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Executive attention, the attention necessary to reconcile conflict among simultaneous attentional demands, is vital to children's daily lives. This attention develops rapidly as the anterior cingulate cortex and prefrontal areas mature during early and middle childhood. However, the developmental course of executive attention is not uniform among children. Therefore, the purpose of this investigation was to examine the role of individual differences in the development of executive attention by exploring the concurrent and longitudinal contributions to its development at 8 years of age. Executive attention was predicted by concurrent measures of frontal electroencephalography, laboratory-based performance on a conflict task, and parent report of attention. Longitudinally, 8-year-old executive attention was significantly predicted by a combination of 4-year-old frontal activity, conflict task performance, and parent report of attention focusing, but not with an analogous equation replacing attention focusing with attention shifting. Together, data demonstrate individual differences in executive attention.

Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017–2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans.

As screening strategies employ better biomarkers and genetics to identify individuals at an increased risk of prostate cancer, there are currently no chemotherapeutic prevention strategies. With any chemoprevention strategy, the population will be younger and healthier; therefore, they will be less tolerant of side effects. This study translated findings from screening a natural product library and pre-clinical evaluation of curcumin (CURC) in combination with ursolic acid (UA) in prostate cancer models. After manufacturing capsules for each compound, 18 subjects were enrolled. The study used a 3 × 3 phase 1 clinical trial to evaluate CURC (1200 mg/day) and UA (300 mg/day) alone and in combination over a 2-week period with endpoints of safety, bioavailability, and microbiome alterations. After enrolling six subjects in each arm, we found no grade 3 or 4 events and only minor changes in the safety laboratory values. In the pooled analysis of groups, we noted a statistically significant difference between median serum levels of UA when administered alone vs administered in the combination (2.7 ng/mL vs 43.8 ng/mL, p = 0.03). Individuals receiving the combination also had a favorable impact on gut microbiome status and a reduction in “microbiome score” predictive of prostate cancer risk.

Abstract Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient’s age was 64 [42–76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3–10] days and the median total length of MV was 14 [10–23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials.

Abstract Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers.

Previous research has revealed that daily variations in human neurobehavioral functions are driven in part by the endogenous circadian system. The objective of this study was to explore whether there exists a circadian influence on performance regarding a risky decision-making task and to determine whether the performance changes with sleep deprivation (SD). Thirteen participants underwent a 39 h constant routine (CR) protocol, during which they remained awake in constant conditions and performed the BART (balloon analogue risk task) every two hours. The mean pumps (gains) (p < 0.001) and balloons popped (losses) (p = 0.003) exhibited variation during the CR. The reaction time (RT) also showed significant variation across the CR (p < 0.001), with slower mean RTs in the morning hours following SD. A greater risk propensity was observed around midday before SD and a lower risk propensity after 29.5 h of being awake. The sensitivity to punishment varied during the CR, but did not follow a predictable trend. Further research using real monetary incentives and neurophysiological measures is warranted to elucidate these findings.

Abstract Lattices remain an attractive class of structures due to their design versatility; however, rapidly designing lattice structures with tailored or optimal mechanical properties remains a significant challenge. With each added design variable, the design space quickly becomes intractable. To address this challenge, research efforts have sought to combine computational approaches with machine learning (ML)-based approaches to reduce the computational cost of the design process and accelerate mechanical design. While these efforts have made substantial progress, significant challenges remain in (1) building and interpreting the ML-based surrogate models and (2) iteratively and efficiently curating training datasets for optimization tasks. Here, we address the first challenge by combining ML-based surrogate modeling and Shapley additive explanation (SHAP) analysis to interpret the impact of each design variable. We find that our ML-based surrogate models achieve excellent prediction capabilities (R 2 > 0.95) and SHAP values aid in uncovering design variables influencing performance. We address the second challenge by utilizing active learning-based methods, such as Bayesian optimization, to explore the design space and report a 5 × reduction in simulations relative to grid-based search. Collectively, these results underscore the value of building intelligent design systems that leverage ML-based methods for uncovering key design variables and accelerating design.

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate the extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons. Exopher production from the C. elegans ALMR neuron peaks at adult day 2 or 3, coinciding with the C. elegans reproductive peak. Genetic disruption of C. elegans germline, sperm, oocytes, or egg/early embryo production can strongly suppress exopher extrusion from the ALMR neurons during the peak period. Conversely, restoring egg production at the late reproductive phase through mating with males or inducing egg retention via genetic interventions that block egg-laying can strongly increase ALMR exopher production. Overall, genetic interventions that promote ALMR exopher production are associated with expanded uterus lengths and genetic interventions that suppress ALMR exopher production are associated with shorter uterus lengths. In addition to the impact of fertilized eggs, ALMR exopher production can be enhanced by filling the uterus with oocytes, dead eggs, or even fluid, supporting that distention consequences, rather than the presence of fertilized eggs, constitute the exopher-inducing stimulus. We conclude that the mechanical force of uterine occupation potentiates exopher extrusion from proximal proteostressed maternal neurons. Our observations draw attention to the potential importance of mechanical signaling in extracellular vesicle production and in aggregate spreading mechanisms, making a case for enhanced attention to mechanobiology in neurodegenerative disease.

Across the animal kingdom, neural responses in the auditory cortex are suppressed during vocalization, and humans are no exception. A common hypothesis is that suppression increases sensitivity to auditory feedback, enabling the detection of vocalization errors. This hypothesis has been previously confirmed in non-human primates, however a direct link between auditory suppression and sensitivity in human speech monitoring remains elusive. To address this issue, we obtained intracranial electroencephalography (iEEG) recordings from 35 neurosurgical participants during speech production. We first characterized the detailed topography of auditory suppression, which varied across superior temporal gyrus (STG). Next, we performed a delayed auditory feedback (DAF) task to determine whether the suppressed sites were also sensitive to auditory feedback alterations. Indeed, overlapping sites showed enhanced responses to feedback, indicating sensitivity. Importantly, there was a strong correlation between the degree of auditory suppression and feedback sensitivity, suggesting suppression might be a key mechanism that underlies speech monitoring. Further, we found that when participants produced speech with simultaneous auditory feedback, posterior STG was selectively activated if participants were engaged in a DAF paradigm, suggesting that increased attentional load can modulate auditory feedback sensitivity.

Introduction Genetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings.Methods and analysis We will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives.Ethics and dissemination This study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals.Trial registration number NCT06455384.

Abstract T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation. We demonstrate that radiation results in loss of CD8 T cell recirculation from the tumor to the lymph node and to distant sites. Using scRNASeq, we see decreased proliferating CD8 T cells in the tumor following radiation therapy resulting in a proportional enrichment in exhausted phenotypes. By contrast, 5 days following radiation increased recirculation of T cells from the tumor to the tumor draining lymph node corresponds with increased immunosurveillance of the treated tumor. These data demonstrate that tumor radiation therapy transiently impairs systemic T cell recirculation from the treatment site to the draining lymph node and distant untreated tumors. This may inform timing therapies to improve systemic T cell-mediated tumor immunity.

Abstract Transcranial direct current stimulation (tDCS) exerts beneficial effects on motor recovery after stroke, presumably by enhancement of adaptive neural plasticity. However, patients with extensive damage may experience null or deleterious effects with the predominant application mode of anodal (excitatory) stimulation of the damaged hemisphere. In such cases, excitatory stimulation of the non-damaged hemisphere might be considered. Here we asked whether tDCS exerts a measurable effect on movement quality of the hemiparetic upper limb, following just a single treatment session. Such effect may inform on the hemisphere that should be excited. Using a single-blinded crossover experimental design, stroke patients and healthy control subjects were assessed before and after anodal, cathodal and sham tDCS, each provided during a single session of reaching training (repeated point-to-point hand movement on an electronic tablet). Group comparisons of endpoint kinematics at baseline—number of peaks in the speed profile (NoP; smoothness), hand-path deviations from the straight line (SLD; accuracy) and movement time (MT; speed)—disclosed greater NoP, larger SLD and longer MT in the stroke group. NoP and MT revealed an advantage for anodal compared to sham stimulation of the lesioned hemisphere. NoP and MT improvements under anodal stimulation of the non-lesioned hemisphere correlated positively with the severity of hemiparesis. Damage to specific cortical regions and white-matter tracts was associated with lower kinematic gains from tDCS. The study shows that simple descriptors of movement kinematics of the hemiparetic upper limb are sensitive enough to demonstrate gain from neuromodulation by tDCS, following just a single session of reaching training. Moreover, the results show that tDCS-related gain is affected by the severity of baseline motor impairment, and by lesion topography.

Abstract Although often located at a distance from their target gene promoters, enhancers are the primary genomic determinants of temporal and spatial transcriptional specificity in metazoans. Since the discovery of the first enhancer element in simian virus 40, there has been substantial interest in unraveling the mechanism(s) by which enhancers communicate with their partner promoters to ensure proper gene expression. These research efforts have benefited considerably from the application of increasingly sophisticated sequencing- and imaging-based approaches in conjunction with innovative (epi)genome-editing technologies; however, despite various proposed models, the principles of enhancer–promoter interaction have still not been fully elucidated. In this review, we provide an overview of recent progress in the eukaryotic gene transcription field pertaining to enhancer–promoter specificity. A better understanding of the mechanistic basis of lineage- and context-dependent enhancer–promoter engagement, along with the continued identification of functional enhancers, will provide key insights into the spatiotemporal control of gene expression that can reveal therapeutic opportunities for a range of enhancer-related diseases.

Abstract Schistosoma japonicum is endemic in the Philippines. The Kato-Katz (KK) method was used to diagnose S. japonicum. This is impractical, particularly when the sample size is limited. Knowledge on point-of-care circulating cathodic antigen (CCA) test performance for S. japonicum is limited. Determining the sensitivity and specificity of new diagnostics is difficult when the gold standard test is less effective or absent. Latent class analysis (LCA) can address some limitations. A total of 484 children and 572 adults from the Philippines were screened for S. japonicum. We performed Bayesian LCA to estimate the infection prevalence, sensitivity and specificity of each test by stratifying them into two age groups. Observed prevalence assessed by KK was 50.2% and 31.8%, and by CCA was 89.9% and 66.8%, respectively. Using Bayesian LCA, among children, the sensitivity and specificity of CCA were 94.8% (88.7–99.4) and 21.5% (10.5–36.1) while those of KK were 66.0% (54.2–83.3) and 78.1% (61.1–91.3). Among adults, the sensitivity and specificity of CCA were 86.4% (76.6–96.9) and 62.8% (49.1–81.1) while those of KK were 43.6% (35.1–53.9) and 85.5% (75.8–94.6). Overall, CCA was more sensitive than KK, regardless of the age group at diagnosis, as KK was more specific. KK and CCA have different diagnostic performance, which should inform their use in the planning and implementation of S. japonicum control programs.

Objective To report the relationship between visual impairment (VI) and cognitive impairment (CI) among the older population living in residential care homes in Hyderabad, India.Study design Cross-sectional study.Setting 41 homes for the aged centres in the Hyderabad region.Participants 965 participants aged ≥60 years from homes for the aged centres.Primary outcome measures Visual impairment and cognitive impairment.Methods The Hindi mini-Mental Status Examination (HMSE) questionnaire was used to assess the cognitive function. The final HMSE score was calculated after excluding vision-dependent tasks (HMSE-VI). A detailed eye examination was conducted, including visual acuity (VA) measurement for distance and near vision, using a standard logarithm of the minimum angle of resolution chart under good illumination. CI was defined as having a HMSE-VI score of ≤17. VI was defined as presenting VA worse than 6/12 in the better-seeing eye. Near VI (NVI) was defined as binocular presenting near vision worse than N8 and distance VA of 6/18 or better in the better-seeing eye. Multiple logistic regression was done to assess the association between VI and CI.Results The mean age (±SD) was 74.3 (±8.3) years (range: 60–97 years). There were 612 (63.4%) women, and 593 (61.5%) had a school education. In total, 260 (26.9%; 95% confidence intervals: 24.2 to 29.9) participants had CI. The prevalence of CI among those with VI was 40.5% compared with 14.6% among those without VI (p

Objective A grassroots environmental-justice organisation in Kansas City has been examining the disproportionate exposure to air pollution experienced by residents living fenceline to the largest classification railyard in the USA. Prior analyses showed limited increased risk for asthma exacerbation for patients with asthma living closer to toxic release inventory (TRI) facilities and railyards. In this study, we assessed geographical asthma and environmental disparities, to further explore community-level disparities.Design This is a cross-sectional study of population-level asthma rates, which included rates for all asthma encounters and acute asthma encounters (urgent care, emergency department, inpatient admission). Distances from census-tract centroids to nearest TRI facilities, railyards and highways were calculated. The association between asthma rates and distances was examined using Kendall’s τ correlation and multivariable Poisson regression models.Setting We used electronic medical record data from the regional paediatric hospital, census and Environmental Protection Agency (EPA) air monitoring data.Participants Patients with 2+ asthma encounters during the EPA study timeframe were identified.Results Residential distance from railyards exhibited a significant negative correlation with overall (−0.36 (CI −0.41 to –0.32)) and acute (−0.27 (CI −0.32 to –0.22)) asthma rates. Asthma rates were elevated among tracts north of the closest railyard (incident rate ratio: 1.38; CI 1.35 to 1.41) when compared with southern directionality. An increased distance from the nearest railyard of 3 km was associated with a decrease in overall asthma rates of 26%.Conclusion Significant negative associations between proximity to all pollution source types and asthma rates were observed. This community-level research has served as a tool for community engagement and will be used to support proposed local policy. Environmental justice work addresses local concerns involving small, limited datasets, if the data exist at all. The academic epidemiological platform may reconsider acceptable approaches to small population research in order to better serve communities with the most need.

Brain microvessels possess the unique properties of a blood–brain barrier (BBB), tightly regulating the passage of molecules from the blood to the brain neuropil and vice versa. In models of brain injury, BBB dysfunction and the associated leakage of serum albumin to the neuropil have been shown to induce pathological plasticity, neuronal hyper-excitability, and seizures. The effect of neuronal activity on BBB function and whether it plays a role in plasticity in the healthy brain remain unclear. Here we show that neuronal activity induces modulation of microvascular permeability in the healthy brain and that it has a role in local network reorganization. Combining simultaneous electrophysiological recording and vascular imaging with transcriptomic analysis in rats, and functional and BBB-mapping MRI in human subjects, we show that prolonged stimulation of the limb induces a focal increase in BBB permeability in the corresponding somatosensory cortex that is associated with long-term synaptic plasticity. We further show that the increased microvascular permeability depends on neuronal activity and involves caveolae-mediated transcytosis and transforming growth factor β signaling. Our results reveal a role of BBB modulation in cortical plasticity in the healthy brain, highlighting the importance of neurovascular interactions for sensory experience and learning.

Background In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation.Objective This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM).Trial design Single-centre, open-label, prospective RCT.Methods This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests.Ethics and dissemination Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT05850936.

Abstract Progressive Supranuclear Palsy (PSP) is an atypical parkinsonism. Major subtypes of the disease: PSP-Richardson’s Syndrome (PSP-RS) and PSP Parkinsonism Predominant (PSP-P) vary in clinical features, the pathomechanism remains unexplored. The aim of this work is to analyze the relevance of glial cell line-derived neurotrophic factor (GDNF) evaluation in the serum and cerebrospinal fluid (CSF) in PSP subtypes and to verify its significance as a possible factor in the in vivo examination. Authors assessed the concentration of GDNF in the serum and CSF of 12 patients with PSP-RS, 12 with PSP-P and 12 controls. Additionally authors evaluated patients using Unified Parkinson’s Disease Rating Scale—III part (UPDRS-III), Frontal Assessment Battery (FAB) and Magnetic Resonance Imaging (MRI). The evaluation revealed significantly increased concentrations of GDNF in the CSF among PSP-RS patients and substantially increased concentrations of GDNF in the serum in PSP-P. Though the GDNF concentrations differentiated PSP subtypes, no correlations between with clinical factors were observed however certain correlations with atrophic changes in MRI were detected. GDNF is a factor which may impact the pathogenesis of PSP. Possible implementation of GDNF as a therapeutic factor could be a perspective in the search for therapy in this currently incurable disease.

Abstract Background Anti-fat attitudes and weight-based discrimination are prevalent in healthcare settings and among healthcare practitioners and clinical trainees, and can result in immense harm to patients. There is increasing recognition that anti-fat bias in healthcare is a critical issue that must be addressed, but there is a dearth of evidence demonstrating sustained attitude and behavioural change among clinicians, illustrating a need for more innovative educational approaches and rigorous evaluation. We describe the co-design and delivery of a narrative-based continuing professional development curriculum aimed at raising awareness of weight-based bias and stigma. Methods Our research team of lived experience educators, clinicians and researchers collaboratively developed a series of seven podcast episodes comprised of narrative descriptions of lived experiences with and impacts of weight bias, stigma and discrimination in healthcare settings, as well as a post-podcast workshop to facilitate reflection and discussion between participants. The curriculum was piloted among 20 clinicians practicing at a large urban hospital in Mississauga, Canada. We explored feasibility, acceptability and learning impact by analyzing responses to questionnaires completed following each podcast episode and responses shared during the workshops and follow-up feedback sessions. Results We observed high acceptability and feasibility of the curriculum. Participants experienced the podcast as a practical and convenient learning format and the workshop as a valuable opportunity to collectively debrief and reflect. The learning impact of the curriculum was strong; participants described a range of emotions elicited by the podcasts, engaged in self-reflection, and expressed a desire to modify clinical approaches. Barriers to the application of learnings identified by participants include pervasiveness of the use of body mass index (BMI) as an indicator of risk and a criterion for referral; discomfort with difficult conversations; prevalent biomedical understandings about the association between weight and health; and clinicians’ defensiveness. Conclusion This pilot study yielded promising findings and demonstrated potential impact on weight bias and stigma among healthcare providers. Necessary next steps include conducting larger scale, rigorous evaluations of the curriculum among broader populations, both health professions trainees and current healthcare providers.

AbstractBackground The purposes of this study were to assess the current status of perceived social support and COVID-19 impact on quality of life, to investigate the association of perceived social support with the COVID-19 impact on quality of life, and to examine differences in perceived social support between better and worse COVID-19 impact on quality of life for the total sample and by gender.Methods Participants included 1296 university students (399 male, 871 female, 22 transgender, non-binary, or other) with a mean age of 21.5 (SD = 2.6 years) from a large public university in the Midwest region of the US. Students voluntarily completed two questionnaires and demographic information via Qualtrics based on a cross-sectional study design. The Multidimensional Scale of Perceived Social Support (MSPSS) is a 12-item survey used to assess an individual’s perception of social support from significant others, friends, and family. The COVID-19-Impact on Quality of Life scale (COVID-19 QoL) is a 6-item scale used to assess the impact of COVID-19 on quality of life. Data was analyzed using descriptive statistics, multiple linear regression, independent t-tests, and ANCOVA.Results Multiple linear regression showed that perceived social support from family was a significant predictor of COVID-19 QoL (F = 35.154, p

Black women continue to be disproportionally burdened by HIV. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention option, which is underused by Black women. While social network interventions (SNIs) have been widely researched and implemented among some groups vulnerable to HIV, little is known about social network characteristics among Black women. To learn more about the social networks of Black women vulnerable to HIV and their knowledge of and interest in PrEP, we conducted a cross-sectional survey among 109 Black women aged 18–45 years attending a family planning clinic in Chicago, Illinois. In our study, 44% of women reported that they were moderately to extremely concerned about HIV. Over half of participants (53%) had a small personal network size (i.e., less than two). No statistically significant associations between having larger network sizes and having previously heard of PrEP, having an interest in starting PrEP, or having good PrEP knowledge were detected. Open-ended responses revealed high levels of trust in network connections with matters related to sexual health. Additionally, nearly all (94%) of women reported that SNIs were a good idea to promote PrEP. Future network studies are needed to inform the development of effective intervention strategies for women.

Objective To report the prevalence and risk factors for the fear of falling (FOF) among older individuals living in residential care facilities in India.Design Cross-sectional study.Setting Homes for the aged centres in Hyderabad, India.Participants The study included individuals aged ≥60 years from homes for the aged centres. The participants underwent a comprehensive eye examination in make-shift clinics setup in homes. Trained investigators collected the personal and demographic information of the participants and administered the Patient Health Questionnaire-9 and Hearing Handicap Inventory for Elderly questionnaire in the vernacular language. FOF was assessed using the Short Falls Efficacy Scale. The presence of hearing and visual impairment in the same individual was considered dual sensory impairment (DSI). A multiple logistic regression analysis was done to assess the factors associated with FOF.Primary outcome measure FOF.Results In total, 867 participants were included from 41 homes for the aged centres in the analyses. The mean (±SD) age of the participants was 74.2 (±8.3) years (range 60–96 years). The prevalence of FOF was 56.1% (95% CI 52.7% to 59.4%; n=486). The multivariate analysis showed that those with DSI had eleven times higher odds of reporting FOF than those with no impairment (OR 11.14; 95% CI 3.15 to 41.4.) Similarly, those with moderate depression had seven times higher odds (OR 6.85; 95% CI 3.70 to 12.70), and those with severe depression had eight times higher odds (OR 8.13; 95% CI 3.50 to 18.90) of reporting FOF. A history of falls in the last year was also associated with increased odds for FOF (OR 1.52; 95% CI 1.03 to 2.26).Conclusion FOF is common among older individuals in residential care in India. Depression, falling in the previous year and DSI were strongly associated with FOF. A cross-disciplinary approach may be required to address FOF among the older people in residential care in India.

Introduction The increasing burden of non-communicable diseases, such as hypertension, diabetes and dyslipidaemia, presents key challenges to achieving optimal HIV care outcomes among ageing people living with HIV. These diseases are often comorbid and are exacerbated by psychosocial and structural inequities. This interaction among multiple health conditions and social factors is referred to as a syndemic. In the USA, there are substantial disparities by social position (ie, racial, ethnic and socioeconomic status) in the prevalence and/or control of non-communicable diseases and HIV. Intersecting stigmas, such as racism, classism and homophobia, may drive these health disparities by contributing to healthcare avoidance and by contributing to a psychosocial syndemic (stress, depression, violence victimisation and substance use), reducing success along the HIV and non-communicable disease continua of care. Our hypothesis is that marginalised populations experience disparities in non-communicable disease incidence, prevalence and control, mediated by intersectional stigma and the psychosocial syndemic.Methods and analysis Collecting data over a 4 year period, we will recruit sexual minority men (planned n=1800) enrolled in the MACS/WIHS Combined Cohort Study, a long-standing mixed-serostatus observational cohort in the USA, to investigate the following specific aims: (1) assess relationships between social position, intersectional stigma and the psychosocial syndemic among middle-aged and ageing sexual minority men, (2) assess relationships between social position and non-communicable disease incidence and prevalence and (3) assess relationships between social position and HIV and non-communicable disease continua of care outcomes, mediated by intersectional stigma and the psychosocial syndemic. Analyses will be conducted using generalised structural equation models using a cross-lagged panel model design.Ethics and dissemination This protocol is approved as a single-IRB study (Advarra Institutional Review Board: Protocol 00068335). We will disseminate results via peer-reviewed academic journals, scientific conferences, a dedicated website, site community advisory boards and forums hosted at participating sites.

Background: Amid rising rates of neonatal opioid withdrawal syndrome (NOWS) worldwide and in many regions of the USA, we conducted an audit study (“secret shopper study”) to evaluate the influence of county-level buprenorphine capacity and rurality on county-level NOWS rates. Methods: In 2019, up to three phone calls were made to buprenorphine prescribers in the state of Missouri (USA). County-level buprenorphine capacity was defined as the number of clinicians (across all specialties) accepting pregnant people divided by the number of births. Multivariable negative binomial regression models estimated associations between buprenorphine capacity, rurality, and county-level NOWS rates, controlling for potential confounders (i.e., poverty, unemployment, and physician shortages) that may correspond to higher rates of NOWS and lower rates of buprenorphine prescribing. Analyses were stratified using tertiles of county-level overdose rates (top, middle, and lowest 1/3 of overdose rates). Results: Of 115 Missouri counties, 81(70 %) had no buprenorphine capacity, 17(15 %) were low-capacity (

Abstract Electronic cigarettes (e-cigarettes) are a prevalent alternative to conventional nicotine cigarettes among smokers and people who have never smoked. Increased concentrations of serum free fatty acids (FFAs) are crucial in generating lipotoxicity. We studied the effects of acipimox, an antilipolytic drug, on e-cigarette-induced cardiac dysfunction. C57BL/6J wild-type mice on high fat diet were treated with saline, e-cigarette with 2.4% nicotine [e-cigarette (2.4%)], and e-cigarette (2.4%) plus acipimox for 12 weeks. Fractional shortening and ejection fraction were diminished in mice exposed to e-cigarettes (2.4%) compared with saline and acipimox-treated mice. Mice exposed to e-cigarette (2.4%) had increased circulating levels of inflammatory cytokines and FFAs, which were diminished by acipimox. Gene Set Enrichment Analysis revealed that e-cigarette (2.4%)-treated mice had gene expression changes in the G2/M DNA damage checkpoint pathway that was normalized by acipimox. Accordingly, we showed that acipimox suppressed the nuclear localization of phospho-p53 induced by e-cigarette (2.4%). Additionally, e-cigarette (2.4%) increased the apurinic/apyrimidinic sites, a marker of oxidative DNA damage which was normalized by acipimox. Mice exposed to e-cigarette (2.4%) had increased cardiac Heme oxygenase 1 protein levels and 4-hydroxynonenal (4-HNE). These markers of oxidative stress were decreased by acipimox. Therefore, inhibiting lipolysis with acipimox normalizes the physiological changes induced by e-cigarettes and the associated increase in inflammatory cytokines, oxidative stress, and DNA damage.

Abstract A new practical imaging technique was presented for metamaterial characterization and investigation by visualizations of the magnetic microwave near-field (H-MWNF) distributions on a metamaterial's surface using the method of thermo-elastic optical indicator microscopy (TEOIM). ITO-based transparent and ceramic-based opaque metamaterial structures were designed for magnetic near-field visualization. Depending on the incident microwave field polarization, the TEOIM system allows the characterization of the metamaterial properties and microwave interaction behavior. The working principle of the periodic structures was investigated through numerical simulations, and the obtained results exhibited strong agreement when compared with experimental observations. Moreover, the visualization of the H-MWNF revealed the potential to characterize and evaluate the absorption and transmission properties effectively.

Abstract The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those not exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 IgG II Quant assay) and neutralizing capacities (spike SARS-CoV-2 pseudovirus Wuhan and Omicron BA.1 variant) were measured after the third and fourth doses of a COVID-19 mRNA vaccine among 46 elderly residents (median age 85 years [IQR 81; 89]) of an assisted living facility. Among participants never infected by SARS-CoV-2, the mean serum IgG levels against RBD (2025 BAU/ml), 99 days after the fourth vaccine, was as high as 76 days after the third vaccine (1987 BAU/ml), and significantly higher (p = 0.030) when the latter were corrected for elapsed time. Neutralizing antibody levels against the historical Wuhan strain were significantly higher (Mean 1046 vs 1573; p = 0.002) and broader (against Omicron) (Mean 170 vs 375; p = 0.018), following the fourth vaccine. The six individuals with an Omicron breakthrough infection mounted strong immune responses for anti-RBD and neutralizing antibodies against the Omicron variant indicating that the fourth vaccine dose did not prevent a specific adaptation of the immune response. These findings point out the value of continued vaccine boosting in the elderly population

Introduction Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors.Method Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses.Analysis Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model.Ethics National Mutual Acceptance ethical approval was obtained from the Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC). Local approvals were planned to be sought in each jurisdiction, as per local ethics processes. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC.Dissemination Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.

Abstract Background: The Centers for Disease Control and Prevention (CDC)-funded Cancer Prevention and Control Research Network (CPCRN) has been a leader in cancer-related dissemination & implementation (D&I) science. Given increased demand for D&I research, the CPCRN Scholars Program launched in 2021 to expand the number of practitioners, researchers, and trainees proficient in cancer D&I science methods. Methods: The evaluation was informed by a logic model and data collected through electronic surveys. Through an application process (baseline survey), we assessed scholars’ competencies in D&I science domains/subdomains, collected demographic data, and asked scholars to share proposed project ideas. We distributed an exit survey one month after program completion to assess scholars’ experience and engagement with the program and changes in D&I competencies. A follow-up survey was administered to alumni nine months post-program to measure their continued network engagement, accomplishments, and skills. Results: Three cohorts completed the program, consisting of 20, 17, and 25 scholars in Years 1-3, respectively. There was a significant increase in the total D&I competency scores for all three cohorts for 4 overarching domains and 43 subdomains (MPre = 1.38 MPost = 1.89). Differences were greatest for the domain of Practice-Based Considerations (0.50 mean difference) and Theory & Analysis (0.47 mean difference). Alumni surveys revealed that scholars appreciated access to D&I-focused webinars, toolkits, and training resources. 80% remain engaged with CPCRN workgroups and investigators. Conclusions: Program evaluation with scholars and alumni helped with ongoing quality assurance, introspection, and iterative program adaptation to meet scholars’ needs. This approach is recommended for large-scale capacity-building training programs.

BackgroundLife course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging.ObjectivesThe Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health.PopulationParticipants in an ongoing prospective cohort study of weight-related health who identified as women.DesignRetrospective cohort study.MethodsIn 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80th percentile), moderate (20th-80th percentile), and low (Preliminary resultsNine hundred seventy-seven women (78%) completed the LEAP survey and 656 reported a live birth. Of these, 379 (58%) agreed to release medical records, and 250 records were abstracted (66% of the 379). Of the 977 survey respondents 769 (79%) reported attempting a pregnancy, and 656 (67%) reported at least one live birth. The validation subsample was similar to the overall cohort. Women with a high GWG had a higher adolescent BMI percentile and prevalence of unhealthy weight control behaviors than those with moderate or low GWG.ConclusionsLEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.

ObjectiveWe aimed to investigate sociodemographic factors associated with self-reported COVID-19 infection.MethodsThe study population was a prospective multicenter cohort of adult volunteers recruited from healthcare systems located in the mid-Atlantic and southern United States. Between April 2020 and October 2021, participants completed daily online questionnaires about symptoms, exposures, and risk behaviors related to COVID-19, including self-reports of positive SARS CoV-2 detection tests and COVID-19 vaccination. Analysis of time from study enrollment to self-reported COVID-19 infection used a time-varying mixed effects Cox-proportional hazards framework.ResultsOverall, 1,603 of 27,214 study participants (5.9%) reported a positive COVID-19 test during the study period. The adjusted hazard ratio demonstrated lower risk for women, those with a graduate level degree, and smokers. A higher risk was observed for healthcare workers, those aged 18-34, those in rural areas, those from households where a member attends school or interacts with the public, and those who visited a health provider in the last year.ConclusionsWe identified subgroups within healthcare network populations defined by age, occupational exposure, and rural location reporting higher than average rates of COVID-19 infection for our surveillance population. These subgroups should be monitored closely in future epidemics of respiratory viral diseases.

Osteoporosis is a disease characterized by loss of bone mass, where bones become fragile and more likely to fracture. Bone density begins to decrease at age 50, and a state of osteoporosis is defined by loss of more than 25%. Cellular senescence is a permanent arrest of normal cell cycle, while maintaining cell viability. The number of senescent cells increase with age. Since osteoporosis is an aging disease, it is natural to consider the question to what extend senescent cells induce bone density loss and osteoporosis. In this paper we use a mathematical model to address this question. We determine the percent of bone loss for men and women during age 50 to 100 years, and the results depend on the rate η of net formation of senescent cell, with η = 1 being the average rate. In the case η = 1, the model simulations are in agreement with empirical data. We also consider senolytic drugs, like fisetin and quercetin, that selectively eliminate senescent cells, and assess their efficacy in terms of reducing bone loss. For example, at η = 1, with estrogen hormonal therapy and early treatment with fisetin, bone density loss for women by age 75 is 23.4% (below osteoporosis), while with no treatment with fisetin it is 25.8% (osteoporosis); without even a treatment with estrogen hormonal therapy, bone loss of 25.3% occurs already at age 65.

BackgroundPost-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD symptoms.AimExamine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial.MethodsParticipants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms.ResultsAdjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting gender differences in this association were found in either the crude or adjusted models (all interaction p-valuesConclusionThese findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

[This corrects the article DOI: 10.1371/journal.pone.0239291.].

Alzheimer disease (AD) is the most common form of dementia. The cause of the disease is unknown, and it has no cure. Symptoms include cognitive decline, memory loss, and impairment of daily functioning. The pathological hallmarks of the disease are aggregation of plaques of amyloid-β (Aβ) and neurofibrillary tangles of tau proteins (τ), which can be detected in PET scans of the brain. The disease can remain asymptomatic for decades, while the densities of Aβ and τ continue to grow. Inflammation is considered an early event that drives the disease. In this paper, we develop a mathematical model that can produce simulated patterns of (Aβ,τ) seen in PET scans of AD patients. The model is based on the assumption that early inflammations, R and [Formula: see text], drive the growth of Aβ and τ, respectively. Recently approved drugs can slow the progression of AD in patients, provided treatment begins early, before significant damage to the brain has occurred. In line with current longitudinal studies, we used the model to demonstrate how to assess the efficacy of such drugs when given years before the disease becomes symptomatic.

BackgroundIrritable bowel syndrome (IBS) is a disorder of the gut-brain interaction that is associated with abdominal pain, altered bowel patterns, and reduced quality of life. Up to 50% of patients with IBS also report anxiety or depressive symptoms. Although effective self-management interventions exist for individuals with IBS, few have been effectively implemented, and most do not consider the unique needs of patients with comorbid IBS and anxiety or depression. ObjectiveThis study aimed to determine the anticipated acceptability, appropriateness, feasibility, and usability of a comprehensive self-management intervention using an implementation science and human-centered design approach among individuals with comorbid IBS and anxiety or depression and health care providers. MethodsA convergent mixed methods design was used to elicit feedback on the comprehensive self-management intervention outline and content to identify refinement needs before testing. Patients with IBS and moderate to severe anxiety or depression and health care providers were purposefully sampled from primary care and gastroenterology settings. Participants completed semistructured interviews and surveys on anticipated acceptability, appropriateness, feasibility, and usability. ResultsPatient participants (n=12) were on average 36.8 (SD 12.2) years of age, and 42% (5/12) were currently receiving psychological therapy. Health care providers (n=14) were from primary care (n=7) and gastroenterology (n=7) settings. The mean usability scores (out of 100) were 52.5 (SD 14.5) for patients and 45.6 (SD 11.6) for providers. For patients and providers, qualitative data expanded the quantitative findings for acceptability and appropriateness. Acceptability findings were the comprehensive nature of the intervention and discussion of the gut-brain interaction. For appropriateness, participants reported that the intervention provided structure, accountability, and support. Feasibility was confirmed for patients, but there was a divergence of findings between quantitative and qualitative measures for providers. Patients focused on intervention feasibility, while providers focused on implementation feasibility in the clinic. Identified usability issues to address before implementation included the intervention delivery format, length, and lack of integration into health care settings that, if not addressed, may limit the reach of the intervention. ConclusionsPatients and health care providers found the intervention acceptable and appropriate. Several feasibility and usability issues were identified, including intervention delivery methods, length of intervention, and the best methods to implement in the clinic setting. The next steps are to refine the intervention to address the identified issues and test in a pilot study whether addressing usability issues leads to the anticipated improvements in implementation and uptake.

Abstract Biofilm-state bacterial infections associated with inserted medical devices constitute a massive health and financial problem worldwide. Although bacteria exhibit significantly lower susceptibility to antibiotics in the biofilm state, the most common treatment approach still relies on antibiotics, exacerbating the phenomenon of antibiotic-resistant bacteria. In this study, we aimed to assess whether ZnCl2 coating of intranasal silicone splints (ISSs) can reduce the biofilm infections associated with the insertion of these devices and prevent the overuse of antibiotics while minimizing waste, pollution and costs. We tested the ability of ZnCl2 to prevent biofilm formation on ISS both in vitro and in vivo by using the microtiter dish biofilm formation assay, crystal violet staining, and electron and confocal microscopy. We found a significant decrease in biofilm formation between the treatment group and the growth control when ZnCl2-coated splints were placed in patients’ nasal flora. According to these results, infections associated with ISS insertion may be prevented by using ZnCl2 coating, thereby obviating the overuse and abuse of antibiotics.