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BACKGROUND: The objective of this study was to evaluate the efficacy of an in-person, small-group mammography video discussion (SMVD) intervention on mammography uptake among nonadherent Chinese American immigrant women. METHODS: Women (N = 956) were randomized into either an SMVD group, where Chinese-speaking community health workers (CHWs) used an effective, culturally appropriate video to discuss mammography, or a video-only group, which viewed the cultural video sent by mail. Outcomes were mammography uptake at 6 months and 21 months postintervention. RESULTS: Women in both groups increased mammography uptake, and an outcome analysis revealed no group differences (adjusted odds ratio [AOR], 1.18; 95% confidence interval [CI], .68-2.06). Overall, 61.2% of the SMVD group and 55.3% of the video-only group had at least one mammogram during the 21-month follow-up period. When considering attendance to the SMVD, SMVD attendees had higher mammography uptake than the video-only group (AOR, 1.51; 95% CI, 1.19-1.92), and SMVD nonattendees had lower mammography uptake than the video-only group (AOR, .33; 95% CI, .22-.50). CONCLUSIONS: Both intervention strategies were associated with increased mammography uptake. The authors observed that the increase in use was greater among women who participated in the SMVD session compared with those who viewed the cultural video only. Future research may explore a virtual SMVD intervention for higher session attendance and increased mammography uptake (ClinicalTrials.gov identifier NCT01292200).

AimTo evaluate the mechanosensitivity of muscle satellite cells (MuSCs) and fibro-adipogenic progenitors (FAPs) in cerebral palsy (CP) and the efficacy of the drug verteporfin in restoring cells' regenerative capacity.MethodMuscle biopsies were collected from six children with CP and six typically developing children. MuSCs and FAPs were isolated and plated on collagen-coated polyacrylamide gels at stiffnesses of 0.2 kPa, 8 kPa, and 25 kPa. Cells were treated with verteporfin to block mechanosensing or with dimethyl sulfoxide as a negative control. MuSC differentiation and FAP activation into myofibroblasts were measured using immunofluorescence staining.ResultsSurprisingly, MuSC differentiation was not affected by stiffness; however, stiff substrates resulted in large myonuclear clustering. Across all stiffnesses, MuSCs from children with CP had less differentiation than those of their typically developing counterparts. FAP activation into myofibroblasts was significantly higher in children with CP than their typically developing peers, but was not affected by stiffness. Verteporfin did not affect differentiation or activation in either cell population, but slightly decreased myonuclear clustering on stiff substrates.InterpretationCells from children with CP were less regenerative and more fibrotic compared to those of their typically developing counterparts, with MuSCs being sensitive to increases in stiffness. Therefore, the mechanosensitivity of MuSCs and FAPs may represent a new target to improve differentiation and activation in CP muscle.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies. AIMS: This study investigated memantines impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio and completed 36 weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and blood was collected for biomarker analysis. RESULTS: Of the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24-83 years, male-to-female ratio ~3:2). Fifty-two participants completed the study treatment with no significant differences in disease progression, biomarker changes (including neurofilament light chain [NfL]), or neuropsychiatric testing noted between the groups. Initial NfL values correlated with the rate of ALSFRS-R decline. DISCUSSION: In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.

ObjectivePatients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils.DesignIn this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with alcohol-use disorder (AUD; n=20) and AH (n=80) from a multicentre cohort (InTeam). To identify protein groups that are disproportionately represented, we conducted over-representation analysis using Reactome pathway analysis and Gene Ontology to determine the proteins with the most significant impact. A faecal biomarker and its prognostic effect were validated by ELISA in faecal samples from patients with AH (n=70), who were recruited in a second and independent multicentre cohort (AlcHepNet).ResultFaecal proteomic profiles were overall significantly different between controls, patients with AUD and AH (principal component analysis p=0.001, dissimilarity index calculated by the method of Bray-Curtis). Proteins that showed notable differences across all three groups and displayed a progressive increase in accordance with the severity of alcohol-associated liver disease were predominantly those located in neutrophil granules. Over-representation and Reactome analyses confirmed that differentially regulated proteins are part of granules in neutrophils and the neutrophil degranulation pathway. Myeloperoxidase (MPO), the marker protein of neutrophil granules, correlates with disease severity and predicts 60-day mortality. Using an independent validation cohort, we confirmed that faecal MPO levels can predict short-term survival at 60 days.ConclusionsWe found an increased abundance of faecal proteins linked to neutrophil degranulation in patients with AH, which is predictive of short-term survival and could serve as a prognostic non-invasive marker.

Gastric dilatation and volvulus (GDV) is a life-threatening emergency that requires urgent intervention. Radiographic features associated with 360-GDV in dogs have not been investigated. The aim of this retrospective observational study is to describe radiographic features and clinical variables in dogs affected with 360-GDV and to report agreement rates between different radiologists. We also report the sensitivity and specificity of radiographs to diagnose 360-GDV in dogs. Confirmed 360-GDV cases were retrieved, and the radiographic findings were compared with dogs presenting with gastric dilatation (GD) and 180-GDV. Images were reviewed and graded by three blinded board-certified radiologists. A total of 16 dogs with confirmed 360-GDV were identified. The median age was 10 years old (2-13 years). The sensitivity for detection of 360-GDV ranged between 43.7% and 50%, and the specificity between 84.6% and 92.1%. Interobserver agreement on final diagnosis was substantial (Kappa = 0.623; 0.487-0.760, 95% CI). The highest agreement rate was in cases of 180-GDV (87%), followed by the GD cases (72%) and 360-GDV (46%). Severe esophageal distension and absence of small intestinal dilation were the only radiographic features specifically associated with 360-GDV. A similar pyloric position was found between GD and 360-GDV. Additional radiographic variables that could help differentiate GD from 360-GDV include the degree of gastric distension and the peritoneal serosal contrast. Two cases with 360-GDV were misdiagnosed by the three radiologists as GD. In conclusion, radiographically, 360-GDV cases can reassemble GD and vice versa. Radiologists and clinicians should be aware of the low sensitivity of radiographs for the detection of 360-GDV.

OBJECTIVE: Peripheral nerves remain a challenging target for medical imaging, given their size, anatomical complexity, and structural heterogeneity. Quantitative ultrasound (QUS) applies a set of techniques to estimate tissue acoustic parameters independent of the imaging platform. Many useful medical and laboratory applications for QUS have been reported, but challenges remain for deployment in vivo, especially for heterogeneous tissues. Several phenomena introduce variability in attenuation estimates, which may influence the estimation of other QUS parameters. For example, estimating the backscatter coefficient (BSC) requires compensation for the attenuation of overlying tissues between the transducer and the underlying tissue of interest. The purpose of this study is to extend prior studies by investigating the efficacy of several analytical methods of estimating attenuation compensation on QUS outcomes in the human median nerve. METHODS: Median nerves were imaged at the volar wrist in vivo and beam-formed radiofrequency (RF) data were acquired. Six analytical approaches for attenuation compensation were compared: 1-2) attenuation estimated by applying spectral difference method (SDM) and spectral log difference method (SLDM) independently to regions of interest (ROIs) overlying the nerve and to the nerve ROI itself; 3-4) attenuation estimation by applying SDM and SLDM to ROIs overlying the nerve, and transferring these properties to the nerve ROI; and 5-6) methods that apply previously published values of tissue attenuation to the measured thickness of each overlying tissue. Mean between-subject estimates of BSC-related outcomes as well as within-subject variability of these outcomes were compared among the 6 methods. RESULTS: Compensating for attenuation using SLDM and values from the literature reduced variability in BSC-based outcomes, compared to SDM. Variability in attenuation coefficients contributes substantially to variability in backscatter measurements. CONCLUSION: This work has implications for the application of QUS to in vivo diagnostic assessments in peripheral nerves and possibly other heterogeneous tissues.

INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

BACKGROUND: Pain is common in patients with chronic liver disease. Our limited understanding of patterns and severity of pain in this population hinders the development of effective cirrhosis-specific pain management strategies. METHODS: Using cross-sectional data from the 2016-2021 National Health Interview Survey, we examined rates, severity, and functional limitations due to pain in respondents with liver disease (viral hepatitis, cirrhosis, and liver cancer), compared to the general population and those with other chronic conditions associated with pain (ie, arthritis, diabetes, and chronic kidney disease). Categorical and continuous variables were compared using χ2 and t test. Multivariable logistic regression was used to determine the predictors associated with pain and opioid use. RESULTS: Our liver disease cohort comprised 5267 participants (63% viral hepatitis, 49% cirrhosis, and 2% liver cancer). Participants with liver disease were more likely to report pain than those without liver disease (42% vs. 22%); they were also more likely to report severe pain (42% vs. 30%) and functional limitations by pain (28% vs. 13%) (p < 0.001 for all). On multivariable logistic regression, liver disease is an independent predictor of pain (OR: 2.31, 95% CI: 2.05-2.59, p < 0.001), even after adjustment for demographic factors. Liver disease respondents had similar rates of pain as those with diabetes (p = 0.8) and were more functionally limited by pain than those with arthritis (p < 0.001). Adjusted for demographic and pain-related factors, liver disease was also an independent predictor of chronic opioid use (OR: 1.47, 95% CI: 1.12-1.92, p = 0.0054). CONCLUSIONS: Liver disease independently increases the likelihood of experiencing widespread and debilitating pain. Clinicians should consider liver disease a painful condition, ensuring that they are frequently assessing and appropriately treating pain in all liver disease patients.

BackgroundAs people living with HIV (PWH) age, they face new challenges that can have a negative impact on their quality of life (QOL) and mental health.SettingThis study enrolled PWH at the end of life (EOL) who were actively engaged in cure-related research in Southern California, United States. EOL was defined as having a prognosis of 6 months or less to live. We examined the relationship between QOL, mental health, and research participation.MethodsStructured assessments were used to collect comprehensive data on QOL and mental health.ResultsFrom 2017 to 2023, 35 PWH in their final stages of life who were actively engaged in cure-related research were enrolled. Their median age was 62.7 years, and most were White or otherwise non-Hispanic/non-Latino (90.6%), and male (86.7%). Changes in QOL and the presence of neurologic and psychiatric conditions, with a focus on depression and anxiety, were the primary outcomes assessed in this study. Participants had stable QOL scores throughout the study. There was an inverse relationship between QOL and Beck Depression Inventory scores, with higher mean QOL scores being associated with lower mean Beck Depression Inventory scores ( P < 0.001).ConclusionsQOL remained stable among PWH who participate in cure-related research at EOL. The inverse relationship between QOL and depressive symptoms suggests that participation in cure-related research may improve QOL or reduce depressive symptoms in this population. Future interventions should look into ways to improve the well-being of PWH at EOL through research and customized mental health interventions.

BACKGROUND: Condylar fractures are a major cause of morbidity and mortality in Thoroughbred racehorses. Condylar fractures have a variety of fracture configurations that suggest there may be differences in aetiopathogenesis. OBJECTIVE: To determine if exercise history differs with condylar fracture location in a population of Thoroughbred racehorses. STUDY DESIGN: Retrospective analysis of clinical and exercise data. METHODS: Exercise history of Thoroughbred racehorses that had condylar fracture repair between 1 January 2018 and 28 February 2021 was compared between racehorses that had fractures located radiographically either within the parasagittal groove (PSG) or abaxial to the PSG (non-PSG). Age, sex, and last event (race, timed work) matched control groups were compared between the PSG and non-PSG groups. Additionally, exercise history variables of both groups were each compared with a group-specific control population, each consisting of three control racehorses of equivalent age and sex matched to each affected racehorse by last event (race or official timed work) before fracture. RESULTS: Eighty-two horses with 84 fractures (45 PSG, 39 non-PSG) met inclusion criteria. Age was not different between groups (PSG: 3.4 ± 1.3 years [mean ± SD], non-PSG: 3.7 ± 1.3, p = 0.3). Number of races (PSG: 5.3 ± 7.1, non-PSG: 11.4 ± 8.9, p

Parenting that is warm and supportive has been consistently linked to better emotion regulation in children, but less is known about this association in adolescents. Adolescence is thought to be an important period for emotion regulation development given that it coincides with the emergence of mental health issues. Respiratory sinus arrhythmia (RSA) is a measure of parasympathetic regulation linked to emotion and behavior regulation. Despite the well-documented links between parenting practices and emotion regulation, and between RSA and emotion regulation, few studies have focused on the association between positive parenting and adolescent RSA or included both mothers and fathers. The current study analyzed the influence of warm parenting throughout adolescence (ages 10-16) on basal RSA at age 17 in 229 Mexican-origin youths. Latent-growth curve models were used to analyze associations between maternal and paternal warmth and baseline RSA. Changes in maternal, but not paternal, warmth from age 10 to 16 were related to youths' basal RSA at age 17. Specifically, youths who perceived increasing (or less decreasing) maternal warmth across adolescence had higher basal RSA. This finding suggests that positive maternal parenting experiences during adolescence "get under the skin" to enhance parasympathetic functioning that supports youths' emotion regulation capacities.

OBJECTIVES: Mobile health (mHealth) regimens can improve health through the continuous monitoring of biometric parameters paired with appropriate interventions. However, adherence to monitoring tends to decay over time. Our randomized controlled trial sought to determine: (1) if a mobile app with gamification and financial incentives significantly increases adherence to mHealth monitoring in a population of heart failure patients; and (2) if activity data correlate with disease-specific symptoms. MATERIALS AND METHODS: We recruited individuals with heart failure into a prospective 180-day monitoring study with 3 arms. All 3 arms included monitoring with a connected weight scale and an activity tracker. The second arm included an additional mobile app with gamification, and the third arm included the mobile app and a financial incentive awarded based on adherence to mobile monitoring. RESULTS: We recruited 111 heart failure patients into the study. We found that the arm including the financial incentive led to significantly higher adherence to activity tracker (95% vs 72.2%, P = .01) and weight (87.5% vs 69.4%, P = .002) monitoring compared to the arm that included the monitoring devices alone. Furthermore, we found a significant correlation between daily steps and daily symptom severity. DISCUSSION AND CONCLUSION: Our findings indicate that mobile apps with added engagement features can be useful tools for improving adherence over time and may thus increase the impact of mHealth-driven interventions. Additionally, activity tracker data can provide passive monitoring of disease burden that may be used to predict future events.

OBJECTIVE: Hypertension is a major risk factor for dementia, but sustained blood pressure control is difficult to achieve. We evaluated whether inadequately controlled hypertension may contribute to excess dementia risk among people with HIV. DESIGN: A retrospective cohort study. METHODS: We studied demographically matched people with and without HIV between July 1, 2013, and December 31, 2021, who were at least 50 years old and had a hypertension diagnosis but no dementia diagnosis. Hypertension control was calculated using a disease management index (DMI), which captured degree and duration above the hypertension treatment goals of SBP less than 140 mmHg and DBP less than 90 mmHg. DMI values ranged from 0 to 100% (perfect control); hypertension was considered inadequately controlled if DMI was less than 80% (i.e., in control for

Gender norms have been posited to impact intimate partner violence (IPV), but there is scant evidence of the longitudinal association between community-level gender norms and IPV. Using longitudinal data on 3,965 married girls surveyed in India, we fitted mixed-effects ordinal and binary logistic regression models for physical IPV intensity and occurrence of sexual IPV. We found a 26% increase in the odds that women experience frequent physical IPV per one unit increase in greater community-level equitable gender norms. We did not find an association between community-level equitable gender norms and sexual IPV. Findings suggest that the relationship between gender norms and physical and sexual IPV differs, indicating the need for tailored interventions for different types of IPV.

BACKGROUND: Home-based primary care (HBPC) is an important care delivery model for high-need older adults. Currently, target patient populations vary across HBPC programs, hindering expansion and large-scale evaluation. OBJECTIVES: Develop and validate criteria that identify appropriate HBPC target populations. RESEARCH DESIGN: A modified Delphi process was used to achieve expert consensus on criteria for identifying HBPC target populations. All criteria were defined and validated using linked data from Medicare claims and the National Health and Aging Trends Study (NHATS) (cohort n=21,727). Construct validation involved assessing demographics and health outcomes/expenditures for selected criteria. SUBJECTS: Delphi panelists (n=29) represented diverse professional perspectives. Criteria were validated on community-dwelling Medicare beneficiaries (age ≥70) enrolled in NHATS. MEASURES: Criteria were selected via Delphi questionnaires. For construct validation, sociodemographic characteristics of Medicare beneficiaries were self-reported in NHATS, and annual health care expenditures and mortality were obtained via linked Medicare claims. RESULTS: Panelists proposed an algorithm of criteria for HBPC target populations that included indicators for serious illness, functional impairment, and social isolation. The algorithms Delphi-selected criteria applied to 16.8% of Medicare beneficiaries. These HBPC target populations had higher annual health care costs [Med (IQR): $10,851 (3316, 31,556) vs. $2830 (913, 9574)] and higher 12-month mortality [15% (95% CI: 14, 17) vs. 5% (95% CI: 4, 5)] compared with the total validation cohort. CONCLUSIONS: We developed and validated an algorithm to define target populations for HBPC, which suggests a need for increased HBPC availability. By enabling objective identification of unmet demands for HBPC access or resources, this algorithm can foster robust evaluation and equitable expansion of HBPC.

Fragile X syndrome (FXS) is a significant cause of intellectual disability and autism, while Fragile X Premutation -Associated Conditions (FXPAC) are a significant cause of morbidity and mortality globally. This study assessed the level of knowledge and perceptions about FXS and FXPAC among doctors in Nigeria. It was a web-based, cross-sectional study conducted among a cohort of doctors in Nigeria. Socio-demographic profile, knowledge of FXS, perceptions about FXS, knowledge of FXPAC, experience of doctors, and suggested ways of improving knowledge and management of FXS were obtained. Data were analyzed using STATA 16.0. Chi-square and Fishers exact tests of association were used to determine the association between variables, with the significance level set at p

BACKGROUND AND PURPOSE: Acute ischemic stroke due to anterior circulation large-vessel occlusion (AIS-LVO) remains a leading cause of disability despite successful reperfusion therapies. Prolonged venous transit (PVT) has emerged as a potential prognostic imaging biomarker in AIS-LVO. We aimed to investigate whether PVT is associated with a decreased likelihood of excellent functional outcome (modified Rankin Scale [mRS] score of 0-1 at 90 days) after successful reperfusion. METHODS: In our prospectively collected, retrospectively reviewed database, we analyzed data from 104 patients with AIS-LVO who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/2c/3) between September 2017 and September 2022. PVT was defined as a time to maximum (Tmax) of ≥10 s in the superior sagittal sinus and/or torcula on computed tomography perfusion (CTP) imaging. Patients were categorized into PVT-positive (PVT+) and PVT-negative (PVT-) groups. The primary outcome was excellent functional recovery at 90 days. RESULTS: Of the 104 patients, 30 (29%) were PVT+. Excellent functional outcome was achieved in 38 patients (37%). PVT+ patients had a significantly lower rate of excellent recovery compared to PVT- patients (11% vs. 39%; p

ObjectiveLittle is known about how the COVID-19 pandemic affected cancer screenings among American Indian people residing in California and Oklahoma, 2 states with the largest American Indian populations. We assessed rates and factors associated with cancer screenings among American Indian adults during the pandemic.MethodsFrom October 2020 through January 2021, we surveyed 767 American Indian adults residing in California and Oklahoma. We asked participants whether they had planned to obtain screenings for breast cancer, cervical cancer, and colorectal cancer (CRC) from March through December 2020 and whether screening was postponed because of COVID-19. We calculated adjusted odds ratios (AORs) for factors associated with reasons for planned and postponed cancer screening.ResultsAmong 395 participants eligible for breast cancer screening, 234 (59.2%) planned to obtain the screening, 127 (54.3%) of whom postponed it. Among 517 participants eligible for cervical cancer screening, 357 (69.1%) planned to obtain the screening, 115 (32.2%) of whom postponed it. Among 454 participants eligible for CRC screening, 282 (62.1%) planned to obtain CRC screening, 80 of whom (28.4%) postponed it. In multivariate analyses, women who lived with a child (vs did not) had lower odds of planning to obtain a breast cancer screening (AOR = 0.6; 95% CI, 0.3-1.0). Adherence to social distancing recommendations was associated with planning to have and postponement of cervical cancer screening (AOR = 7.3; 95% CI, 0.9-58.9). Participants who received (vs did not receive) social or financial support had higher odds of planning to have CRC screening (AOR = 2.0; 95% CI, 1.1-3.9).ConclusionThe COVID-19 pandemic impeded completion of cancer screenings among American Indian adults. Interventions are needed to increase the intent to receive evidence-based cancer screenings among eligible American Indian adults.

The current economic burden of cardiovascular (CV)-related hospitalizations grouped by diagnoses and procedures in the United States has not been well characterized. The objective was to identify current trends in CV-related hospitalizations, procedural utilization, and health care costs using the most recent 6 years of hospitalization data. A retrospective analysis of discharge data from the National Inpatient Sample database was conducted to determine trends in CV-related hospitalizations, costs, and procedures for each year from 2016 to the most recent available dataset, 2021. Total CV-related costs were adjusted to and reported in 2023 dollars. In 2021, there were 4,687,370 CV-related hospitalizations at a cost of $108 billion. Heart failure hospitalizations accounted for the highest costs at $18.5 billion, followed by non-ST-elevation myocardial infarction at $11.2 billion and stroke at $10.9 billion. Significant upward trends in costs from 2016 to 2021 were observed for heart failure, stroke, atrial fibrillation, ST-elevation myocardial infarction, chest pain, hypertensive emergency, ventricular tachycardia, aortic dissection, sudden cardiac death, pericarditis, supraventricular tachycardia, and pulmonary heart disease. Over the 6 observational years, total costs increased by over $10 billion, representing a 10% increase. However, the increases were not linear, as there was a significant increase of 6.5% from 2018 to 2019, then a decrease of over 7% from 2019 to 2020, followed by an increase of approximately 6% from 2020 to 2021. By 2030, total CV-related costs are projected to reach $131.3 billion. For all years, coronary procedures were the most performed, followed by extracorporeal membrane oxygenation, non-bypass peripheral vascular surgery, pacemaker placement, and coronary artery bypass graft surgery. Both transcatheter aortic valve replacement and MitraClip procedures demonstrated significant upward trends from 2016 to 2021. Overall, from the years 2016 to 2021, CV-related hospitalizations, costs, and procedures demonstrated upward trends. In conclusion, CV disease remains a high burden in the hospital setting with tremendous health care costs.

BackgroundThis study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL).MethodsPatients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified.Results177 patients underwent IOWL (N ​= ​85) or POWL (N ​= ​92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 ​% vs. 23.9 ​%, p ​= ​0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 ​% vs. 18.5 ​%, p ​= ​0.011). Presence of DCIS was associated with positive margins (p ​= ​0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 ​% CI 0.13-0.93).ConclusionsIn this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience.

BACKGROUND: We sought consensus among practising respiratory physicians on the prediction, identification and monitoring of progression in patients with fibrosing interstitial lung disease (ILD) using a modified Delphi process. METHODS: Following a literature review, statements on the prediction, identification and monitoring of progression of ILD were developed by a panel of physicians with specialist expertise. Practising respiratory physicians were sent a survey asking them to indicate their level of agreement with these statements on a binary scale or 7-point Likert scale (- 3 to 3), or to select answers from a list. Consensus was considered to be achieved if ≥ 70% of respondents selected the same answer, or, for responses on a Likert scale, the median score was ≤ -2 (disagree/not important) or ≥ 2 (agree/important) with an interquartile range ≤ 1. There were three rounds of the survey. RESULTS: Surveys 1, 2 and 3 were completed by 207, 131 and 94 physicians, respectively, between March 2022 and July 2023. Decline in forced vital capacity (FVC), decline in diffusing capacity of the lungs for carbon monoxide, and increased fibrosis on high-resolution computed tomography (HRCT) were ranked as the most important endpoints for determining progression. Consensus was reached that progression on HRCT or a decline in FVC ≥ 10% from baseline is sufficient to determine progression, and that small declines in multiple endpoints indicates progression. Consensus was reached that a histological pattern of usual interstitial pneumonia (UIP) is a risk factor for progression of ILD, but that a biopsy to look for a UIP pattern should not be performed solely for prognostic reasons. Consensus was not reached on the time period over which progression should be defined. There was consensus that appropriate management of ILD depends on the type of ILD, and that despite adequate management or despite usual management should be included in the definition of progression. CONCLUSIONS: This modified Delphi process provided consensus statements on the identification of ILD progression that were supported by a broad group of clinicians and may help to inform clinical practice until robust evidence-based guidelines are available.

BACKGROUND: The COVID-19 pandemic resulted in the rapid implementation of telemedicine for HIV care at federally qualified health centers (FQHCs) in the United States. We sought to understand use of telemedicine (telephone and video) at two FQHCs in Los Angeles, and the client attitudes towards and experiences with telemedicine as part of future HIV care. METHODS: We conducted surveys with 271 people living with HIV (PLHIV), with questions covering sociodemographic factors, telemedicine attitudes and experiences, technological literacy, and access to technological resources and privacy. Survey data were analyzed utilizing summary statistics, chi-square analyses, and Fishers exact test to understand associations between sociodemographic factors and telemedicine attitudes and experiences. RESULTS: Sixty percent of the sample had used any telemedicine and, of these, 93% utilized only telephone visits. Almost all respondents (95%, n = 257) had access to a functioning smartphone and self-rated their technological literacy as high. Most had consistent access to privacy (88%, n = 239), and those without privacy noted this as a barrier to the use of telemedicine. The main benefits of telemedicine (compared to in person) were savings of time and money, convenience, and ability to complete appointments as scheduled. Just over half of PLHIV said they would feel more comfortable discussing sensitive topics (e.g., substance use, relationship issues) in person than over telephone (60%, n = 164) or video (55%, n = 151). Despite limited experience with video telemedicine, half of all participants desired a mix of telephone and video visits as part of their future HIV care. CONCLUSIONS: During a mature phase of the COVID-19 pandemic, PLHIV in our study showed high satisfaction with telemedicine, largely conducted as telephone visits, and high interest in telemedicine visits as a component of their future HIV care. Future studies should explore barriers to implementing video telemedicine in FQHCs and determine telemedicines impact on clinical outcomes, including engagement and viral suppression.

Background: The Female Leadership Academy for Medical Excellence, members of the World Academic Council of Emergency Medicine, conducted this systematic review, which explores gender disparities in burnout among emergency physicians (EP) using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Burnout is a critical issue in healthcare, particularly in emergency medicine where high stress and demanding work environments prevail.Methods: Following PRISMA guidelines, we searched PubMed and Epistemonikos for studies using MBI-HSS to measure burnout in EPs. Inclusion criteria encompassed peer-reviewed, English-language articles reporting burnout by sex. Data extraction focused on proportions of burnout and its subcomponents, mean scores, and odds ratios, with quality assessed using Joanna Briggs Institute criteria.Results: We included 18 studies spanning 26,939 EPs from 10 countries. While overall burnout rates did not significantly differ between the sexes, the proportion of female EPs with high emotional exhaustion (EE) (69%) and low sense of personal accomplishment (PA) (45%) were significantly higher compared to males with high EE in 57% and low PA in 29%, respectively (P < 0.001 for both). Proportion with high depersonalization (DP) score was 44% in both male and female EPs. Mean scores revealed females experiencing higher mean EE (26.8 ± 15.7) scores vs males (25.4 ± 15.9) P < 0.001. Males had mean DP scores (8.6 ± 8.0) and mean PA scores (26.6 ± 12.7) compared to females with lower mean DP scores (7.4 ± 7.2) and higher PA scores (27.7 ± 11.9), respectively P < 0.001 for both. Odds ratios indicated varying risks, predominantly higher EE odds among females, varying from 0.72 to 2.3.Conclusion: This review underscores gender-specific manifestations of burnout among emergency physicians, with females more susceptible to emotional exhaustion and lower sense of personal accomplishment. Standardized reporting methods are crucial for future meta-analyses to refine gender-specific interventions combating burnout in emergency medicine. Targeted strategies addressing distinct manifestations of burnout are imperative to support the well-being and retention of EPs, fostering sustainable healthcare delivery.

BackgroundLeadership skills are essential for middle-level healthcare manager efficacy. Capacity-building efforts may attempt behavioural change by filling 'knowledge gaps' while neglecting a sustainable application of that knowledge. Sustainable application of that knowledge, or implementation know-how, must resonate with local cultural patterns. When it is neglected, root issues like unclear decision-making space and local authority to interpret policy during implementation remain unaddressed. Particularly in decentralized healthcare systems, the impact can appear in implementation challenges, subjective decision-making, poor teamwork, and an absence of disseminating best practices.ObjectivesThe SEARCH-IPT trial led a series of mini-collaborative meetings, which provided business leadership and management training for an intervention group of mid-level healthcare system managers in rural Eastern, East-Central, and Southwestern Uganda to see whether this would increase uptake of isoniazid-prevention therapy (IPT) for people living with HIV (PLHIV) in intervention districts. IPT is known to reduce active tuberculosis (TB), a leading cause of death among PLHIV, by 40-60%.MethodsWe performed a thematic analysis of six focus-group discussions from this intervention (held in May 2019, January 2020, September 2021) and 23 key informant interviews with control group participants (between February and August 2019 and September and December 2020).ResultsAnalysis revealed five implementation skill sets District Health Officers (DHOs) and District Tuberculosis and Leprosy Supervisors (DTLSs) deployed to achieve sustainable implementation and realize their decision-making space. The five practices were as follows: data-based decision-making, root-cause analysis, quality assurance, evidence-based empowerment, and sharing best practices with colleagues.ConclusionThese practices reached beyond outcome measures to address root problems around the DHO's range of authority and elicit buy-in from district health workers. For successful capacity building at the mid-manager level, focusing on core practices as part of competency is objectively implementable and measurable at the system level and does not rely on DHO self-assessments.

Shared clinical decision-making (SCDM) about HPV vaccination has been recommended for U.S. mid-adults aged 27-45 since 2019. To explore barriers and facilitators to HPV vaccination in this population, we conducted 14 virtual focus groups with 86 unvaccinated mid-adults (34 men and 52 women) in Californias medically underserved Inland Empire between September 2020 and January 2021. We systematically analyzed the focus group data using the rigorous and accelerated data reduction (RADaR) technique to identify key themes. Identified barriers included: lack of awareness, vaccine hesitancy, and perceived unaffordability (cited in 14 groups); lack of healthcare provider communication and insufficient time (13 groups); fear of moral judgment (12 groups); lack of motivation and information needs (10 groups); and lack of reliable transportation and foregone care during the COVID-19 pandemic (3 groups). Proposed facilitators included: tailored HPV vaccine information for mid-adults, cost mitigation, and improved vaccine accessibility (12 groups); healthcare provider-initiated conversations (6 groups); and vaccine reminders (4 groups). These findings highlight challenges to HPV vaccination among U.S. mid-adults eligible for SCDM and point to actionable strategies for improvement. Specifically, tailored educational interventions, decision-making tools for pharmacists, and integrating HPV vaccination into other healthcare encounters may enhance vaccination efforts in areas with limited primary care resources.

Aim: A radio-pathomic machine learning (ML) model has been developed to estimate tumor cell density, cytoplasm density (Cyt) and extracellular fluid density (ECF) from multimodal MR images and autopsy pathology. In this multicenter study, we implemented this model to test its ability to predict survival in patients with recurrent glioblastoma (rGBM) treated with chemotherapy.Methods: Pre- and post-contrast T1-weighted, FLAIR and ADC images were used to generate radio-pathomic maps for 51 patients with longitudinal pre- and post-treatment scans. Univariate and multivariate Cox regression analyses were used to test the influence of contrast-enhancing tumor volume, total cellularity, mean Cyt and mean ECF at baseline, immediately post-treatment and the pre- and post-treatment rate of change in volume and cellularity on overall survival (OS).Results: Smaller Cyt and larger ECF after treatment were significant predictors of OS, independent of tumor volume and other clinical prognostic factors (HR = 3.23 × 10-6, p

Uptake of COVID-19 vaccine booster doses is an important public health topic of study to prevent morbidity and mortality in underserved U.S. populations. However, limited research exists on COVID-19 vaccine booster use and willingness - including its associated factors - among Asian Americans (AA): the fastest growing racial group in the U.S. This study collected survey data from 447 AA adults from three large AA subgroups: Chinese, Korean, and Filipino. Data were collected as part of a community-driven county-wide needs assessment conducted in collaboration with AA community organizations in Riverside County, California. Data indicated that nearly 24% of AA participants received at least four doses of the COVID-19 vaccine, with 36% expressing definite willingness to receive future booster doses. Participants reported experiencing an average of 1.6 instances of racial discrimination across their lifetime. Ordered logistic regression and marginal effects analysis revealed ethnicity, education, racial discrimination, preexisting health conditions, and the number of prior COVID-19 vaccine doses received significantly predicted willingness to receive future vaccine doses. The study suggests that key social factors such as racial discrimination may play an important role in influencing public health efforts to promote vaccine uptake in diverse Asian American populations.

Dentists are well-positioned to discuss oral health issues related to Human Papillomavirus (HPV) and recommend the HPV vaccine to their patients, mainly because the HPV virus causes oropharyngeal cancers.. We assessed Los Angeles (LA) County dentists opinions on discussing HPV-related oral health issues and recommending the HPV vaccine to their patients. We tested if opinions differed between dentists whose primary patient population was only adults versus children and adults. We mailed a 19-item survey to 2000 randomly sampled LA County dentists for this cross-sectional study. The primary outcome variable was a summary opinion score of 7 opinion statements. We ran descriptive, bivariate comparisons and adjusted linear regression models. Overall, 261 dentists completed the survey. A majority (58.5%) worried they would lose patients if they recommended the vaccine; 49% thought dentists were not appropriate to educate, counsel, or advise on HPV-related issues; 42% were concerned about the safety of the vaccine; and 40% did not feel comfortable recommending the vaccine. The mean summary opinion score was 21.4 ± 5.4 for the total sample. Regression analysis showed no differences in opinions between dentists whose primary patient population was only adults versus children and adults (Coefficient = 0.146, p = 0.83). Overall, the responding dentists were not very favorable about discussing oral health-related HPV issues and recommending the HPV vaccine to their patients. Additionally, the overall opinions were similar between dentists whose primary patient population was only adults versus children and adults.

Substantial evidence indicates that medical mistrust, resulting from experiences with discrimination and marginalisation, is a determinant of health disparities in minority populations. However, this research is largely limited to the US and other industrialised countries. To broaden our understanding of the role of medical mistrust on health-care decision making, we conducted a study on healthcare experiences and perceptions in a rural, underserved indigenous community in northwest Namibia (n = 86). Mixing semi-structured interview questions with the medical mistrust index (MMI), we aim to determine the relevance of the MMI in a non-industrialised population and compare index scores with reports of healthcare experiences. We find that medical mistrust is a salient concept in this community, mapping onto negative healthcare experiences and perceptions of discrimination. Reported healthcare experiences indicate that perceived incompetence, maltreatment and discrimination drive mistrust of medical personnel. However, reporting of recent healthcare experiences are generally positive. Our results indicate that the concept of medical mistrust can be usefully applied to communities in the Global South. These populations, like minority communities in the US, translate experiences of discrimination and marginalisation into medical mistrust. Understanding these processes can help address health disparities and aid in effective public health outreach in underserved populations.

As medical schools move to integrate the Core Entrustable Professional Activities for Entering Residency (EPAs) into curricula and address the transition from student to resident, residency preparatory courses have become more prevalent. The authors developed an experiential learning EPA-based capstone course for assessment to determine impact on learner self-assessed ratings of readiness for residency and acquisition of medical knowledge. All fourth-year students from the classes of 2018-2020 completed a required course in the spring for assessment of multiple EPAs, including managing core complaints, performing basic procedures, obtaining informed consent, and providing patient handoffs. Learners selected between three specialty-based parallel tracks - adult medicine, surgery, or pediatrics. Students completed a retrospective pre-post questionnaire to provide self-assessed ratings of residency preparedness and comfort in performing EPAs. Finally, the authors studied the impact of the course on knowledge acquisition by comparing student performance in the adult medicine track on multiple choice pre- and post-tests. Four hundred and eighty-one students were eligible for the study and 452 (94%) completed the questionnaire. For all three tracks, there was a statistically significant change in learner self-assessed ratings of preparedness for residency from pre- to post-course (moderately or very prepared: adult medicine 61.4% to 88.6% [p-value < 0.001]; surgery 56.8% to 81.1% [p-value < 0.001]; pediatrics 32.6% to 83.7% [p-value 0.02]). A similar change was noted in all tracks in learner self-assessed ratings of comfort from pre- to post-course for all studied EPAs. Of the 203 students who participated in the adult medicine track from 2019-2020, 200 (99%) completed both the pre- and post-test knowledge assessments. The mean performance improved from 65.0% to 77.5% (p-value < 0.001). An experiential capstone course for the assessment of EPAs can be effective to improve learner self-assessed ratings of readiness for residency training and acquisition of medical knowledge.

INTRODUCTION: Student-run free clinics (SRFCs) offer medical students a unique opportunity to develop their clinical, diagnostic, and social skills while providing care to medically underserved communities. This study aims to evaluate the value of SRFC involvement on students self-reported confidence in various clinical domains and satisfaction with their medical education. METHODS: We conducted a single-center retrospective pre-post assessment at an urban academic institution among second- to fourth-year medical students. We administered a 25-item questionnaire capturing the scope of clinic involvement and assessing self-reported confidence in multiple clinical domains following a one-year-long participation in student-run free clinics. RESULTS: Fifty-six students completed the survey. Participation in SRFCs significantly increased self-reported confidence in patient history-taking (p

PurposeThis study sought to understand family functioning surrounding weight in Mexican American women with obesity.MethodsSemi-structured in-depth interviews were conducted with mothers and adult daughters (N = 116).ResultsThematic analysis identified five themes. 1) The communication process drives perception of supportive messages. Messages perceived as non-supportive consist of directives as interventions, confirmation of faults, and critical compliments whereas supportive consist of compliments, encouragement, empathetic listening, and disclosure. 2) Acculturation differences interfere with intergenerational alliance. Differences involve dissonance in communication, behavioural expectations, and weight-related practices. 3) Maladaptive conflict responses contribute to relational strain. These responses include avoidance, withdrawal, and defensiveness. 4) Role transformations alter the generational hierarchical relationship. Daughters serve as role models, caregivers, or collaborators. 5) Low communal coping heightens psychological distress. It does so by challenging family roles, increasing social isolation, and compromising social support.ConclusionObesity interventions for Mexican American women may benefit from targeting relational skills to improve family functioning.

The insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.

AimTo assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery.Materials and methodsA decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results.ResultsIn this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan.LimitationsThere are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided.ConclusionThis analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

BackgroundThere is limited systematic information available about the perspectives of participants enrolled in intensive combination HIV cure-related trials inclusive of an extended analytical treatment interruption (ATI).ObjectiveTo assess and understand experiences of people with HIV involved in a combination HIV cure-related trial with an extended ATI.MethodsThe trial included five interventions and was followed by an ATI lasting up to 52 wk. From 2022 - 2023, we conducted in-depth interviews with study participants following their extended ATIs. Interviews were audio-recorded, transcribed, and analyzed via conventional thematic analysis.ResultsWe interviewed seven participants. The majority were male, White, and non-Hispanic, with a median age of 37 years. Trust in the research team, scientific altruism and hope of becoming a post-intervention controller were key motivators for joining the trial. Interviewees reported being satisfied with their decision to participate in the trial and the extended ATI. Most recounted feelings of worry related to viral rebound during the ATI. Participants reported both defeat and relief with ART restart. Four faced challenges with protecting partners from HIV during their ATI, such as trying to find out if their partner(s) were using pre-exposure prophylaxis.ConclusionsOur findings demonstrate potential improvements for future ATI trial participant experiences, such as more robust resources for psychosocial support and partner protections. Dedicating greater effort to understanding participant ATI experiences can inform the design of future participant-centered HIV cure trial protocols.

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Bile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

Glioblastoma is immunologically cold and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma and our secondary endpoint of PFS-6 was 19.5% (95% CI: 9.29-41.2%) for the pooled neoadjuvant cohorts. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.

Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. We did not observe significant changes in either biochemical parameters or levels of circulating markers of inflammation across the entire cohort. However, paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance of Weizmannia, a kombucha-enriched probiotic and several SCFA producing taxa to be overrepresented in consumers at the end of the intervention. Collectively, in our healthy cohort consuming a Western diet, a short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters, which may be attributed to relatively small number of participants and the extensive inter-participant variability.

Playing three-dimensional (3D) video games enhances stereo acuity (i.e., the precision of stereopsis) in young adults with normal vision Here we asked whether the improvement in stereoacuity was the result of a reduced disparity pedestal, as indicated by a decreased subjective depth bias (i.e., the accuracy of stereopsis). Twenty-one healthy young participants with normal vision and limited previous video game experience, none had played 3D video games, played first-person-shooter action stereoscopic 3D video games for a total of 40 h. Depth detection performance was measured using random dot stereograms before and after the video game intervention. We found that playing stereoscopic 3D video games boosts the precision, but not the accuracy of depth perception, suggesting that the enhanced stereoacuity did not result from reducing the effects of a disparity pedestal. These types of video games have potential therapeutic applications for improving stereo vision in patients with binocular vision anomalies.

Preserving the ability to vividly recall emotionally rich experiences contributes to quality of life in older adulthood. While prior works suggest that moderate-intensity physical activity (MPA) may bolster memory, it is unclear whether this extends to emotionally salient memories consolidated during sleep. In the current study, older adults (mean age = 72.3 ± 5.8) completed an overnight polysomnography assessment with emotional memory tested before and after sleep and a self-report questionnaire assessing habitual PA. Results show that better negative emotional memory consolidation was associated with the frequency and duration of MPA. Statistically replacing 30 min of lower-intensity activity with MPA was associated with better negative emotional memory consolidation. MPA may enhance sleep-dependent consolidation of negative memories in older adults, with modest increases in MPA yielding significant consolidation benefits. Findings may guide interventions and inform public health recommendations by demonstrating that substituting even short durations of low-intensity activity for MPA could produce significant cognitive gains in older adulthood.

Meal sorting in mosquitoes is a phenomenon whereby ingested blood and sugar meals are directed to different destinations in the alimentary canal. We undertake a systematic analysis and show that entry of blood in the midgut is influenced by blood components, temperature, and feeding mode, while sugar solutions are directed to the crop in a dose-dependent manner. Sweet and nutritive sugars, like sucrose and maltose, enter the crop more efficiently compared to non-sweet or non-nutritive sugars. Additionally, the robustness of meal sorting declines with mosquito age and is compromised in mutants of candidate thermoreceptors. Proper blood meal sorting is crucial for optimal egg production, as disruption of this process by adding sucrose results in reduced fecundity. Furthermore, certain amino acids essential for vitellogenesis are preferentially directed to the midgut. Our findings provide new insights into the meal sorting mechanism, with implications for mosquito reproduction and vectorial capacity.

Background and aimsVideo games are a common form of entertainment in adolescents, which may result in gaming habits characterized by impairment to reward-related decision-making. The aim of the current study was to investigate the relationship between reward processing and symptoms of gaming addiction in adolescents.MethodsData from three consecutive follow-up years (years 2, 3 and 4) of the Adolescent Brain Cognitive Development (ABCD) Study were analyzed (n = 6,143, total observations = 12,745, mean age at year-2 = 12 years). Participants completed the Video Game Addiction Questionnaire (VGAQ) at each visit. Discrete stages of reward processing were measured at the year-2 visit using the Monetary Incentive Delay task while the participant completed a functional magnetic resonance imaging (fMRI) scan. Bayesian hierarchical linear models were employed to examine the longitudinal association between reward processing in regions of interest at year-2 and VGAQ scores over time.ResultsLower activation in the bilateral caudate during the anticipation of a large reward (β = -0.87, 95% CI: -1.68, -0.07) was associated with greater VGAQ scores over time. This implies that for each one-unit increase in brain activity in the caudate, there was an associated 0.87-point decrease in symptoms of gaming addiction as measured by the VGAQ. No association was found between reward feedback and VGAQ scores.Discussion and conclusionsThe findings suggest that abnormal reward processing in the caudate nucleus is associated with symptoms of gaming addiction in adolescents. These results provide a clearer understanding of the brain mechanisms involved in gaming addiction, which could inform future preventive and therapeutic strategies.

Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4+ T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL. Compared with non-responders, responding patients have more circulating CD4+ naïve and central memory T cells and B cells, as well as more diverse CD4+ T cell and B cell receptor repertoires. Importantly, a population of circulating and tumor-infiltrating IL1β+ monocytes/macrophages is detectable in patients with cHL but not healthy donors, and a proinflammatory, tumor-promoting signature of these circulating IL1β+ monocytes is associated with resistance to PD-1 blockade in cHL. Altogether, our findings reveal extensive immune rewiring and complementary roles of CD4+ T cells, B cells and IL1β+ monocytes in the response to PD-1 blockade and suggest that these features can be captured with a peripheral blood test.

BACKGROUND: The 313-variant polygenic risk score (PRS313) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed. METHODS: We explored the distribution of PRS313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction. RESULTS: The mean PRS313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment. CONCLUSIONS: Our results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories.

INTRODUCTION: Down Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition causing insomnia, catatonia, encephalopathy, and obsessive-compulsive behavior in otherwise healthy individuals with Down syndrome (DS). Smaller cohorts have identified heterogenous diagnostic abnormalities which have predicted immunotherapy responsiveness although pattern analysis in a large cohort has never been performed. METHODS: A multi-center, retrospective study of individuals with DSRD was performed. Individuals met international consensus criteria for DRSD and were aged 10-30 years. Clinical, demographic, and diagnostic data was extracted for all individuals. Serum studies were compared to a group of individuals with DS only. RESULTS: A total of 164 individuals with DSRD were identified. Individuals with DSRD were more likely to have a positive antinuclear antibody, low complement 3, abnormal cytokines, and elevated ferritin levels. In a minority of individuals, EEG (30%), MRI (33%) and cerebrospinal fluid (CSF) (21%) were abnormal. Individuals with CSF abnormalities demonstrated greater disease severity at diagnosis on the BFCRS and NPI-Q (p = 0.02 and p

Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD). A four-class machine-learning algorithm was trained using age and nine sleep biomarkers from patients with clinically-diagnosed manifest and prodromal NDDs, including Alzheimers disease dementia (AD = 27), Lewy body dementia (LBD = 18), and isolated REM sleep behavior disorder (iRBD = 15), as well as a control group (CG = 58). The algorithm was validated in a total of 381 recordings, which included the training data set plus an additional AD = 10, iRBD = 18, Parkinson disease without dementia (PD = 29), mild cognitive impairment (MCI = 78) and CG = 128. Test-retest consistency was then assessed in LBD = 10, AD = 9, and CG = 46. The agreement between the NDD profiles and their respective clinical diagnoses exceeded 75% for the AD, LBD, and CG, and improved when NDD participants classified Likely Normal with NDD indications consistent with their clinical diagnosis were considered. Profiles for iRBD, PD and MCI participants were consistent with the heterogeneity of disease severities, with the majority of overt disagreements explained by normal sleep characterization in 27% of iRBD, 21% of PD, and 26% of MCI participants. For test-retest assignments, the same or similar NDD profiles were obtained for 88% of LBD, 86% in AD, and 98% of CG participants. The potential utility for NDD subtyping based on sleep biomarkers demonstrates promise and requires further prospective development and validation in larger NDD cohorts.

BACKGROUND: The use of medical abortion using either a combination of mifepristone and misoprostol, or misoprostol alone has contributed to increased safety and decreased mortality and morbidity. The availability of quality medical abortion medicines is an essential component in the provision of quality abortion care. Understanding the factors that influence the availability of medical abortion medicines is important to help in-country policymakers, program planners, and providers improve availability and use of medical abortion. METHODS: Using a national assessment protocol and an availability framework, we assessed the availability of medical abortion medicines across five elements (Registration & Quality Assurance, Policy & Financing, Procurement & Distribution, Provider Knowledge, and End-user Knowledge) in eight countries: Botswana, Burkina Faso, Central African Republic, Democratic Republic of the Congo, Eswatini, Lesotho, Namibia and Uganda between November 2020 and November 2021. The assessment included an online desk review and virtual or telephone-based key informant interviews. RESULTS: Registration of medical abortion medicines-misoprostol or co-packaged mifepristone and misoprostol products (combi-pack)-was established in all countries, except the Central African Republic. In Lesotho and Eswatini, the national regulatory agency is still in development and importation of Cytotec™ misoprostol is permitted for off-label use in obstetrics/gynecology. Misoprostol was included in all countries essential medicines lists, except Botswana. Burkina Faso and Democratic Republic of the Congo also include mifepristone on their essential medicines list and medical abortion regimens in national abortion care service and delivery guidelines. Additionally, guidelines clarified health worker roles in the provision of abortion care specific to the legal context of each country and permitted task-shifting of abortion service provision. Where guidelines did not exist, medical abortion medicines and their use were not well integrated into the public health care system. Community awareness activities on abortion rights and services have been limited in scope across the countries assessed, however, end-users awareness of misoprostol as a medical abortion medicine was reported. CONCLUSION: The national landscape assessments identified several cross-cutting opportunities to improve availability of medical abortion medicines, including importing quality-assured medical abortion medicines; developing nationally approved abortion service and delivery guidelines that optimize healthcare worker roles; and expanding communication strategies to reach end-users and pharmacists.

Microinfarcts and microhemorrhages are characteristic lesions of cerebrovascular disease. Although multiple studies have been published, there is no one universal standard criteria for the neuropathological assessment of cerebrovascular disease. In this study, we propose a novel application of machine learning in the automated screening of microinfarcts and microhemorrhages. Utilizing whole slide images (WSIs) from postmortem human brain samples, we adapted a patch-based pipeline with convolutional neural networks. Our cohort consisted of 22 cases from the University of California Davis Alzheimer's Disease Research Center brain bank with hematoxylin and eosin-stained formalin-fixed, paraffin-embedded sections across 3 anatomical areas: frontal, parietal, and occipital lobes (40 WSIs with microinfarcts and/or microhemorrhages, 26 without). We propose a multiple field-of-view prediction step to mitigate false positives. We report screening performance (ie, the ability to distinguish microinfarct/microhemorrhage-positive from microinfarct/microhemorrhage-negative WSIs), and detection performance (ie, the ability to localize the affected regions within a WSI). Our proposed approach improved detection precision and screening accuracy by reducing false positives thereby achieving 100% screening accuracy. Although this sample size is small, this pipeline provides a proof-of-concept for high efficacy in screening for characteristic brain changes of cerebrovascular disease to aid in screening of microinfarcts/microhemorrhages at the WSI level.