Search

BackgroundThe Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12.MethodsThis study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD).Primary resultsAt baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine,

Individually, the COVID-19 and HIV pandemics have differentially impacted minoritized groups due to the role of social determinants of health (SDoH) in the U.S. Little is known how the collision of these two pandemics may have exacerbated adverse health outcomes. We evaluated county-level SDoH and associations with hospitalization after a COVID-19 diagnosis among people with (PWH) and without HIV (PWOH) by racial/ethnic groups. We used the U.S. National COVID Cohort Collaborative (January 2020-November 2023), a nationally-sampled electronic health record repository, to identify adults who were diagnosed with COVID-19 with HIV (n = 22,491) and without HIV (n = 2,220,660). We aggregated SDoH measures at the county-level and categorized racial/ethnic groups as Non-Hispanic (NH) White, NH-Black, Hispanic/Latinx, NH-Asian and Pacific Islander (AAPI), and NH-American Indian or Alaskan Native (AIAN). To estimate associations of county-level SDoH with hospitalization after a COVID-19 diagnosis, we used multilevel, multivariable logistic regressions, calculating adjusted relative risks (aRR) with 95% confidence intervals (95% CI). COVID-19 related hospitalization occurred among 11% of PWH and 7% of PWOH, with the highest proportion among NH-Black PWH (15%). In evaluating county-level SDoH among PWH, we found higher average household size was associated with lower risk of COVID-19 related hospitalization across racial/ethnic groups. Higher mean commute time (aRR: 1.76; 95% CI 1.10-2.62) and higher proportion of adults without health insurance (aRR: 1.40; 95% CI 1.04-1.84) was associated with a higher risk of COVID-19 hospitalization among NH-Black PWH, however, NH-Black PWOH did not demonstrate these associations. Differences by race and ethnicity exist in associations of adverse county-level SDoH with COVID-19 outcomes among people with and without HIV in the U.S., (© 2024. The Author(s).)

There is a group of beta (β)-thalassemia trait 'carriers' (with heterozygous mutations) who should be asymptomatic with minor abnormalities in their hematological parameters, but experience more severe disease manifestations than predicted based solely on their β-globin genotype. This review focuses on literature describing trans-acting genetic modifiers outside of the α- and β-globin gene clusters that could cause this phenomenon. These genetic modifiers are categorized into: mutations affecting the quantity of alpha-globin products, non-globin mutations affecting erythropoiesis, membranopathies, enzymopathies and erythrocyte-independent modifiers of complications relating to β-thalassemia. Although some genetic determinants seem to correlate more directly with β-thalassemia trait severity, such as mutations in SUPT5H, PIEZO1 and hereditary elliptocytosis, the difficulties of linking the contribution of other modulating factors are elucidated in this review. Targeted next generation sequencing of hemolytic anemias can be helpful but also raises another quandary in interpreting variants of uncertain significance. The accrual of knowledge, along with the increased availability of genetic testing for genetic modifiers has considerable potential for clinical applications such as genetic counselling, decision-making for clinical interventions and prognostication, and perhaps generating new therapeutic targets., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: SC is a paid independent contractor of the International Association for Premenstrual Disorders (IAPMD). All other authors are unpaid members of IAPMD's clinical advisory board and report no financial relationships with commercial interests. JLG receives salary support through a Tier 2 Canadian Institutes of Health (CIHR) Canada Research Chair.

Background: As higher acuity procedures continue to move from hospital-based operating rooms (HORs) to free-standing ambulatory surgery centers (ASCs), concerns for patient safety remain high. We conducted a contemporary, descriptive analysis of anesthesia-related liability closed claims to understand risks to patient safety in the free-standing ASC setting, compared to HORs., Methods: Free-standing ASC and HOR closed claims between 2015 and 2022 from The Doctors Company that involved an anesthesia provider responsible for the claim were included. We compared the coded data of 212 free-standing ASC claims with 268 HOR claims in terms of severity of injury, major injuries, allegations, comorbidities, contributing factors, and financial value of the claim., Results: Free-standing ASC claims accounted for almost half of all anesthesia-related cases (44%, 212 of 480). Claims with high severity of injury were less frequent in free-standing ASCs (22%) compared to HORs (34%; P = .004). The most common types of injuries in both free-standing ASCs and HORs were dental injury (17% vs 17%) and nerve damage (14% vs 11%). No difference in frequency was noted for types of injuries between claims from free-standing ASCs versus HORs--except that burns appeared more frequently in free-standing ASC claims than in HORs (6% vs 2%; P = .015). Claims with alleged improper management of anesthesia occurred less frequently among free-standing ASC claims than HOR claims (17% vs 29%; P = .01), as well as positioning-related injury (3% vs 8%; P = .025). No difference was seen in frequency of claims regarding alleged improper performance of anesthesia procedures between free-standing ASCs and HORs (25% vs 19%; P = .072). Technical performance of procedures (ie, intubation and nerve block) was the most common contributing factor among free-standing ASC (74%) and HOR (74%) claims. Free-standing ASC claims also had a higher frequency of communication issues between provider and patient/family versus HOR claims (20% vs 10%; P = .004). Most claims were not associated with major comorbidities; however, cardiovascular disease was less prevalent in free-standing ASC claims versus HOR claims (3% vs 11%; P = .002). The mean ± standard deviation total of expenses and payments was lower among free-standing ASC claims ($167,000 ± $295,000) than HOR claims ($332,000 ± $775,000; P = .002)., Conclusions: This analysis of medical malpractice claims may indicate higher-than-expected patient and procedural complexity in free-standing ASCs, presenting patient safety concerns and opportunities for improvement. Ambulatory anesthesia practices should consider improving safety culture and communication with families while ensuring that providers have up-to-date training and resources to safely perform routine anesthesia procedures., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Background: The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin-releasing factor (CRF) has been previously documented. Here, we provide a comprehensive analysis of their identity and functional role in shaping reward learning., Methods: Our multidisciplinary approach included fluorescent in situ hybridization (n = ≥3 mice), tract tracing (n = 5 mice), ex vivo electrophysiology (n = ≥30 cells), in vivo calcium imaging with fiber photometry (n = ≥4 mice), and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (n = ≥4 mice). Behaviors used were instrumental learning, sucrose preference, and spontaneous exploration in an open field., Results: We showed that the vast majority of NAc CRF-containing neurons are spiny projection neurons (SPNs) comprising dopamine D 1 -, D 2 -, or D 1 /D 2 -containing SPNs that primarily project and connect to the ventral pallidum and to a lesser extent the ventral midbrain. As a population, they display mature and immature SPN firing properties. We demonstrated that NAc CRF-containing neurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning and at the same time facilitates flexibility in the face of changing contingencies., Conclusions: CRF release from this sparse population of SPNs is critical for reward learning under normal conditions., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Postoperative Delirium (POD) is the most common complication following surgery among older adults, and has been consistently associated with increased mortality and morbidity, cognitive decline, and loss of independence, as well as markedly increased health-care costs. The development of new tools to identify individuals at high risk for POD could guide clinical decision-making and enable targeted interventions to potentially decrease delirium incidence and POD-related complications. In this study, we used machine learning techniques to evaluate whether baseline (pre-operative) cognitive function and resting-state electroencephalography could be used to identify patients at risk for POD. Pre-operative resting-state EEGs and the Montreal Cognitive Assessment (MoCA) were collected from 85 patients (age = 73 ± 6.4 years) undergoing elective surgery, 12 of whom subsequently developed POD. The model with the highest f1-score for predicting delirium, a linear-discriminant analysis (LDA) model incorporating MoCA scores and occipital alpha-band EEG features, was subsequently validated in an independent, prospective cohort of 51 older adults (age ≥ 60) undergoing elective surgery, 6 of whom developed POD. The LDA-based model, with a total of 7 features, was able to predict POD with area under the receiver operating characteristic curve, specificity and accuracy all >90%, and sensitivity > 80%, in the validation cohort. Notably, models incorporating both resting-state EEG and MoCA scores outperformed those including either EEG or MoCA alone. While requiring prospective validation in larger cohorts, these results suggest that prediction of POD with high accuracy may be feasible in clinical settings using simple and widely available clinical tools.

Background: Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural effects after TMS remains unclear. TMS paired with electroencephalography (TMS-EEG) can causally probe these neural effects. Nonetheless, variability in single pulse TMS-evoked potentials (TEPs) across dlPFC subregions, and potential artifact induced by muscle activation, necessitate detailed mapping for accurate treatment monitoring., Objective: To characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and specifically that conditions with larger muscle artifact may exhibit lower observed EL-TEPs due to over-rejection during preprocessing. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach., Methods: In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses., Results: Stimulation location significantly influenced observed EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%., Significance: EL-TEPs can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols., Competing Interests: Declaration of interest CJK holds equity in Alto Neuroscience, Inc. All other authors have nothing to disclose., (Copyright © 2024 International Federation of Clinical Neurophysiology. All rights reserved.)

Background: The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) has been previously documented. Here we provide a comprehensive analysis of their identity and functional role in shaping reward learning., Methods: To do this, we took a multidisciplinary approach that included florescent in situ hybridization (N mice ≥ 3), tract tracing (N mice = 5), ex vivo electrophysiology (N cells ≥ 30), in vivo calcium imaging with fiber photometry (N mice ≥ 4) and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (N mice ≥ 4). Behaviors used were instrumental learning, sucrose preference and spontaneous exploration in an open field., Results: Here we show that the vast majority of NAc CRF-containing (NAc CRF ) neurons are spiny projection neurons (SPNs) comprised of dopamine D1-, D2- or D1/D2-containing SPNs that primarily project and connect to the ventral pallidum and to a lesser extent the ventral midbrain. As a population, they display mature and immature SPN firing properties. We demonstrate that NAc CRF neurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning, and at the same time facilitates flexibility in the face of changing contingencies., Conclusion: We conclude that CRF release from this sparse population of SPNs is critical for reward learning under normal conditions.

Black undergraduates face threats to healthy weight and body image (i.e., bodily well-being). Having a strong racial/ethnic identity can promote health during emerging adulthood. However, less is known about the intersections of racial/ethnic and religious identities on the bodily well-being of Black college-attending emerging adults, despite evidence to indicate that aspects of religiosity are also associated with health. We use quantitative data from 767 Black college-attending emerging adults in the Multi-University Study of Identity and Culture to examine the independent contributions of racial/ethnic and religious identity for bodily health, and test a potential interaction between racial/ethnic and religious identity on bodily health outcomes. Results from a multivariate linear regression model indicate that Black college-attending emerging adults with both high religious identity and high racial/ethnic identity exploration had higher body mass index and less positive body image. Findings suggest ways to strengthen the development of culturally appropriate public health prevention and intervention efforts that target body image and weight for Black college-attending emerging adults. IMPACT STATEMENT: Black college-attending emerging adults face challenges to their health, particularly threats to healthy weight and body image during this period of psychosocial transitions. The developmental process of navigating racial/ethnic and religious identities during this time raises challenges and opportunities for health promotion for this population. Yet, research that explores the role of these identities remains scarce. We found that Black college-attending emerging adults had higher body mass index and more negative body image when they reported more racial/ethnic identity exploration coupled with higher religious identities. Results shed light on the complex ways that navigating both racial/ethnic and religious identities may put some Black college-attending emerging adults at greater health risk. Health education and promotion practice focused on improving Black emerging adult health in college contexts should ensure that behavioral interventions are appropriately nuanced and situated in these populations' developmental and cultural considerations., (© 2023. W. Montague Cobb-NMA Health Institute.)

Introduction: Antiretroviral therapy (ART) and tuberculosis preventive treatment (TPT) both prevent tuberculosis (TB) disease and deaths among people living with HIV. Differentiated care models, including community-based care, can increase the uptake of ART and TPT to prevent TB in settings with a high burden of HIV-associated TB, particularly among men., Methods: We developed a gender-stratified dynamic model of TB and HIV transmission and disease progression among 100,000 adults ages 15-59 in KwaZulu-Natal, South Africa. We drew model parameters from a community-based ART initiation and resupply trial in sub-Saharan Africa (Delivery Optimization for Antiretroviral Therapy, DO ART) and other scientific literature. We simulated the impacts of community-based ART and TPT care programmes during 2018-2027, assuming that community-based ART and TPT care were scaled up to similar levels as in the DO ART trial (i.e. ART coverage increasing from 49% to 82% among men and from 69% to 83% among women) and sustained for 10 years. We projected the number of TB cases, deaths and disability-adjusted life years (DALYs) averted relative to standard, clinic-based care. We calculated programme costs and incremental cost-effectiveness ratios from the provider perspective., Results: If community-based ART care could be implemented with similar effectiveness to the DO ART trial, increased ART coverage could reduce TB incidence by 27.0% (range 21.3%-34.1%) and TB mortality by 34.6% (range 24.8%-42.2%) after 10 years. Increasing both ART and TPT uptake through community-based ART with TPT care could reduce TB incidence by 29.7% (range 23.9%-36.0%) and TB mortality by 36.0% (range 26.9%-43.8%). Community-based ART with TPT care reduced gender disparities in TB mortality rates, with a projected 54 more deaths annually among men than women (range 11-103) after 10 years of community-based care versus 109 (range 41-182) in standard care. Over 10 years, the mean cost per DALY averted by community-based ART with TPT care was $846 USD (range $709-$1012)., Conclusions: By substantially increasing coverage of ART and TPT, community-based care for people living with HIV could reduce TB incidence and mortality in settings with high burdens of HIV-associated TB and reduce TB gender disparities., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: A minority of naturally cycling individuals experience clinically significant affective changes across the menstrual cycle. However, few studies have examined cognitive and behavioral constructs that may maintain or worsen these changes. Several small studies link rumination with premenstrual negative affect, with authors concluding that a tendency to ruminate amplifies and perpetuates hormone-sensitive affective symptoms. Replication in larger samples is needed to confirm the validity of rumination as a treatment target., Method: 190 cycling individuals ( M = 30.82 years; 61.1% Caucasian) were recruited for moderate perceived stress, a risk factor for cyclical symptoms. They completed the Rumination Response Scale at baseline, then reported daily affective and physical symptoms across 1-6 cycles. Multilevel growth models tested trait rumination as a predictor of baseline levels, luteal increases, and follicular decreases in symptoms., Results: The degree of affective cyclicity was normally distributed across a substantial range, supporting feasibility of hypothesis tests and validating the concept of dimensional hormone sensitivity. Contrary to prediction, higher brooding did not predict levels or cyclical changes of any symptom. In a subsample selected for luteal increases in negative affect, brooding predicted higher baseline negative affect but still did not predict affective cyclicity., Conclusions: An individual's trait-like propensity to engage in rumination may not be a valid treatment target in premenstrual mood disorders. State-like changes in rumination should still be further explored, and well-powered prospective studies should explore other cognitive and behavioral factors to inform development of targeted psychological treatments for patients with cyclical affective symptoms.

Objective: We currently lack a robust noninvasive method to measure prefrontal excitability in humans. Concurrent TMS and EEG in the prefrontal cortex is usually confounded by artifacts. Here we asked if real-time optimization could reduce artifacts and enhance a TMS-EEG measure of left prefrontal excitability., Methods: This closed-loop optimization procedure adjusts left dlPFC TMS coil location, angle, and intensity in real-time based on the EEG response to TMS. Our outcome measure was the left prefrontal early (20-60 ms) and local TMS-evoked potential (EL-TEP)., Results: In 18 healthy participants, this optimization of coil angle and brain target significantly reduced artifacts by 63% and, when combined with an increase in intensity, increased EL-TEP magnitude by 75% compared to a non-optimized approach., Conclusions: Real-time optimization of TMS parameters during dlPFC stimulation can enhance the EL-TEP., Significance: Enhancing our ability to measure prefrontal excitability is important for monitoring pathological states and treatment response., Competing Interests: Declaration of Interest. CJK holds equity in Alto Neuroscience, Inc and is a consultant for Flow Neuroscience. All other authors have nothing to disclose.

Introduction: In military training settings, stress can improve focus and motivation fostering effective learning. However, high perceived stress can be debilitating resulting in poor learning and clinical errors. Multiple studies have focused on medical residency stress; but there has been minimal focus on dental residents and even less on the impact of the unique stressors from the COVID-19 pandemic. The objectives of this study were to determine the impact of the COVID-19 pandemic on perceived stress of residents in a military dental residency training program and explore the association among perceived stress and anxiety, depression, sleep quality, and social support., Materials and Methods: Dental residents (N = 20) at the Naval Postgraduate Dental School participated in this study. Residents were assessed via self-report measures quarterly from March 2020 through June 2021. The assessment included measures of anxiety (GAD-7), depression (PHQ-9), perceived stress (PSS), fatigue (FSI), and social support (DUKE-SSQ)., Results: Before the pandemic shutdown, 60% of participants reported high perceived stress. These residents reported an initial decrease in symptoms of anxiety, depression, and fatigue compared to residents reporting low pre-pandemic perceived stress but returned to baseline levels post-shutdown. Additionally, the high stress participants reported lower social support., Conclusions: Based on pre-pandemic perceived stress, participants responded differently to the impact of the pandemic shutdown. The low baseline stress participants may have a more robust sense of grit and resilience. These findings suggest that postgraduate dental training programs should integrate coping skills training opportunities, especially for residents reporting high perceived stress before residency., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Leveraging the National COVID-19 Cohort Collaborative (N3C), a nationally sampled electronic health records repository, we explored associations between individual-level social determinants of health (SDoH) and COVID-19-related hospitalizations among racialized minority people with human immunodeficiency virus (HIV) (PWH), who have been historically adversely affected by SDoH., Methods: We retrospectively studied PWH and people without HIV (PWoH) using N3C data from January 2020 to November 2023. We evaluated SDoH variables across three domains in the Healthy People 2030 framework: (1) healthcare access, (2) economic stability, and (3) social cohesion with our primary outcome, COVID-19-related hospitalization. We conducted hierarchically nested additive and adjusted mixed-effects logistic regression models, stratifying by HIV status and race/ethnicity groups, accounting for age, sex, comorbidities, and data partners., Results: Our analytic sample included 280,441 individuals from 24 data partner sites, where 3,291 (1.17%) were PWH, with racialized minority PWH having higher proportions of adverse SDoH exposures than racialized minority PWoH. COVID-19-related hospitalizations occurred in 11.23% of all individuals (9.17% among PWH, 11.26% among PWoH). In our initial additive modeling, we observed that all three SDoH domains were significantly associated with hospitalizations, even with progressive adjustments (adjusted odds ratios [aOR] range 1.36-1.97). Subsequently, our HIV-stratified analyses indicated economic instability was associated with hospitalization in both PWH and PWoH (aOR range 1.35-1.48). Lastly, our fully adjusted, race/ethnicity-stratified analysis, indicated access to healthcare issues was associated with hospitalization across various racialized groups (aOR range 1.36-2.00)., Conclusion: Our study underscores the importance of assessing individual-level SDoH variables to unravel the complex interplay of these factors for racialized minority groups., Competing Interests: All authors declare no conflicts of interest., (© The Author(s) 2024.)

Previous work assessing the effect of additive noise on the postural control system has found a positive effect of additive white noise on postural dynamics. This study covers two separate experiments that were run sequentially to better understand how the structure of the additive noise signal affects postural dynamics, while also furthering our knowledge of how the intensity of auditory stimulation of noise may elicit this phenomenon. Across the two experiments, we introduced three auditory noise stimulations of varying structure (white, pink, and brown noise). Experiment 1 presented the stimuli at 35 dB while Experiment 2 was presented at 75 dB. Our findings demonstrate a decrease in variability of the postural control system regardless of the structure of the noise signal presented, but only for high intensity auditory stimulation., (© 2024. The Author(s).)

Household-based tuberculosis (TB) contact evaluation may be an efficient strategy to reach people who could benefit from oral pre-exposure prophylaxis (PrEP) because of the epidemiological links between HIV and TB. This study estimated the number of HIV serodifferent couples in TB-affected households and potential HIV acquisitions averted through their PrEP use in 4 TB-HIV high-burden countries. We conducted a model-based analysis set in Ethiopia, Kenya, South Africa, and Uganda using parameters from population-based household surveys, systematic literature review and meta-analyses, and estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We parameterized the nonlinear relationship between the proportion of serodifferent couples among people living with HIV and population-level HIV prevalence using Markov chain Monte Carlo methods. We integrated all parameters in a mathematical model and propagated uncertainty using a Monte Carlo approach. We estimated the HIV prevalence among adults aged 15-49 living in TB-affected households to be higher than in the general population in all 4 countries. The proportion of serodifferent couples among all couples in TB-affected households was also higher than in the general population (South Africa: 20.7% vs. 15.7%, Kenya: 15.7% vs. 5.7%, Uganda: 14.5% vs. 6.0%, Ethiopia: 4.1% vs. 0.8%). We estimated that up to 1,799 (95% UI: 1,256-2,341) HIV acquisitions in South Africa could be prevented annually by PrEP use in serodifferent couples in TB-affected households, 918 (95% UI: 409-1,450) in Kenya, 686 (95% UI: 505-871) in Uganda, and 408 (95% UI: 298-522) in Ethiopia. As couples in TB-affected households are more likely to be serodifferent than couples in the general population, offering PrEP during household TB contact evaluation may prevent a substantial number of HIV acquisitions., Competing Interests: RVB reports support from the US National Institutes of Health and the Bill and Melinda Gates Foundation. Regeneron Pharmaceuticals covered the cost of abstract and manuscript writing outside the submitted work. RVB serves on a Gilead Sciences Data Monitoring Committee (DMC) for which she receives an honorarium. JMR reports research funds paid to her institution from Merck and Gilead Sciences outside of this work. The remaining authors declare no competing interests., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Identifying spatial variation in TB burden can help national TB programs effectively allocate resources to reach and treat all people with TB. However, data limitations pose challenges for subnational TB burden estimation., Methods: We developed a small-area modeling approach using geo-positioned prevalence survey data, case notifications, and geospatial covariates to simultaneously estimate spatial variation in TB incidence and case notification completeness across districts in Uganda from 2016-2019. TB incidence was estimated using 1) cluster-level data from the national 2014-2015 TB prevalence survey transformed to incidence, and 2) case notifications adjusted for geospatial covariates of health system access. The case notification completeness surface was fit jointly using observed case notifications and estimated incidence., Results: Estimated pulmonary TB incidence among adults varied >10-fold across Ugandan districts in 2019. Case detection increased nationwide from 2016 to 2019, and the number of districts with case detection rates >70% quadrupled. District-level estimates of TB incidence were five times more precise than a model using TB prevalence survey data alone., Conclusion: A joint spatial modeling approach provides useful insights for TB program operation, outlining areas where TB incidence estimates are highest and health programs should concentrate their efforts. This approach can be applied in many countries with high TB burden., (© 2024 The Authors.)

Background: Black young adult women (ages 18-35) are at disproportionate risk for obesity and emotional eating. Emotional eating interventions target psychological flexibility, such as reducing experiential avoidance and increasing acceptance of food-related thoughts. Yet Black women face gendered racism, and some endorse roles that reduce psychological flexibility, such as the superwoman schema role. Culturally centered stress and coping has often been overlooked, leading to an incomplete understanding of processes that engender emotional eating and the implications for appropriate and effective interventions for Black young adult women., Purpose: We investigated direct and indirect pathways of associations between stress from gendered racial microaggressions to emotional eating through the endorsement of superwoman schema and two aspects of psychological flexibility., Methods: Black young adult women (N = 504; Mage = 24.72; 75.2% African American; 98.4% cisgender) participated in an online survey wherein they reported demographics, stress from gendered racial microaggressions, superwoman schema, experiential avoidance, acceptance of food-related thoughts, and emotional eating. Path analysis was conducted to examine direct and indirect effects., Results: Results provided evidence for indirect associations between more stress from gendered racial microaggressions and more emotional eating. More stress was associated with greater endorsement of the superwoman schema which was associated with more experiential avoidance and less acceptance of food-related thoughts, which were each associated with more emotional eating., Conclusions: Endorsement of superwoman schema and concomitant avoidance and less acceptance may be one way that gendered racial stress propels emotional eating. Future research could test intervention components that disrupt this path., (© Society of Behavioral Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We currently lack a reliable method to probe cortical excitability noninvasively from the human dorsolateral prefrontal cortex (dlPFC). We recently found that the strength of early and local dlPFC transcranial magnetic stimulation (TMS)-evoked potentials (EL-TEPs) varied widely across dlPFC subregions. Despite these differences in response amplitude, reliability at each target is unknown. Here we quantified within-session reliability of dlPFC EL-TEPs after TMS to six left dlPFC subregions in 15 healthy subjects. We evaluated reliability (concordance correlation coefficient [CCC]) across targets, time windows, quantification methods, regions of interest, sensor- vs. source-space, and number of trials. On average, the medial target was most reliable (CCC = 0.78) and the most anterior target was least reliable (CCC = 0.24). However, all targets except the most anterior were reliable (CCC > 0.7) using at least one combination of the analytical parameters tested. Longer (20 to 60 ms) and later (30 to 60 ms) windows increased reliability compared to earlier and shorter windows. Reliable EL-TEPs (CCC up to 0.86) were observed using only 25 TMS trials at a medial dlPFC target. Overall, medial dlPFC targeting, wider windows, and peak-to-peak quantification improved reliability. With careful selection of target and analytic parameters, highly reliable EL-TEPs can be extracted from the dlPFC after only a small number of trials., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mitochondria are thought to have become incorporated within the eukaryotic cell approximately 2 billion years ago and play a role in a variety of cellular processes, such as energy production, calcium buffering and homeostasis, steroid synthesis, cell growth, and apoptosis, as well as inflammation and ROS production. Considering that mitochondria are involved in a multitude of cellular processes, mitochondrial dysfunction has been shown to play a role within several age-related diseases, including cancers, diabetes (type 2), and neurodegenerative diseases, although the underlying mechanisms are not entirely understood. The significant increase in lifespan and increased incidence of age-related diseases over recent decades has confirmed the necessity to understand the mechanisms by which mitochondrial dysfunction impacts the process of aging and age-related diseases. In this review, we will offer a brief overview of mitochondria, along with structure and function of this important organelle. We will then discuss the cause and consequence of mitochondrial dysfunction in the aging process, with a particular focus on its role in inflammation, cognitive decline, and neurodegenerative diseases, such as Huntington's disease, Parkinson's disease, and Alzheimer's disease. We will offer insight into therapies and interventions currently used to preserve or restore mitochondrial functioning during aging and neurodegeneration.

Mitochondrial dysfunction has been implicated in aging and age-related disorders. Disturbed-protein homeostasis and clearance of damaged proteins have also been linked to aging, as well as to neurodegenerative diseases, cancers, and metabolic disorders. However, since mitochondrial oxidative phosphorylation, ubiquitin-proteasome, and autophagy-lysosome systems are tightly interdependent, it is not understood whether the facets observed in aging are the causes or consequences of one or all of these failed processes. We therefore used prematurely aging mtDNA-mutator mice and normally aging wild-type littermates to elucidate whether mitochondrial dysfunction per se is sufficient to impair cellular protein homeostasis similarly to that which is observed in aging. We found that both mitochondrial dysfunction and normal aging affect the ubiquitin-proteasome system in a tissue-dependent manner, whereas only normal aging markedly impairs the autophagy-lysosome system. Thus, our data show that the proteostasis network control in the prematurely aging mtDNA-mutator mouse differs in certain aspects from that found in normal aging. Taken together, our findings suggest that severe mitochondrial dysfunction drives an aging phenotype associated with the impairment of certain components of the protein homeostasis machinery, while others, such as the autophagy-lysosome system, are not affected or only minimally affected. Taken together, this shows that aging is a multifactorial process resulting from alterations of several integrated biological processes; thus, manipulating one process at the time might not be sufficient to fully recapitulate all changes associated with normal aging.

The Deterioration Index (DI) is an automatic early warning system that utilizes a machine learning algorithm integrated into the electronic health record and was implemented to improve risk stratification of inpatients. Our pilot implementation showed superior diagnostic accuracy than standard care. A score >60 had a specificity of 88.5% and a sensitivity of 59.8% (PPV 0.1758, NPP 0.9817). However, acceptance in the clinical workflow was divided; nurses preferred standard care, while providers found it helpful.

Awareness of racial health care inequities is one prerequisite to eliminating them. Although extant research has described awareness of racial health care inequities in the United States, the health impacts of such awareness on communities that are most impacted by these inequities remains unknown. Therefore, we examined associations between awareness of Black-White racial health care inequities and self-rated health for Black and White adults in the United States. We used survey data from non-Hispanic Black and White participants ( N = 6,449) who responded to the national American Health Values Survey (2015-2016) to test associations between awareness of Black-White inequities in health care and self-rated health. Accurate awareness of health care inequities was associated with 47% higher odds of poorer self-rated health for Black individuals. Inaccurate awareness was associated with 36% higher odds of poorer self-rated health for White individuals. Accurate awareness may be adaptive, yet place an additional burden on Black individuals. Inaccurate awareness may harm White individuals' health. Health care system changes and alleviation of racism-related stress may be preventive supports for the health of Black individuals. Accurate awareness should be a goal for White individuals, not only to prevent health risks, but to also facilitate structural change for racial equity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: Cross-sectional and preliminary longitudinal findings suggest that cyclical ovarian hormone fluctuations influence acute suicide risk. The authors provide the first analyses in females with suicidality to investigate which daily symptoms covary with suicidal ideation and planning thoughts, the role of the menstrual cycle in daily symptom variation, how daily fluctuations in symptoms mediate the menstrual cycle-suicidality relationship, and how these associations vary across individuals., Methods: Naturally cycling psychiatric outpatients (N=119) with past-month suicidal ideation provided daily ratings of psychiatric symptoms (depression, hopelessness, anxiety, feeling overwhelmed, agitation, anhedonia, worthlessness, rejection sensitivity, anger, perceived burdensomeness, and interpersonal conflict), suicidal ideation, and suicidal planning across at least one menstrual cycle. Symptom ratings were decomposed into trait (person-centered mean) and state (daily person-centered mean deviation) components. Five cycle phases were identified in relation to menses onset and ovulation (surge in urine luteinizing hormone level). Hypotheses were tested in multilevel structural equation models., Results: Nearly all psychiatric symptoms covaried with fluctuations in daily suicidal ideation, and a limited set of symptoms (depression, hopelessness, rejection sensitivity, and perceived burdensomeness) predicted within-person increases in suicidal planning. Many patients demonstrated perimenstrual worsening of psychiatric symptoms, suicidal ideation, and suicidal planning. Depressive symptoms (depression, hopelessness, perceived burdensomeness, and anhedonia) were the most robust statistical mediators predicting perimenstrual exacerbation of suicidality., Conclusions: Research on the menstrual cycle and suicide has been limited historically by small, cross-sectional samples. This study provides the first evidence that measuring day-to-day correlates of suicidality in a large transdiagnostic sample of females with suicidal ideation can contribute to understanding the pathways by which the menstrual cycle influences acute suicide risk., Competing Interests: The authors report no financial relationships with commercial interests.

How does a train of TMS pulses modify neural activity in humans? Despite adoption of repetitive TMS (rTMS) for the treatment of neuropsychiatric disorders, we still do not understand how rTMS changes the human brain. This limited understanding stems in part from a lack of methods for noninvasively measuring the neural effects of a single TMS train-a fundamental building block of treatment-as well as the cumulative effects of consecutive TMS trains. Gaining this understanding would provide foundational knowledge to guide the next generation of treatments. Here, to overcome this limitation, we developed methods to noninvasively measure causal and acute changes in cortical excitability and evaluated this neural response to single and sequential TMS trains. In 16 healthy adults, standard 10 Hz trains were applied to the dorsolateral prefrontal cortex in a randomized, sham-controlled, event-related design and changes were assessed based on the TMS-evoked potential (TEP), a measure of cortical excitability. We hypothesized that single TMS trains would induce changes in the local TEP amplitude and that those changes would accumulate across sequential trains, but primary analyses did not indicate evidence in support of either of these hypotheses. Exploratory analyses demonstrated non-local neural changes in sensor and source space and local neural changes in phase and source space. Together these results suggest that single and sequential TMS trains may not be sufficient to modulate local cortical excitability indexed by typical TEP amplitude metrics but may cause neural changes that can be detected outside the stimulation area or using phase or source space metrics. This work should be contextualized as methods development for the monitoring of transient noninvasive neural changes during rTMS and contributes to a growing understanding of the neural effects of rTMS., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The current review highlights the available research related to cannabis and indicators of physical health in a variety of domains. Various studies have found associations between cannabis use with pulmonary, cardiovascular, gastrointestinal, and endocrine function as well as body mass index and sleep. At this time, more research is needed to understand the influence of cannabis use on physical health, particularly among adolescent samples., (Published by Elsevier Inc.)

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation designed to induce changes of cortical excitability that outlast the period of TBS application. In this study, we explored the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) versus sham TBS stimulation, applied to the left primary motor cortex, on modulation of resting state electroencephalography (rsEEG) power. We first conducted hypothesis-driven region-of-interest (ROI) analyses examining changes in alpha (8-12 Hz) and beta (13-21 Hz) bands over the left and right motor cortex. Additionally, we performed data-driven whole-brain analyses across a wide range of frequencies (1-50 Hz) and all electrodes. Finally, we assessed the reliability of TBS effects across two sessions approximately 1 month apart. None of the protocols produced significant group-level effects in the ROI. Whole-brain analysis revealed that cTBS significantly enhanced relative power between 19 and 43 Hz over multiple sites in both hemispheres. However, these results were not reliable across visits. There were no significant differences between EEG modulation by active and sham TBS protocols. Between-visit reliability of TBS-induced neuromodulatory effects was generally low-to-moderate. We discuss confounding factors and potential approaches for improving the reliability of TBS-induced rsEEG modulation., (© 2023. The Author(s).)

Introduction: The COVID-19 pandemic continues with highly contagious variants and waning immunity. As the virus keeps evolving to be more infectious and immune evasive, some question whether the COVID-19 pandemic can be managed through sustainable public health measures., Methods: We developed an agent-based simulation to explore the impact of COVID-19 mutations, periodic vaccinations, and nonpharmaceutical interventions on reducing COVID-19 deaths. The model is calibrated to the greater Seattle area by observing local epidemic data. We perform scenario analyses on viral mutations that change infectiousness, disease severity, and immune evasiveness from previous infections and vaccination every 6 months. The simulation is run until the end of year 2023., Results: Variants with increased infectivity or increased immune evasion dominate previous strains. With enhanced immune protection from a pancoronavirus vaccine, the most optimistic periodic vaccination rate reduces average total deaths by 44.6% compared with the most pessimistic periodic vaccination rate. A strict threshold nonpharmaceutical intervention policy reduces average total deaths by 71.3% compared with an open society, whereas a moderate nonpharmaceutical intervention policy results in a 33.6% reduction., Conclusions: Our findings highlight the potential benefits of pancoronavirus vaccines that offer enhanced and longer-lasting immunity. We emphasize the crucial role of nonpharmaceutical interventions in reducing COVID-19 deaths regardless of virus mutation scenarios. Owing to highly immune evasive and contagious SARS-CoV-2 variants, most scenarios in this study fail to reduce the mortality of COVID-19 to the level of influenza and pneumonia. However, our findings indicate that periodic vaccinations and a threshold nonpharmaceutical intervention policy may succeed in achieving this goal. This indicates the need for caution and vigilance in managing a continuing COVID-19 epidemic., (© 2023 The Author(s).)

Visual stimuli that deviate from the current context elicit augmented responses in the primary visual cortex (V1). These heightened responses, known as "deviance detection," require local inhibition in the V1 and top-down input from the anterior cingulate area (ACa). Here, we investigated the mechanisms by which the ACa and V1 interact to support deviance detection. Local field potential recordings in mice during an oddball paradigm showed that ACa-V1 synchrony peaks in the theta/alpha band (≈10 Hz). Two-photon imaging in the V1 revealed that mainly pyramidal neurons exhibited deviance detection, while contextually redundant stimuli increased vasoactive intestinal peptide (VIP)-positive interneuron (VIP) activity and decreased somatostatin-positive interneuron (SST) activity. Optogenetic drive of ACa-V1 inputs at 10 Hz activated V1-VIPs but inhibited V1-SSTs, mirroring the dynamics present during the oddball paradigm. Chemogenetic inhibition of V1-VIPs disrupted Aca-V1 synchrony and deviance detection in the V1. These results outline temporal and interneuron-specific mechanisms of top-down modulation that support visual context processing., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Context modulates how information is processed in the mammalian brain. For example, brain responses are amplified to contextually unusual stimuli. This phenomenon, known as "deviance detection," 1 , 2 is well documented in early, primary sensory cortex, where large responses are generated to simple stimuli that deviate from their context in low-order properties, such as line orientation, size, or pitch. 2 , 3 , 4 , 5 However, the extent to which neural deviance detection manifests (1) in broader cortical networks and (2) to simple versus complex stimuli, which deviate only in their higher-order, multisensory properties, is not known. Consistent with a predictive processing framework, 6 , 7 we hypothesized that deviance detection manifests in a hierarchical manner across cortical networks, 8 , 9 emerging later and further downstream when stimulus deviance is complex. To test this, we examined brain responses of awake mice to simple unisensory deviants (e.g., visual line gratings, deviating from context in their orientation alone) versus complex multisensory deviants (i.e., audiovisual pairs, deviating from context only in their audiovisual pairing but not visual or auditory content alone). We find that mouse parietal associative area-a higher cortical region-displays robust multisensory deviance detection. In contrast, primary visual cortex exhibits strong unisensory visual deviance detection but weaker multisensory deviance detection. These results suggest that deviance detection signals in the cortex may be conceptualized as "prediction errors," which are primarily fed forward-or downstream-in cortical networks. 6 , 7 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: In 2017, the US Food and Drug Administration (FDA) approved a monthly injectable form of buprenorphine, extended-release buprenorphine; published data show that extended-release buprenorphine is effective compared with no treatment, but its current cost is higher and current retention is lower than that of transmucosal buprenorphine. Preliminary research suggests that extended-release buprenorphine may be an important addition to treatment options, but the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine remains unclear., Objective: To evaluate the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine., Design, Setting, and Participants: This economic evaluation used a state transition model starting in 2019 to simulate the lifetime of a closed cohort of individuals with OUD presenting for evaluation for opioid agonist treatment with buprenorphine. The data sources used to estimate model parameters included cohort studies, clinical trials, and administrative data. The model relied on pharmaceutical costs from the Federal Supply Schedule and health care utilization costs from published studies. Data were analyzed from September 2021 to January 2023., Interventions: No treatment, treatment with transmucosal buprenorphine, or treatment with extended-release buprenorphine., Main Outcomes and Measures: Mean lifetime costs per person, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs)., Results: The simulated cohort included 100 000 patients with OUD receiving (61% male; mean [SD] age, 38 [11] years) or not receiving medication treatment (58% male, mean [SD] age, 48 [18] years). Compared with no medication treatment, treatment with transmucosal buprenorphine yielded an ICER of $19 740 per QALY. Compared with treatment with transmucosal buprenorphine, treatment with extended-release buprenorphine yielded lower effectiveness by 0.03 QALYs per person at higher cost, suggesting that treatment with extended-release buprenorphine was dominated and not preferred. In probabilistic sensitivity analyses, treatment with transmucosal buprenorphine was the preferred strategy 60% of the time. Treatment with extended-release buprenorphine was cost-effective compared with treatment with transmucosal buprenorphine at a $100 000 per QALY willingness-to-pay threshold only after substantial changes in key parameters., Conclusions and Relevance: In this economic evaluation of extended-release buprenorphine compared with transmucosal buprenorphine for the treatment of OUD, extended-release buprenorphine was not associated with efficient allocation of limited resources when transmucosal buprenorphine was available. Future initiatives should aim to improve retention rates or decrease costs associated with extended-release buprenorphine.

Background: As more states pass recreational cannabis legalization (RCL), we must understand how RCL affects substance use. Objectives: The current study aims to examine the effect of RCL on lifetime and past-year use of cannabis, alcohol, tobacco, and other drugs, frequency of cannabis, alcohol, and tobacco use, co-use of cannabis with alcohol and tobacco, and consequences from cannabis and alcohol use. Methods: We used a unique, co-twin control design of twin pairs who were discordant for living in a state with RCL between 2018 and 2021. The sample consisted of 3,830 adult twins (41% male), including 232 twin pairs discordant for RCL. Problems from alcohol and cannabis use were assessed via the Brief Marijuana Consequences Questionnaire and the Brief Young Adult Alcohol Consequences Questionnaire. Results: Results indicated that the twin living in an RCL state was more likely to endorse past-year cannabis use (OR = 1.56, p  = .009), greater number of cannabis use days in the past 6 months (β = 0.47, p  = .019), but not more negative consequences from cannabis use (β = 0.21, p  = .456) compared to their co-twin in a non-RCL state. There were no differences within-twin pairs in frequency of alcohol use (β=-0.05, p  = .601), but the RCL twin reported fewer negative consequences from alcohol use (β=-0.29, p  = .016) compared to their co-twin in a non-RCL state. We did not observe any other differences within-twin pairs on other outcomes. Conclusion: These results suggest that living in an RCL state is associated with greater cannabis frequency but not more negative consequences from cannabis use than living in a non-RCL state.

Incidence of anxiety-like disorders in humans has been shown to decrease with aging; however, it is still under debate whether there are similarities in mice, which would support the use of mouse models in understanding the neuronal network changes that regulate anxiety-like behavior in aging. One of the most common tests used to assess anxiety-like behavior in laboratory animals is the elevated plus maze (EPM). Although several variables, such as room brightness and width of the maze arms, have been shown to influence the spontaneous animal behavior during the EPM test, none of these variables have ever been evaluated in aging to understand their possible differential effect on younger and older mice. We therefore decided to investigate the effect of apparatus construction on young adult and old mice of both sexes on EPM test performance. Our results show that distance traveled during the test is the variable that is most affected by apparatus characteristics independent of age and sex. We also found that apparatus construction was key in demonstrating that old mice spent more time and had relatively more entries in the open arms as compared to young mice, suggesting a decrease in anxiety-like behavior with age. Taken together, our data demonstrate that EPM apparatus characteristics dramatically affect test outcome with a wider arm apparatus being more effective in revealing age-dependent changes in anxiety-like behavior, thus, suggesting the use of a wider arm EPM when conducting aging studies in mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gaspar, Bartman, Coppotelli and Ross.)