluation médicoéconomique du PRADO-BPCO, programme d'accompagnement post-exacerbation.

INTRODUCTION: The "Programme d'Accompagnement du retour à Domicile" (PRADO) COPD is a home discharge support program dedicated to organizing care pathways following hospitalization for COPD exacerbation. This study aimed at assessing its medico-economic impact. METHODS: This was a retrospective database study of patients included in the PRADO BPCO between 2017 and 2019. Data were extracted from the National Health Data System. A control group was built using propensity score matching. Morbi-mortality and costs (national health insurance perspective) were measured during the year following hospitalization. RESULTS: While the proportion of patients with a care pathway complying with recommendations from the National Health Authority was higher in the PRADO group, there was no significant effect on mortality and 12-month rehospitalization. In the PRADO group, the rehospitalization rate was lower when the care pathway was optimal. Healthcare costs per patient were 670 € higher in the PRADO group. CONCLUSIONS: The PRADO COPD improves quality of care but without decreasing rehospitalizations and mortality, although rehospitalizations did decrease among PRADO group patients benefiting from an optimal care pathway.

Optimal medical therapy is lacking in patients undergoing intervention for symptomatic carotid artery stenosis and protects against larger areas of cerebral infarction.

OBJECTIVES: Carotid interventions are indicated for both patients with symptomatic and a subset of patients with severe asymptomatic carotid artery stenosis (CAS). Symptomatic CAS accounts for up to 12%-25% of overall carotid interventions, but predictors of symptomatic presentation remain poorly defined. The aim of this study was to identify factors associated with symptomatic CAS in our patient population. METHODS: Between January 2015 and February 2022, an institutional retrospective cohort study of prospectively collected data on patients undergoing interventions for CAS was performed. Procedures included carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TF-CAS). Demographic data, comorbidities, procedural details, and anatomic features from various imaging modalities were collected. Comparisons were made between symptomatic (symptoms within the prior 6 months) and asymptomatic patients. RESULTS: During the study period, 279 patients who underwent intervention for symptomatic CAS were paired with a randomly selected cohort of 300 patients who underwent intervention for asymptomatic CAS from a total patient cohort of 1143 patients undergoing interventions for asymptomatic CAS. Demographic data did not differ between groups. Patients with symptomatic CAS more frequently had prior TIA/stroke (>6 months remote to the current event), but less frequently had coronary artery disease or chronic kidney disease and were less likely to receive adequate medical management including antihypertensive agents, lipid-lowering agents, and anti-platelet therapy. On multivariate analysis, remote prior TIA/stroke and lack of anti-platelet therapy remained significant. Among symptomatic patients presenting with stroke, lack of anti-platelet therapy was associated with an overall larger area of parenchymal involvement. No difference was observed with single versus dual anti-platelet therapy. Furthermore, symptomatic patients were more likely to have ulcerated plaques (30.9% vs 18%, p < .001), and symptomatic patients with ulcerated plaques more frequently had less than 50% compared to moderate/severe CAS. Nine patients who presented with symptoms had mild CAS and underwent intervention. CONCLUSIONS: Symptomatic CAS was associated with a history of remote prior symptoms and lack of anti-platelet therapy at time of presentation. Furthermore, symptomatic patients not on anti-platelet agents were more likely to have a greater area of parenchymal involvement when presenting with stroke and symptomatic patients with ulcerated plaques were more likely to have mild CAS, suggesting the role of plaque instability in symptomatic presentation. These findings underscore the importance of appropriate medical management and adherence in all patients with CAS and perhaps a role for more frequent surveillance in those with potentially unstable plaque morphology.

Evolution of connectivity architecture in the Drosophila mushroom body.

Brain evolution has primarily been studied at the macroscopic level by comparing the relative size of homologous brain centers between species. How neuronal circuits change at the cellular level over evolutionary time remains largely unanswered. Here, using a phylogenetically informed framework, we compare the olfactory circuits of three closely related Drosophila species that differ in their chemical ecology: the generalists Drosophila melanogaster and Drosophila simulans and Drosophila sechellia that specializes on ripe noni fruit. We examine a central part of the olfactory circuit that, to our knowledge, has not been investigated in these species-the connections between projection neurons and the Kenyon cells of the mushroom body-and identify species-specific connectivity patterns. We found that neurons encoding food odors connect more frequently with Kenyon cells, giving rise to species-specific biases in connectivity. These species-specific connectivity differences reflect two distinct neuronal phenotypes: in the number of projection neurons or in the number of presynaptic boutons formed by individual projection neurons. Finally, behavioral analyses suggest that such increased connectivity enhances learning performance in an associative task. Our study shows how fine-grained aspects of connectivity architecture in an associative brain center can change during evolution to reflect the chemical ecology of a species.

Comparison of open and endovascular left subclavian artery revascularization for zone 2 thoracic endovascular aortic repair.

OBJECTIVE: In patients undergoing elective thoracic endovascular aortic repair (TEVAR) and left subclavian artery (LSA) coverage, routine preoperative LSA revascularization is recommended. However, in the current endovascular era, the optimal surgical approach is debated. We compared baseline characteristics, procedural details, and perioperative outcomes of patients undergoing open or endovascular LSA revascularization in the setting of TEVAR. METHODS: Adult patients undergoing TEVAR with zone 2 proximal landing and LSA revascularization between 2013-2023 were identified in the Vascular Quality Initiative. We excluded patients with traumatic aortic injury, aortic thrombus, or ruptured presentations, and stratified based on revascularization type (open vs. any endovascular). Open LSA revascularization included surgical bypass or transposition. Endovascular LSA revascularization included single-branch, fenestration, or parallel stent grafting. Primary outcomes were stroke, spinal cord ischemia, and perioperative mortality (Pearson's χ2-test). Multivariable logistic regression was used to evaluate associations between revascularization type and primary outcomes. Secondarily, we studied other in-hospital complications and 5-year mortality (Kaplan-Meier, multivariable Cox-regression). Sensitivity analysis was performed in patients undergoing concomitant LSA revascularization to TEVAR. RESULTS: Of 2,489 patients, 1,842 (74%) underwent open and 647 (26%) received endovascular LSA revascularization. Demographics and comorbidities were similar between open and endovascular cohorts. Compared with open, endovascular revascularization had shorter procedure times (median 135 vs. 174min, p<.001), longer fluoroscopy time (median 23 vs. 16min, p<.001), lower estimated blood loss (median 100 vs. 123ml, p<.001), and less preoperative spinal drain use (40% vs. 49%, p<.001). Patients undergoing endovascular revascularization were more likely to present urgently (24% vs. 19%) or emergently (7.4% vs. 3.4%) (p<.001). Compared with open, endovascular patients experienced lower stroke rates (2.6% vs. 4.8%, p=.026; aOR 0.50[95%C.I., 0.25-0.90]), but had comparable spinal cord ischemia (2.9% vs. 3.5%, p=.60; 0.64[0.31-1.22]) and perioperative mortality (3.1% vs. 3.3%, p=.94; 0.71[0.34-1.37]). Compared with open, endovascular LSA revascularization had lower rates of overall composite in-hospital complications (20% vs. 27%, p<.001; 0.64[0.49-0.83]) and shorter overall hospital stay (7 vs. 8 days, p<.001). After adjustment, 5-year mortality was similar among groups (aHR 0.85[0.64-1.13]). Sensitivity analysis supported the primary analysis with similar outcomes. CONCLUSIONS: In patients undergoing TEVAR starting in zone 2, endovascular LSA revascularization had lower rates of postoperative stroke and overall composite in-hospital complications, but similar spinal cord ischemia, perioperative and 5-year mortality rates compared with open LSA revascularization. Future comparative studies are needed to evaluate the mid- to long-term safety of endovascular LSA revascularization and assess differences between specific endovascular techniques.

The treatment of follicular lymphoma with CD19-directed chimeric antigen receptor T-cell therapy.

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Significant unmet need remains for patients with relapsed/refractory FL after ≥3 lines of prior therapy. While recent advancements have likely improved the survival of patients with FL, most patients will eventually relapse. The treatment of patients with FL after multiple relapses or those with refractory disease has historically led to lower overall response rates (ORR) and shorter progression-free survival (PFS) with each subsequent line of therapy. New treatments with high ORR and durable PFS are needed in this setting, particularly in patients that progress within 2 years of first line chemoimmunotherapy (POD24) and/or those refractory chemoimmunotherapy. Chimeric antigen receptor T-cell therapies targeting the B-cell antigen CD-19 have shown to be an efficacious treatment option for both heavily pretreated patients and/or patients with refractory FL, resulting in a high ORR and durable remissions.

Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells.

CD4+ regulatory T cells (Tregs) are key orchestrators of the immune system, fostering the establishment of protective immunity while preventing deleterious responses. Infancy and childhood are crucial periods of rapid immunologic development, but how Tregs mediate immune responses at these earliest timepoints of human life is poorly understood. In this study, we compare blood and tissue (tonsil) Tregs across pediatric and adult subjects to investigate age-related differences in Treg biology. We observed increased FOXP3 expression and proportions of Tregs in tonsil compared with paired blood samples in children. Within tonsil, early life Tregs accumulated in extrafollicular regions with cellular interactions biased toward CD8+ T cells. Tonsil Tregs in both children and adults expressed transcriptional profiles enriched for lineage defining signatures and canonical functionality compared with blood, suggesting tissue as the primary site of Treg activity. Early life tonsil Tregs transcriptional profiles were further defined by pathways associated with activation, proliferation, and polyfunctionality. Observed differences in pediatric tonsil Treg transcriptional signatures were associated with phenotypic differences, high proliferative capacity, and robust production of IL-10 compared with adult Tregs. These results identify tissue as a major driver of Treg identity, provide new insights into developmental differences in Treg biology across the human lifespan, and demonstrate unique functional properties of early life Tregs.

Outcomes of carotid revascularization stratified by procedure in eGFR<30 and dialysis patients.

OBJECTIVE: Renal failure is a predictor of adverse outcomes in carotid revascularization. There has been debate regarding the benefit of revascularization in patients with severe CKD or on dialysis. METHODS: VQI patients undergoing TCAR, tfCAS, or CEA between 2016 and 2023 with eGFR <30 ml/min/1.73m2 or on dialysis were included. Patients were divided into cohorts based on procedure. Additional analyses were performed for patients on dialysis only and by symptomatology. Primary outcomes were perioperative stroke/death/MI (SDM). Secondary outcomes included perioperative death, stroke, MI, CNI and stroke/death. Inverse probability of treatment weighting (IPW) was performed based on treatment assignment to TCAR, tfCAS, and CEA patients and adjusted for demographics, comorbidities, and pre-op symptoms. Chi-square and multivariable logistic regression analysis were used to evaluate the association of procedure with perioperative outcomes in the weighted cohort. Five-year survival was evaluated using Kaplan-Meier and weighted Cox regression. RESULTS: In the weighted cohort, 13,851 patients with eGFR of <30 (2,506 on dialysis) underwent TCAR (3,639, dialysis 704), tfCAS (1,975, 393) or CEA (8,237, 1,409) during the study period. Compared with TCAR, CEA had higher odds of stroke/death/MI (2.8% vs 3.6%, aOR 1.27 [1.00,1.61], p=.049), and MI (0.7% vs 1.5%, aOR 2.00 [1.31,3.05], p=.001)... Compared to TCAR, rates of SDM (2.8%vs5.8%), stroke (1.2%vs2.6%), death (0.9%vs2,4%)were all higher for tfCAS. In asymptomatic patients CEA patients had higher odds of MI (0.7% vs 1.3%, aOR 1.85[1.15, 2.97]p=.011) and CNI (0.3% vs 1.9%, aOR 7.23[3.28, 15.9] p<.001). Like the primary analysis, asymptomatic tfCAS patients demonstrated higher odds of death, and stroke/death. Symptomatic CEA patients demonstrated no difference in stroke, death or stroke/death. While tfCAS patients demonstrated higher odds of death, stroke, MI, stroke/death, and SDM. In both groups, 5-year survival was similar for TCAR and CEA (eGFR <30: 75.1% vs 74.2%, aHR1.06, p=.3) and lower for tfCAS (eGFR <30: 75.1% vs 70.4%, aHR1.44, p<.001) CONCLUSION: CEA and TCAR had similar odds of stroke and death and are both a reasonable choice in this population; however, TCAR may be better in patients with increased risk of MI. Additionally, tfCAS patients were more likely to have worse outcomes after weighting for symptom status. Finally, while patients with reduced eGFR have worse outcomes than their healthy peers, this analysis shows that the majority of patients survive long enough to benefit from the potential stroke risk reduction provided by all revascularization procedures.

A Comparison of COVID-19 Associated Hospitalization Rates Among Unvaccinated Versus Vaccinated Residents in Rhode Island, September 2022 to March 2024.

While the burden of COVID-19 in Rhode Island has diminished since 2020, Rhode Islanders' health continues to be severely impacted. We compared COVID-19 hospitalization rates among Rhode Islanders who did and did not receive the latest COVID-19 vaccination for the 2022-2023 and 2023-2024 COVID-19 seasons (November through March). Crude and age-adjusted rate ratios were calculated for each season comparing hospitalization rates of unvaccinated and vaccinated individuals. During the 2022-2023 season, individuals who were not vaccinated with the bivalent COVID-19 vaccine were 3.6 times (95% CI=2.8-4.6) more likely to be hospitalized for COVID-19 than individuals who received the vaccine, whereas during the 2023-2024 season, not receiving the updated vaccine was associated with a 2.4 times (95% CI=1.8-3.3) higher risk of hospitalization. The study provides the first assessment of the protection from hospitalization provided by COVID-19 vaccinations among Rhode Islanders and highlights the importance of continued vaccination for COVID-19.

Menopause and Estrogen Associations With Gut Barrier, Microbial Translocation, and Immune Activation Biomarkers in Women With and Without HIV.

OBJECTIVES: Estrogens may protect the gut barrier and reduce microbial translocation and immune activation, which are prevalent in HIV infection. We investigated relationships of the menopausal transition and estrogens with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV. DESIGN: Longitudinal and cross-sectional studies nested in the Women's Interagency HIV Study. METHODS: Intestinal fatty acid binding protein, lipopolysaccharide binding protein, and soluble CD14 (sCD14) levels were measured in serum from 77 women (43 with HIV) before, during, and after the menopausal transition (∼6 measures per woman over ∼13 years). A separate cross-sectional analysis was conducted among 72 postmenopausal women with HIV with these biomarkers and serum estrogens. RESULTS: Women in the longitudinal analysis were a median age of 43 years at baseline. In piecewise, linear, mixed-effects models with cutpoints 2 years before and after the final menstrual period to delineate the menopausal transition, sCD14 levels increased over time during the menopausal transition (Beta [95% CI]: 38 [12 to 64] ng/mL/yr, P = 0.004), followed by a decrease posttransition (-46 [-75 to -18], P = 0.001), with the piecewise model providing a better fit than a linear model (P = 0.0006). In stratified analyses, these results were only apparent in women with HIV. In cross-sectional analyses, among women with HIV, free estradiol inversely correlated with sCD14 levels (r = -0.26, P = 0.03). Lipopolysaccharide binding protein and intestinal fatty acid binding protein levels did not appear related to the menopausal transition and estrogen levels. CONCLUSIONS: Women with HIV may experience heightened innate immune activation during menopause, possibly related to the depletion of estrogens.

Proposed Increases in Government Authority Over Research Misconduct Proceedings.

This Viewpoint discusses changes proposed by the US Department of Health and Human Services' Office of Research Integrity that would shift control of research misconduct proceedings from institutional oversight to federal authority.

Real-world use of medical therapy in moderate asymptomatic carotid stenosis.

OBJECTIVE: Despite level 1 evidence demonstrating the benefit of carotid endarterectomy for the prevention of stroke in patients with severe asymptomatic carotid stenosis (ACS), there has been a trend toward recommending optimal medical therapy (OMT) alone. This recommendation has been promulgated based on the observation that modern advances in OMT reduce the overall stroke risk in the general population, but the success of this treatment strategy is dependent on patient and provider adherence. In current practice, patients with moderate ACS are nearly all treated with OMT alone. The objective of this study was to evaluate adherence to OMT in a cohort of patients with moderate ACS undergoing treatment with OMT alone. METHODS: Consecutive carotid duplex ultrasound examinations were reviewed for the years 2019 and 2020. Those with moderate (50%-69%) ACS based on Society for Vascular Surgery guidelines were included in the study. Patients were assessed for OMT at the time of the index duplex, the first follow-up visit, and at each subsequent follow-up visit until the end of the study. OMT was defined as abstinence from smoking, aspirin or other antiplatelet use, and statin or other lipid-lowering therapy. Patients were stratified based on their ability to achieve OMT, and each component was evaluated to identify shortfalls in therapy. RESULTS: A total of 323 duplex ultrasound examinations with moderate ACS in 255 patients were identified. Of the 255 patients, 143 (56.1%) were on OMT at the time of the first duplex; that number increased to 163 (63.9%) by the first follow-up visit and 175 (68.6%) by the completion of the study. There were 112 (43.9%) patients who were not on OMT at the time of the index duplex, 43 (38.4%) of whom achieved OMT over a median follow-up time of 2.7 years. By the end of follow-up, 86 (76.8%) were taking aspirin or another antiplatelet medication, 93 (83.0%) were on statin or other lipid-lowering therapy, and 74 (66.1%) were abstinent from smoking. Pre-duplex smoking was independently associated with failure to achieve OMT (hazard ratio: 0.452, P = .017). CONCLUSIONS: Among patients with moderate ACS who were not previously on OMT, the rate of OMT achievement is poor. Although advances in lipid management through statin therapy have been praised for their role in improving the effectiveness of OMT, smoking cessation represents an important target for improving uptake and as a result effectiveness of OMT.