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IntroductionSome caregivers are hesitant about topical fluoride for their children despite evidence that fluoride prevents caries and is safe. Recent work described a five domain model of caregivers' topical fluoride hesitancy. We developed the Fluoride Hesitancy Identification Tool (FHIT) item pool based on the model. This study sought to evaluate the FHIT's psychometric properties in an effort to generate a short, simple to score, reliable, and valid tool that measures caregivers' topical fluoride hesitancy.MethodsIn 2021 and 2022, we conducted an observational, cross-sectional study of caregivers, collecting data from two independent caregiver samples (n1 = 523; n2 = 612). The FHIT item pool included 33 items. We used confirmatory factor analyses (CFA) to examine whether the FHIT items measured five separate domains as hypothesized and to reduce the number of items. We then fit item response theory (IRT) models and computed Cronbach's alpha for each domain. Last, we examined the construct validity of the FHIT and evaluated scoring approaches.ResultsAfter dropping 8 items, CFA supported a five factor model of topical fluoride hesitancy, with no cross-loadings (RMSEA = 0.079; SRMR = 0.057; CFI = 0.98; TLI = 0.98). We further reduced the items to four per domain (20 items total). Marginal alphas showed that the item sets provided reliability of ≥0.90 at hesitancy levels at and above average. The domains correlated more strongly with each other and topical fluoride refusal than with other questions on the survey.DiscussionOur results support the FHIT's ability to reliably and validly measure five domains of topical fluoride hesitancy using the average score of the four items in each domain.

Adaptive gain theory proposes that the dynamic shifts between exploration and exploitation control states are modulated by the locus coeruleus-norepinephrine system and reflected in tonic and phasic pupil diameter. This study tested predictions of this theory in the context of a societally important visual search task: the review and interpretation of digital whole slide images of breast biopsies by physicians (pathologists). As these medical images are searched, pathologists encounter difficult visual features and intermittently zoom in to examine features of interest. We propose that tonic and phasic pupil diameter changes during image review may correspond to perceived difficulty and dynamic shifts between exploration and exploitation control states. To examine this possibility, we monitored visual search behavior and tonic and phasic pupil diameter while pathologists (N = 89) interpreted 14 digital images of breast biopsy tissue (1,246 total images reviewed). After viewing the images, pathologists provided a diagnosis and rated the level of difficulty of the image. Analyses of tonic pupil diameter examined whether pupil dilation was associated with pathologists difficulty ratings, diagnostic accuracy, and experience level. To examine phasic pupil diameter, we parsed continuous visual search data into discrete zoom-in and zoom-out events, including shifts from low to high magnification (e.g., 1× to 10×) and the reverse. Analyses examined whether zoom-in and zoom-out events were associated with phasic pupil diameter change. Results demonstrated that tonic pupil diameter was associated with image difficulty ratings and zoom level, and phasic pupil diameter showed constriction upon zoom-in events, and dilation immediately preceding a zoom-out event. Results are interpreted in the context of adaptive gain theory, information gain theory, and the monitoring and assessment of physicians diagnostic interpretive processes.

BackgroundTopical fluoride hesitancy is a well-documented and growing public health problem. Despite extensive evidence that topical fluoride is safe and prevents tooth decay, an increasing number of caregivers are hesitant about their children receiving topical fluoride, leading to challenges in clinical settings where caregivers refuse preventive care.PurposeTo explore the determinants of topical fluoride hesitancy for caregivers with dependent children.MethodsIn this qualitative study, we interviewed 56 fluoride-hesitant caregivers to develop an inductive conceptual model of reasons why caregivers are hesitant.ResultsThe core construct of the conceptual model of topical fluoride hesitancy centered on caregivers "wanting to protect and not mess up their child". Six domains comprised this core construct: thinking topical fluoride is unnecessary, wanting to keep chemicals out of my child's body, thinking fluoride is harmful, thinking there is too much uncertainty about fluoride, feeling pressured to get topical fluoride, and feeling fluoride should be a choice.ConclusionsTopical fluoride hesitancy is complex and multifactorial. Study findings provide insight for future efforts to understand and optimize caregivers' preventive care decision making.

Beyond sex as a binary or biological variable, within-sex variations related to sociocultural gender variables are of increasing interest in psychiatric research to better understand individual differences. Using a data-driven approach, we developed a composite gender score based on sociodemographic and psychosocial variables showing sex differences in a sample of psychiatric emergency patients upon admission (N = 1708; 39.4% birth-assigned females; mean age = 40 years; age standard deviation = 14). This gender score was extracted from a confirmatory factor analysis (CFI = 0.966; RMSEA = 0.044, SRMR = 0.030) and could predict a person's birth-assigned sex with 67% accuracy. This score allowed the further identification of differences on impulsivity measures that were absent when looking solely at birth-assigned sex. Female birth-assigned sex was also associated with higher rates of mood and personality disorder diagnoses, while higher feminine gender scores were related to higher proportions of anxiety and mood disorder diagnoses. By contrast, male birth-assigned sex and higher masculine gender scores were associated with higher proportions of psychotic and substance use disorder diagnoses. Patients with undifferentiated gender scores (i.e., scoring between masculine and feminine threshold defined by terciles) were more represented in the psychotic disorder group. Considering both sex and gender in psychiatric research is essential and can be achieved even when using secondary data to index gender comprised of demographic and psychosocial variables.

IntroductionUnderstanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia.MethodsWe performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures.ResultsData from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, pConclusionIn men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Obesity, along with its associated health issues, is closely tied to lifestyle habits. While certain elements affecting childhood health, such as genetics and ethnicity, are beyond individuals' control, there exists modifiable lifestyle behaviours that can facilitate healthier living. This study employed multiple regression analysis to investigate the relationship between specific modifiable lifestyle behaviours and self-reported health. The independent variables considered included days of moderate to vigorous physical activity (MVPA), fruit and vegetable consumption, breakfast frequency, school night sleep duration, and non-school night sleep duration. These variables were chosen for their practical modifiability within participants' daily lives. The analysis revealed a highly significant overall model (F(13,11363) = 191.117, p < .001), explaining 17.9% of the variance in self-reported health. Notably, higher MVPA levels were associated with improved self-reported health (B = 0.136 to 0.730, p < .001). Additionally, regular breakfast consumption and increased fruit and vegetable intake exhibited positive associations with self-reported health (B = 0.113 to 0.377, p < .001), while girls reported lower self-reported health (B = -0.079, p < .001). School night sleep duration was positively linked to self-reported health (B = 0.071, p < .001). Furthermore, a dose-response relationship between MVPA, dietary habits, and health was identified. These findings hold substantial potential for public health campaigns to promote healthy behaviours and prevent chronic diseases in young individuals. It is imperative to emphasise that all the variables considered in this study are readily modifiable aspects of individuals' lives, offering a promising avenue for personal health and well-being enhancement.

Updated recommendations on preseason heat safety in high school (HS) athletics ("2021 Consensus Statements") were published in April 2021. This cross-sectional survey study explored the initial roll-out of the 2021 Consensus Statements, including their visibility among United States HS athletic trainers (ATs) and perceived levels of confidence in implementing them. Recruitment occurred first, from a random selection of ATs from the Board of Certification, Inc., and second, an open invitation via social media. An online cross-sectional questionnaire had participating ATs note whether they had seen the 2021 Consensus Statements. If yes, ATs reported their perceived level of confidence in implementing them (5-point-ordinal scale from "not at all confident" to "very confident); if no, ATs disclosed (open-ended) why they had not yet seen them. Descriptive statistics were calculated for quantitative variables; template analysis identified codes related to visibility of and confidence in implementing 2021 Consensus Statements. Nearly half (45.7%) of 116 responding HS ATs reported having seen at least one 2021 Consensus Statements; 23.3% had reviewed all three. Common reasons among the 63 that had not seen them included: not aware they were published (n = 22), have yet to read them (n = 19), and believed they could not access the journal (n = 10). Of the 53 ATs having seen at least one of the 2021 Consensus Statements, 67.9% (n = 36) were very/fairly confident in implementing them at their HS. Reasons for confidence included their schools ensuring up-to-date EHI prevention and management practices (n = 18) and athletics constituent support (n = 8). This exploratory study observed proportions of surveyed HS ATs that had not seen the 2021 Consensus Statements and were not confident in implementing them. Findings highlight the need to continue improving messaging about access to best-practice recommendations. Further, continued efforts inclusive of active and passive dissemination strategies across all athletics constituents are needed to aid proper implementation.

BackgroundThe COVID-19 pandemic led to the implementation of a national policy of shielding to safeguard clinically vulnerable patients. To ensure consistent care for high-risk patients with hypertension, NHS England introduced the BP@home initiative to enable patients to self-monitor their blood pressure by providing them with blood pressure monitors. This study aimed to identify barriers and facilitators to the implementation of the initiative based on the experience and perspectives of programme managers and healthcare professionals (HCPs) involved in its implementation in London.Methods and findingsWe conducted five semi-structured focus groups and one individual interview with a total of 20 healthcare professionals involved at different levels and stages in the BP@home initiative across four of the five London Integrated Care Systems (ICSs). All focus groups and interviews were audio-recorded, transcribed and analysed thematically following the Framework Method. Respondents reported being challenged by the lack of adequate IT, human and financial resources to support the substantial additional workload associated with the programme. These issues resulted in and reinforced the differential engagement capacities of PCNs, practices and patients, thus raising equity concerns among respondents. However respondents also identified several facilitators, including the integration of the eligibility criteria into the electronic health record (EHR), especially when combined with the adoption of practice-specific, pragmatic and opportunistic approaches to the onboarding of patients. Respondents also recommended the provision of blood pressure monitors (BPMs) on prescription, additional funding and training based on needs assessment, the incorporation of BP@home into daily practice and simplification of IT tools, and finally the adoption of a person-centred care approach. Contextualised using the second iteration of the Consolidated Framework for Implementation Research (CFIR), these findings support key evidence-based recommendations to help streamline the implementation of the BP@home initiative in London's primary care setting.ConclusionsPrograms such as BP@Home are likely to become more common in primary care. To successfully support HCPs' aim to care for their hypertensive patients, their implementation must be accompanied by additional financial, human and training resources, as well as supported task-shifting for capacity building. Future studies should explore the perspectives of HCPs based in other parts of the UK as well as patients' experiences with remote monitoring of blood pressure.

IntroductionSome caregivers are hesitant about topical fluoride for their children despite evidence that fluoride prevents caries and is safe. Recent work described a five domain model of caregivers' topical fluoride hesitancy. We developed the Fluoride Hesitancy Identification Tool (FHIT) item pool based on the model. This study sought to evaluate the FHIT's psychometric properties in an effort to generate a short, simple to score, reliable, and valid tool that measures caregivers' topical fluoride hesitancy.MethodsIn 2021 and 2022, we conducted an observational, cross-sectional study of caregivers, collecting data from two independent caregiver samples (n1 = 523; n2 = 612). The FHIT item pool included 33 items. We used confirmatory factor analyses (CFA) to examine whether the FHIT items measured five separate domains as hypothesized and to reduce the number of items. We then fit item response theory (IRT) models and computed Cronbach's alpha for each domain. Last, we examined the construct validity of the FHIT and evaluated scoring approaches.ResultsAfter dropping 8 items, CFA supported a five factor model of topical fluoride hesitancy, with no cross-loadings (RMSEA = 0.079; SRMR = 0.057; CFI = 0.98; TLI = 0.98). We further reduced the items to four per domain (20 items total). Marginal alphas showed that the item sets provided reliability of ≥0.90 at hesitancy levels at and above average. The domains correlated more strongly with each other and topical fluoride refusal than with other questions on the survey.DiscussionOur results support the FHIT's ability to reliably and validly measure five domains of topical fluoride hesitancy using the average score of the four items in each domain.

BackgroundThe electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored.MethodsWe performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted meta-analysis.ResultsWe identified six loci associated with QRS (P

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are potentially life-threatening conditions whose partially overlapping phenomenology-distorted perception of appearance, obsessions/compulsions, and limited insight-can make diagnostic distinction difficult in some cases. Accurate diagnosis is crucial, as the effective treatments for AN and BDD differ. To improve diagnostic accuracy and clarify the contributions of each of the multiple underlying factors, we developed a two-stage machine learning model that uses multimodal, neurobiology-based, and symptom-based quantitative data as features: task-based functional magnetic resonance imaging data using body visual stimuli, graph theory metrics of white matter connectivity from diffusor tensor imaging, and anxiety, depression, and insight psychometric scores. In a sample of unmedicated adults with BDD (n = 29), unmedicated adults with weight-restored AN (n = 24), and healthy controls (n = 31), the resulting model labeled individuals with an accuracy of 76%, significantly better than the chance accuracy of 35% ([Formula: see text]). In the multivariate model, reduced white matter global efficiency and better insight were associated more with AN than with BDD. These results improve our understanding of the relative contributions of the neurobiological characteristics and symptoms of these disorders. Moreover, this approach has the potential to aid clinicians in diagnosis, thereby leading to more tailored therapy.

ObjectivesIndependently, physical activity (PA), sedentary behavior (SB), and sleep are related to the development and progression of chronic diseases. Less is known about how rest-activity behaviors cluster within individuals and how rest-activity behavior profiles relate to health. In this study we aimed to investigate if adult women cluster into profiles based on how they accumulate rest-activity behavior (including accelerometer-measured PA, SB, and sleep), and if participant characteristics and health outcomes differ by profile membership.MethodsA convenience sample of 372 women (mean age 55.38 + 10.16) were recruited from four US cities. Participants wore ActiGraph GT3X+ accelerometers on the hip and wrist for a week. Total daily minutes in moderate-to-vigorous PA (MVPA) and percentage of wear-time spent in SB was estimated from the hip device. Total sleep time (hours/minutes) and sleep efficiency (% of in bed time asleep) were estimated from the wrist device. Latent profile analysis (LPA) was performed to identify clusters of participants based on accumulation of the four rest-activity variables. Adjusted ANOVAs were conducted to explore differences in demographic characteristics and health outcomes across profiles.ResultsRest-activity variables clustered to form five behavior profiles: Moderately Active Poor Sleepers (7%), Highly Actives (9%), Inactives (41%), Moderately Actives (28%), and Actives (15%). The Moderately Active Poor Sleepers (profile 1) had the lowest proportion of whites (35% vs 78-91%, p < .001) and college graduates (28% vs 68-90%, p = .004). Health outcomes did not vary significantly across all rest-activity profiles.ConclusionsIn this sample, women clustered within daily rest-activity behavior profiles. Identifying 24-hour behavior profiles can inform intervention population targets and innovative behavioral goals of multiple health behavior interventions.

BackgroundAgeing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia.MethodsWe compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial.ResultsNeither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone.ConclusionThese data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

BackgroundAngiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study.MethodsSarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables.ResultsAllele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo.ConclusionOur results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Adaptive gain theory proposes that the dynamic shifts between exploration and exploitation control states are modulated by the locus coeruleus-norepinephrine system and reflected in tonic and phasic pupil diameter. This study tested predictions of this theory in the context of a societally important visual search task: the review and interpretation of digital whole slide images of breast biopsies by physicians (pathologists). As these medical images are searched, pathologists encounter difficult visual features and intermittently zoom in to examine features of interest. We propose that tonic and phasic pupil diameter changes during image review may correspond to perceived difficulty and dynamic shifts between exploration and exploitation control states. To examine this possibility, we monitored visual search behavior and tonic and phasic pupil diameter while pathologists (N = 89) interpreted 14 digital images of breast biopsy tissue (1,246 total images reviewed). After viewing the images, pathologists provided a diagnosis and rated the level of difficulty of the image. Analyses of tonic pupil diameter examined whether pupil dilation was associated with pathologists’ difficulty ratings, diagnostic accuracy, and experience level. To examine phasic pupil diameter, we parsed continuous visual search data into discrete zoom-in and zoom-out events, including shifts from low to high magnification (e.g., 1× to 10×) and the reverse. Analyses examined whether zoom-in and zoom-out events were associated with phasic pupil diameter change. Results demonstrated that tonic pupil diameter was associated with image difficulty ratings and zoom level, and phasic pupil diameter showed constriction upon zoom-in events, and dilation immediately preceding a zoom-out event. Results are interpreted in the context of adaptive gain theory, information gain theory, and the monitoring and assessment of physicians’ diagnostic interpretive processes.

Background Topical fluoride hesitancy is a well-documented and growing public health problem. Despite extensive evidence that topical fluoride is safe and prevents tooth decay, an increasing number of caregivers are hesitant about their children receiving topical fluoride, leading to challenges in clinical settings where caregivers refuse preventive care. Purpose To explore the determinants of topical fluoride hesitancy for caregivers with dependent children. Methods In this qualitative study, we interviewed 56 fluoride-hesitant caregivers to develop an inductive conceptual model of reasons why caregivers are hesitant. Results The core construct of the conceptual model of topical fluoride hesitancy centered on caregivers “wanting to protect and not mess up their child”. Six domains comprised this core construct: thinking topical fluoride is unnecessary, wanting to keep chemicals out of my child’s body, thinking fluoride is harmful, thinking there is too much uncertainty about fluoride, feeling pressured to get topical fluoride, and feeling fluoride should be a choice. Conclusions Topical fluoride hesitancy is complex and multifactorial. Study findings provide insight for future efforts to understand and optimize caregivers’ preventive care decision making.

Middle school (MS) is an intermediary level of education between elementary and secondary school that typically includes students aged 10-15 years. There is limited research within the MS sport setting, particularly related to sport-related injury prevention. This qualitative study aimed to better understand the sport culture within MS sports and the communication strategies used among invested groups (i.e., athletes, parents, staff inclusive of coaches and school nurses). Semi-structured interviews were conducted with 19 athletes, 20 parents, and 18 staff (e.g., coaches, school nurses) from seven MS in two school districts during the 2018/19 and 2019/20 school years. Topics focused on understanding school- and sport-related factors related to education, safety, and communication. Analysis used a consensual qualitative research tradition, in which the research team discussed individually developed themes and categories from transcribed interviews, with the goal of coming to a consensus and creating a codebook. Throughout the coding process, the research team would reconvene to discuss coding decisions until consensus was reached. This study focuses on the themes of sport culture and communication. Dominant categories identified within sport culture related to participants noting why they were interested in MS sports, and their struggles with their perceived roles and engagement (e.g., helping parents stay engaged, finding coaches, oversight of school nurses). Competitiveness and safety could have conflicting roles and priority. Dominant categories identified within communication centered around limited communication between coaches and parents. Technological assistance (e.g., phone apps, websites) was available, but often varied by school and sport. Concussions were seldom discussed unless during the preseason meeting or when one occurred. Findings highlight that the MS sport settings may struggle with incorporating primary prevention into their cultures and ensuring reliable communication among individuals. Novel and tailored approaches to injury prevention are needed to help ensure buy-in and proper implementation.

Background Relationships between the constructs of concussion-related knowledge, attitudes, and norms and their influence on observed care-seeking behaviors have previously been examined. Current models posit that these constructs serve as potential mediators of care-seeking behaviors; however, the dynamics between them have yet to be reconciled. Methods A cross-sectional, online survey explored relationships among the latent constructs of concussion-related knowledge, attitudes, and norms in parents of middle school children who participate in sports in multiple settings. A just-identified and two overidentified path models were explored and compared in an effort to understand such relationships. Results A total of 426 parents of United States middle school students were surveyed and included in analyses (mean age = 38.7±9.9 years; 55.6% female; 51.4% white/non-Hispanic; 56.1% with at least a bachelor’s degree). All parents had middle school aged children who participated in sport in both the club and school settings. The best fitting model was a just-identified model with concussion-related norms influencing concussion-related knowledge and attitudes, and concussion-related knowledge influencing attitudes. This model accounted for 14% of the variance in attitude and 12% of the variance in knowledge. Conclusions Study findings suggest that the constructs of concussion-related knowledge, attitudes and norms are directly related to one another, yet the dynamics of such relationships may be complex. As such, a parsimonious interpretation of these constructs may not be appropriate. Future research should work to further reconcile the dynamics between these constructs, and the impact these dynamics may have in influencing care-seeking behaviors beyond serving as mediators.

BackgroundGait impairments in Parkinson's disease (PD) limit independence and quality of life. While dance-based interventions could improve gait, further studies are needed to determine if the benefits generalise to different terrains and when dual-tasking. The aim was to assess the effects of a dance intervention, based on the Dance for PD® (DfPD®) program, on gait under different dual-tasks (verbal fluency, serial subtraction) and surfaces (even, uneven), and to determine if a larger scale follow-up RCT is warranted.MethodsA dance group (DG; n = 17; age = 65.8 ± 11.7 years) and a control group (CG: n = 16; age = 67.0 ± 7.7 years) comprised of non-cognitively impaired (Addenbrooke's score: DG = 93.2 ± 3.6, CG = 92.6 ± 4.3) independently locomoting people with PD (Hoehn & Yahr I-III). The DG undertook a one-hour DfPD®-based class, twice weekly for 12 weeks. The CG had treatment as usual. The spatiotemporal variables of gait were assessed at baseline and post-intervention while walking on two surfaces (even, uneven) under three conditions: regular walking; dual-task: verbal-fluency (DTVERB), and serial-subtraction (DTSUBT). The data were analysed by means of a linear mixed model.ResultsAt baseline, there was no significant group difference for any spatiotemporal gait variable. The DG improved significantly compared to the CG with and without a dual task when walking on even surface. During regular walking, DG improved in gait velocity (p = 0.017), cadence (p = 0.039), step length (p = 0.040) and stride length (p = 0.041). During DTVERB significant improvements were noted in gait velocity (p = 0.035), cadence (p = 0.034) and step length (p = 0.039). The DG also exhibited significant improvement compared to the CG during DTSUBT in the measures of gait velocity (p = 0.012), cadence (p = 0.021), step length (p = 0.018), and stride length (p = 0.151). On the uneven surface, improvements were noted when walking while performing serial subtractions only. During regular walking, improvements were noted for the CG but not for the DG. CG has spent less time in double support following the intervention than DG. While DTVERB condition had no significant group differences for any gait parameter (p's >0.05), in the DTSUBT condition, the DG improved significantly compared to the controls on gait velocity (p = 0.048), cadence (p = 0.026), and step length (p = 0.051).ConclusionsDfPD®-based classes produced clinically significant improvement in spatiotemporal gait parameters under dual-task conditions and on uneven surfaces. This could arise from improved movement confidence and coordination; emotional expression; cognitive skills (planning, multitasking), and; utilisation of external movement cues. A large-scale RCT of this program is warranted.Trial registrationA protocol for this study has been registered retrospectively at the Australian New Zealand Clinical Trials Registry. Identifier: ACTRN12618001834246.

Obesity and its impact on health is a multifaceted phenomenon encompassing many factors, including demographics, environment, lifestyle, and psychosocial functioning. A systems science approach, investigating these many influences, is needed to capture the complexity and multidimensionality of obesity prevention to improve health. Leveraging baseline data from a unique clinical cohort comprising 333 postmenopausal overweight or obese breast cancer survivors participating in a weight-loss trial, we applied Bayesian networks, a machine learning approach, to infer interrelationships between lifestyle factors (e.g., sleep, physical activity), body mass index (BMI), and health outcomes (biomarkers and self-reported quality of life metrics). We used bootstrap resampling to assess network stability and accuracy, and Bayesian information criteria (BIC) to compare networks. Our results identified important behavioral subnetworks. BMI was the primary pathway linking behavioral factors to glucose regulation and inflammatory markers; the BMI-biomarker link was reproduced in 100% of resampled networks. Sleep quality was a hub impacting mental quality of life and physical health with > 95% resampling reproducibility. Omission of the BMI or sleep links significantly degraded the fit of the networks. Our findings suggest potential mechanistic pathways and useful intervention targets for future trials. Using our models, we can make quantitative predictions about health impacts that would result from targeted, weight loss and/or sleep improvement interventions. Importantly, this work highlights the utility of Bayesian networks in health behaviors research.

Background: Prolonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most) is unclear.Methods: In preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a) 2 minutes standing every 20 minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD). Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models) were used to test statistical significance within the small sample size.Results: Nine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal compared to the first meal (i.e., condition-matched 2-hour post-lunch glucose iAUC was lower than 2-hour post-breakfast glucose iAUC) that withstood Bonferroni correction (p = 0.0024 and p = 0.0084, respectively). Using allometrically scaled data, the 10-minute standing every hour condition resulted in an improved FMD response, which was significantly greater than the control condition after Bonferroni correction (p = 0.0033).Conclusion: This study suggests that brief interruptions in prolonged sitting time have modality-specific glucoregulatory and vascular benefits and are feasible in an older adult population. Larger laboratory and real-world intervention studies of pragmatic and effective methods to change sitting habits are needed.ClinicalTrials.gov NCT02743286.

Physical activity and time spent outdoors may be important non-pharmacological approaches to improve sleep quality and duration (or sleep patterns) but there is little empirical research evaluating the two simultaneously. The current study assesses the role of physical activity and time outdoors in predicting sleep health by using objective measurement of the three variables. A convenience sample of 360 adult women (mean age = 55.38 ±9.89 years; mean body mass index = 27.74 ±6.12) was recruited from different regions of the U.S. Participants wore a Global Positioning System device and ActiGraph GT3X+ accelerometers on the hip for 7 days and on the wrist for 7 days and 7 nights to assess total time and time of day spent outdoors, total minutes in moderate-to-vigorous physical activity per day, and 4 measures of sleep health, respectively. A generalized mixed-effects model was used to assess temporal associations between moderate-to-vigorous physical activity, outdoor time, and sleep at the daily level (days = 1931) within individuals. There was a significant interaction (p = 0.04) between moderate-to-vigorous physical activity and time spent outdoors in predicting total sleep time but not for predicting sleep efficiency. Increasing time outdoors in the afternoon (versus morning) predicted lower sleep efficiency, but had no effect on total sleep time. Time spent outdoors and the time of day spent outdoors may be important moderators in assessing the relation between physical activity and sleep. More research is needed in larger populations using experimental designs.

Brooding rumination is positively associated with symptoms of both depression and posttraumatic stress disorder (PTSD). However, non-clinical cross-cultural research indicates that culture may influence these associations. This study aimed to examine the moderating effect of cultural group (Australian versus Malaysian) on the associations between brooding rumination and symptoms of depression and PTSD. European Australians (n = 109) and Malaysians of varying Asian heritages (n = 144) completed an online questionnaire containing the Hospital Anxiety and Depression Scale, PTSD checklist for DSM-5 and the Ruminative Response Scale-Short Form. First, Malaysian participants had higher brooding rumination than Australian participants. Second, higher levels of brooding rumination were positively associated with depression and PTSD symptom severity. Third, contrary to our expectations, cultural group did not moderate the relationships between brooding rumination and symptoms of depression and PTSD. If replicable, these results suggest that existing assessment and treatment approaches that target brooding rumination may apply to Malaysian individuals with depression and PTSD.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15-21) years in men and 18 (IQR 15-21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5-8.9) years in men and 8.2 (IQR 6.1-10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983.

The objective of this study was to examine associations of lifetime concussion history (CHx) and an advanced metric of lifetime repetitive head impact exposure with resting-state functional connectivity (rsFC) across the whole-brain and among large-scale functional networks (Default Mode; Dorsal Attention; and Frontoparietal Control) in former collegiate football players. Individuals who completed at least one year of varsity collegiate football were eligible to participate in this observational cohort study (n = 48; aged 36-41 years; 79.2% white/Caucasian; 12.5±4.4 years of football played; all men). Individuals were excluded if they reported history/suspicion of psychotic disorder with active symptoms, contraindications to participation in study procedures (e.g., MRI safety concern), or inability to travel. Each participant provided concussion and football playing histories. Self-reported concussion history was analyzed in two different ways based on prior research: dichotomous "High" (≥3 concussions; n = 28) versus "Low" (

IntroductionThe teaching and learning experience of allied health and healthcare science students has altered because of the Covid-19 pandemic. Limited research has explored the experience on the future healthcare workforce using participatory research design. The aim of this study was to explore the impact of a global pandemic on the clinical and academic experiences of healthcare student using a co-production approach with student peer researchers.MethodsA participatory research approach adopting online focus groups facilitated by students trained as peer researchers was adopted. First, second and final year students from occupational therapy, physiotherapy, podiatry, healthcare science, diagnostic radiography and imaging, radiotherapy and oncology, and speech and language therapy were recruited to six focus groups. Data generated through focus groups were analysed thematically using the DEPICT model to support a partnership approach.ResultsTwenty-three participants took part in six focus groups. The themes identified were: rapid changes to learning; living alongside Covid-19 and psychological impact. Students preferred blended learning approaches when available, as reduced peer interaction, studying and sleeping in the same space, and technology fatigue decreased motivation.ConclusionDue to rapid changes in learning and the stress, anxiety and isolation created by the pandemic, managing study, personal life and placement resulted in a gap in confidence in clinical skills development for students. Students took their professional identity seriously, engaged in behaviours to reduce transmission of Covid-19 and employed a range of coping strategies to protect wellbeing. A challenge with the move to online delivery was the absence of informal peer learning and students indicated that moving forward they would value a hybrid approach to delivery. Higher Education should capitalise on innovative learning experiences developed during the pandemic however it is important to research the impact this has on student skill acquisition and learning experience.

Background Coronavirus disease 2019 has impacted upon the role and safety of healthcare workers, with the potential to have a lasting effect on their wellbeing. Limited research has been conducted during previous pandemics exploring how student healthcare workers are impacted as they study and train for their professional careers. Objective The aim of the current study was to examine the specific impact of COVID-19 on the academic, clinical and personal experiences of healthcare students. Method Undergraduate students across three year groups within the School of Health Sciences at Ulster University completed online Qualtrics surveys at three timepoints during one academic year (2020/2021). Quantitative survey data was downloaded from Qualtrics into SPSS Version 25 for descriptive analysis of each cross-sectional sample. Qualitative survey data was downloaded into text format, which was thematically analysed using content analysis. Results 412 students completed the survey at Time 1 (October 2020), n = 309 at Time 2 (December 2020) and n = 259 at Time 3 (April 2021). Academically, the pandemic had mostly a negative impact on the learning environment, the development of practical skills, the assessment process and opportunities for peer learning and support. Students reported increased stress and challenges managing their workload and maintaining a sense of motivation and routine. Clinically, they felt unprepared by the university for placement where the pandemic had an increasingly negative impact over time on learning and skill development. In terms of personal experiences, despite the majority of students taking steps to keep physically and mentally well, negative impacts on friendships, mental wellbeing and concerns for family were reported. The pandemic had not impacted upon career choice for most students. Conclusion Consideration must be given to the development of practical skills so students feel prepared for their professional careers given the practical nature of their roles. Programme coordinators should adopt a holistic approach to student wellbeing.

Background In recent years, interest has grown in whether and to what extent demographic diversity sparks discovery and innovation in research. At the same time, topic modeling has been employed to discover differences in what women and men write about. This study engages these two strands of scholarship to explore associations between changing researcher demographics and research questions asked in the discipline of history. Specifically, we analyze developments in history as women entered the field. Methods We focus on author gender in diachronic analysis of history dissertations from 1980 (when online data is first available) to 2015 and a select set of general history journals from 1950 to 2015. We use correlated topic modeling and network visualizations to map developments in research agendas over time and to examine how women and men have contributed to these developments. Results Our summary snapshot of aggregate interests of women and men for the period 1950 to 2015 identifies new topics associated with women authors: gender and women’s history, body history, family and households, consumption and consumerism, and sexuality. Diachronic analysis demonstrates that while women pioneered topics such as gender and women’s history or the history of sexuality, these topics broaden over time to become methodological frameworks that historians widely embraced and that changed in interesting ways as men engaged with them. Our analysis of history dissertations surface correlations between advisor/advisee gender pairings and choice of dissertation topic. Conclusions Overall, this quantitative longitudinal study suggests that the growth in women historians has coincided with the broadening of research agendas and an increased sensitivity to new topics and methodologies in the field.

Background The management of patients’ holistic symptom needs are often complex and challenging. The education needs of undergraduate nursing students must be optimally addressed to have a significant positive impact on patient care. Mobile spaced learning has been recognised as a form of online education which can provide a novel approach to delivering effective evidence based healthcare education to undergraduate students. Objective The objective of this pilot study was to explore the experiences of undergraduate nursing students in a university setting, of using mobile spaced learning as a digital platform for symptom management education. Method This pilot study used a mixed methods approach. Online spaced learning material, which utilised both case based scenarios and multiple choice questions, was delivered to first year undergraduate nursing students over a period of 2 weeks. Participants were then invited to participate in an online survey related to the usability of mobile spaced learning. A focus group was conducted to further explore the participants’ views. Result Findings conveyed that students viewed mobile spaced learning as an acceptable platform that enhanced both their learning and their ability to transfer knowledge into clinical practice. Conclusion Implementation of a digital spaced learning intervention would be acceptable to undergraduate nursing students learning about holistic symptom management. Further research is needed to explore the feasibility of implementing this intervention within the undergraduate nursing curriculum, and also to explore the impact on long-term knowledge retention.

Recent models of spiking neuronal networks have been trained to perform behaviors in static environments using a variety of learning rules, with varying degrees of biological realism. Most of these models have not been tested in dynamic visual environments where models must make predictions on future states and adjust their behavior accordingly. The models using these learning rules are often treated as black boxes, with little analysis on circuit architectures and learning mechanisms supporting optimal performance. Here we developed visual/motor spiking neuronal network models and trained them to play a virtual racket-ball game using several reinforcement learning algorithms inspired by the dopaminergic reward system. We systematically investigated how different architectures and circuit-motifs (feed-forward, recurrent, feedback) contributed to learning and performance. We also developed a new biologically-inspired learning rule that significantly enhanced performance, while reducing training time. Our models included visual areas encoding game inputs and relaying the information to motor areas, which used this information to learn to move the racket to hit the ball. Neurons in the early visual area relayed information encoding object location and motion direction across the network. Neuronal association areas encoded spatial relationships between objects in the visual scene. Motor populations received inputs from visual and association areas representing the dorsal pathway. Two populations of motor neurons generated commands to move the racket up or down. Model-generated actions updated the environment and triggered reward or punishment signals that adjusted synaptic weights so that the models could learn which actions led to reward. Here we demonstrate that our biologically-plausible learning rules were effective in training spiking neuronal network models to solve problems in dynamic environments. We used our models to dissect the circuit architectures and learning rules most effective for learning. Our model shows that learning mechanisms involving different neural circuits produce similar performance in sensory-motor tasks. In biological networks, all learning mechanisms may complement one another, accelerating the learning capabilities of animals. Furthermore, this also highlights the resilience and redundancy in biological systems.

The aim of this study was to assess risk factors associated with low levels of HIV testing among MSM recruited through respondent driven sampling (RDS) in Brazil. Of 3,617 participants, 48.4% had never tested previously for HIV. A logistic model indicated that younger age, lower socioeconomic class, education, poor HIV/AIDS knowledge, no history of cruising, and having been tested during the study were characteristics independently associated with low levels of previous HIV testing. The HIV testing rate among MSM in Brazil is still low in spite of the availability of a large number services providing universal and free access to HIV/AIDS diagnosis and treatment. To respond to low utilization, the authors propose a higher priority for testing for key populations such as MSM, expanded education, expanding testing sites and a welcoming and nonjudgmental environment in health services.

BackgroundTotal sedentary time varies across population groups with important health consequences. Patterns of sedentary time accumulation may vary and have differential health risks. The purpose of this study is to describe sedentary patterns of older adults living in retirement communities and illustrate gender and age differences in those patterns.MethodsBaseline accelerometer data from 307 men and women (mean age = 84±6 years) who wore ActiGraph GT3X+ accelerometers for ≥ 4 days as part of a physical activity intervention were classified into bouts of sedentary time (

BACKGROUND: Caring for patients with multimorbidity is common for generalists, although such patients are often excluded from clinical trials, and thus such trials lack of generalizability. Data on the association between multimorbidity and preventive care are limited. We aimed to assess whether comorbidity number, severity and type were associated with preventive care among patients receiving care in Swiss University primary care settings. METHODS: We examined a retrospective cohort composed of a random sample of 1,002 patients aged 50-80 years attending four Swiss university primary care settings. Multimorbidity was defined according to the literature and the Charlson index. We assessed the quality of preventive care and cardiovascular preventive care with RANDs Quality Assessment Tool indicators. Aggregate scores of quality of provided care were calculated by taking into account the number of eligible patients for each indicator. RESULTS: Participants (mean age 63.5 years, 44% women) had a mean of 2.6 (SD 1.9) comorbidities and 67.5% had 2 or more comorbidities. The mean Charlson index was 1.8 (SD 1.9). Overall, participants received 69% of recommended preventive care and 84% of cardiovascular preventive care. Quality of care was not associated with higher numbers of comorbidities, both for preventive care and for cardiovascular preventive care. Results were similar in analyses using the Charlson index and after adjusting for age, gender, occupation, center and number of visits. Some patients may receive less preventive care including those with dementia (47%) and those with schizophrenia (35%). CONCLUSIONS: In Swiss university primary care settings, two thirds of patients had 2 or more comorbidities. The receipt of preventive and cardiovascular preventive care was not affected by comorbidity count or severity, although patients with certain comorbidities may receive lower levels of preventive care.

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.

BackgroundMotivated by the challenges in assessing physician-level cancer screening performance and the negative impact of misclassification, we propose a method (using mammography as an example) that enables confident assertion of adequate or inadequate performance or alternatively recognizes when more data is required.MethodsUsing established metrics for mammography screening performance-cancer detection rate (CDR) and recall rate (RR)-and observed benchmarks from the Breast Cancer Surveillance Consortium (BCSC), we calculate the minimum volume required to be 95% confident that a physician is performing at or above benchmark thresholds. We graphically display the minimum observed CDR and RR values required to confidently assert adequate performance over a range of interpretive volumes. We use a prospectively collected database of consecutive mammograms from a clinical screening program outside the BCSC to illustrate how this method classifies individual physician performance as volume accrues.ResultsOur analysis reveals that an annual interpretive volume of 2770 screening mammograms, above the United States' (US) mandatory (480) and average (1777) annual volumes but below England's mandatory (5000) annual volume is necessary to confidently assert that a physician performed adequately. In our analyzed US practice, a single year of data uniformly allowed confident assertion of adequate performance in terms of RR but not CDR, which required aggregation of data across more than one year.ConclusionFor individual physician quality assessment in cancer screening programs that target low incidence populations, considering imprecision in observed performance metrics due to small numbers of patients with cancer is important.

[This corrects the article DOI: 10.1371/journal.pone.0229098.].

IntroductionChild maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association between CM and later health problems. However, there are methodological inconsistencies in studies of the association between CM and systemic inflammation and findings are conflicting. We performed a systematic review to examine the association of CM with systemic inflammation in adults.MethodsA pre-registered systematic review was performed following PRISMA guidelines. Medline, Embase, Scopus and PsychInfo were searched for studies of the association of CM with blood markers of inflammation in adults. Quality was assessed using the Crowe Critical Appraisal Tool. We had intended to perform a meta-analysis, but this was not possible due to variation in study design and reporting.ResultsForty-four articles met criteria for inclusion in the review. The most widely reported biomarkers were C-Reactive Protein (CRP) (n = 27), interleukin-6 (IL-6) (n = 24) and Tumour Necrosis Factor-alpha (TNF-a) (n = 17). Three studies were prospective (all relating to CRP) and the remainder were retrospective. 86% of studies were based in high income countries. In the prospective studies, CM was associated with elevated CRP in adulthood. Results of retrospective studies were conflicting. Methodological issues relating to the construct of CM, methods of analysis, and accounting for confounding or mediating variables (particularly Body Mass Index) may contribute to the uncertainty in the field.ConclusionsThere is some robust evidence from prospective studies that CM is associated with elevated CRP in adulthood. We have identified significant methodological inconsistencies in the literature and have proposed measures that future researchers could employ to improve consistency across studies. Further prospective, longitudinal, research using robust and comparable measures of CM with careful consideration of confounding and mediating variables is required to bring clarity to this field.

Neuromedin U (NMU), a highly conserved peptide in mammals, is involved in a wide variety of physiological processes, including impairment of pancreatic β-cell function via induction of mitochondrial dysfunction and endoplasmic reticulum (ER) stress, ultimately suppressing insulin secretion. NMU has two receptors, NMU receptor 1 (NMUR1) and NMUR2, both of which are G-protein-coupled receptors (GPCRs). Only NMUR1 is expressed in mouse islets and β cell-derived MIN6-K8 cells. The molecular mechanisms underlying the insulinostatic action mediated by NMUR1 in β cells have yet to be elucidated. In this study, we explored the molecular mechanism driving impairment of insulin secretion in β cells by the NMU-NMUR1 axis. Pretreatment with the Gαi/o inhibitor Bordetella pertussis toxin (PTX), but not the Gαq inhibitor YM254890, abolished NMU-induced suppression of glucose-stimulated insulin secretion and calcium response in β cells. Knockdown of Gαi2 and Gαo in β cells counteracted NMU-induced suppression of insulin secretion and gene alterations related to mitochondrial fusion (Mfn1, Mfn2), fission (Fis1, Drp1), mitophagy (Pink1, Park2), mitochondrial dynamics (Pgc-1α, Nrf1, and Tfam), ER stress (Chop, Atp2a3, Ryr2, and Itpr2), intracellular ATP level, and mitochondrial membrane potential. NMU decreased forskolin-stimulated intracellular cAMP in both mouse and human islets. We concluded that NMUR1 coupled to PTX-sensitive Gαi2 and Gαo proteins in β cells reduced intracellular Ca2+ influx and cAMP level, thereby causing β-cell dysfunction and impairment. These results highlight a novel signaling mechanism of NMU and provide valuable insights into the further investigation of NMU functions in β-cell biology.

BackgroundViolent victimization is common among people who use illegal drugs (PWUD) and is a source of significant health-related harm. However, little attention has been paid to how antecedent childhood trauma among PWUD may contribute to the risk of victimization in adulthood.ObjectiveThis study sought to examine the relationship between childhood physical abuse and victimization by physical assault among adult PWUD.Participants and settingData were derived from three prospective cohorts of PWUD in Vancouver, Canada between 2005 and 2018.MethodsChildhood physical abuse was assessed using the Childhood Trauma Questionnaire. Generalized linear mixed modeling was used to estimate the relationship between childhood physical abuse and subsequent violent victimization, after adjustment for potential confounders.ResultsAmong 2960 PWUD, including 1018 (34.39%) female participants, 1030 (34.8%) participants reported a history of moderate to severe childhood physical abuse, and 949 (32.06%) participants reported recent violent victimization at baseline. In a multivariate analysis, childhood physical abuse (Adjusted Odds Ratio [AOR] = 1.34, 95% confidence interval [CI]: 1.23-1.46) remained independently associated with violent victimization after adjustment for potential confounders.ConclusionsThis study found a high prevalence of childhood physical abuse and that this was associated with a higher risk of subsequent violent victimization among PWUD in this setting. Greater support for PWUD with a history of childhood physical abuse is needed to decrease existing vulnerability to violence, including screening for and treatment of childhood trauma and related violence prevention.

Gestational trophoblastic disease (GTD) is a heterogeneous group of lesions arising from placental tissue. Epithelioid trophoblastic tumor (ETT), derived from chorionic-type trophoblast, is the rarest form of GTD with only approximately 130 cases described in the literature. Due to its morphologic mimicry of epithelioid smooth muscle tumors and carcinoma, ETT can be misdiagnosed. To date, molecular characterization of ETTs is lacking. Furthermore, ETT is difficult to treat when disease spreads beyond the uterus. Here using RNA-Seq analysis in a cohort of ETTs and other gestational trophoblastic lesions we describe the discovery of LPCAT1-TERT fusion transcripts that occur in ETTs and coincide with underlying genomic deletions. Through cell-growth assays we demonstrate that LPCAT1-TERT fusion proteins can positively modulate cell proliferation and therefore may represent future treatment targets. Furthermore, we demonstrate that TERT upregulation appears to be a characteristic of ETTs, even in the absence of LPCAT1-TERT fusions, and that it appears linked to copy number gains of chromosome 5. No evidence of TERT upregulation was identified in other trophoblastic lesions tested, including placental site trophoblastic tumors and placental site nodules, which are thought to be the benign chorionic-type trophoblast counterpart to ETT. These findings indicate that LPCAT1-TERT fusions and copy-number driven TERT activation may represent novel markers for ETT, with the potential to improve the diagnosis, treatment, and outcome for women with this rare form of GTD.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p

BACKGROUND:We developed, and pilot tested a family focused intervention Sammanit Jeevan "Living with Dignity" to reduce gender-based violence by husbands, change harmful social and gender norms and improve the economic conditions of women through young married women-led income generating activities (IGAs). METHODS:We conducted a modified interrupted time series study and qualitative research to evaluate the intervention in two migrant communities in Baglung district, Nepal. We enrolled young married women, their husbands and in-laws from 100 families. 200 women and 157 men completed questionnaires before the programme, and 6, 12 and 18 months afterwards. 18 in-depth interviews were conducted before the programme and 6 and 12 months later. We analysed the data for trends. RESULTS:The intervention positively impacted young married women's economic conditions, exposure to violence and changed inequitable gender attitudes. Some positive outcomes were observed among older women and men. Young women's past month earnings (35.0% - 81.3%, β = 0.11, p-value

There is a significant delay between seeking help and a confirmed diagnosis of Autism Spectrum Disorder (ASD). This delay can lead to poor outcomes for both the families and individuals. Telehealth potentially offers a way of improving the diagnostic pathway for ASD. We conducted a scoping review examining which telehealth approaches are used in the diagnosis and assessment of ASD in children and adults, whether they are feasible and acceptable, and how they compare with face-to-face diagnosis and assessment methods. A search for all peer-reviewed articles, combining the terms of autism and telehealth was conducted from 2000 to 2019. A total of 10 studies were identified for inclusion in the review. This review of the literature found there to be two methods of using telehealth: (a) Real-Time method e.g. video conferencing that enables teams in different areas to consult with the families and to assess the child/adult in real time and (b) A Store-and-Forward method as Naturalistic Observation Diagnostic Assessment (NODA) system to upload videos of child's behaviors to a webportal that enables the clinicians to make an assessment remotely. The findings were positive, finding there to be high agreement in terms of the diagnosis between remote methods and face to face methods and with high levels of satisfaction among the families and clinicians. This field is in the very early stages and so only studies with small sample size using surveys and interviews were identified but the findings suggest that there is potential for telehealth methods to improve access to assessment and diagnosis of ASD used in conjunction with existing methods, especially for those with clear autism traits and adults with ASD. Larger randomised controlled trials of this technology are warranted.

The focus of gastro-intestinal parasite control in the sheep industry is increasingly on finding a balance between maintaining productivity of the flock whilst minimising selection for anthelmintic resistance to preserve anthelmintic efficacy for the future. Periparturient ewes represent the major source of gastro-intestinal parasites for growing lambs and are therefore a priority for parasite control. This study examines the impact on ewe faecal egg counts (FECs), lamb FECs, lamb daily live weight gains (DLWGs) and pasture larval counts of treating groups of ewes two weeks prior to lambing with either, a long-acting moxidectin treatment, short-acting doramectin or control. Six groups of twenty ewes were allocated to individual paddocks, two groups allocated to each treatment, and weekly faecal sampling was performed throughout from the ewes and from six weeks after the start of lambing in the lambs. Treatment group was found to have a significant effect on both ewe FEC (p

BackgroundIt is unclear how dual-task gait influences the lower limb range of motion (RoM) in people with Parkinson's disease (PD) and freezing of gait (FOG). The lower limb kinematics during dual-task gait might differ from regular gait, but during what events in the gait cycle?MethodsThis is an observational within-subjects study. Thirty-two individuals with PD and FOG underwent a gait analysis. Single and dual-task gait was assessed by a 3D motion analysis system and the RoM data of the lower limb were extracted from hips, knees and ankles in the sagittal plane. Dual-task assignment was performed using word-color interference test. To compare both gait conditions, we used two different analyses: (1) common discrete analysis to provide lower limb RoM and (2) Statistical Parametric Mapping analysis (SPM) to provide lower limb joint kinematics. A correlation between lower limb RoM and spatiotemporal gait parameters was also performed for each gait condition.ResultsCommon discrete analysis evidenced reductions in RoM of hips, knees and ankles during the dual task gait when compared to single gait. SPM analysis showed reductions in flexion-extension of hip, knees and ankles joints when dual task was compared to single task gait. These reductions were observed in specific gait events as toe off (for knees and ankles) and heel strike (for all joints). The reduction in lower limb RoM was positively correlated with the reduction in step length and gait speed.ConclusionsLower limb joints kinematics were reduced during toe off and heel strike in dual task gait when compared to single gait. These findings might help physiotherapists to understand the influence of dual and single walking in lower limb RoM throughout the gait cycle in people with PD and FOG.

BackgroundStudies on the impacts of child maltreatment (CM) have been conducted in diverse areas. Mechanistic understanding of the complex interplay between factors is lacking. Hallmarking is an approach which identifies common factors across studies and highlights the most robust findings.ObjectivesIn a review of systematic reviews and meta-analyses, we addressed the following questions: 1) What are the hallmarks associated with exposure to CM across the bio-ecological spectrum? 2) What is the strength of evidence to support each hallmark? 3) What are the gaps that future research should address?MethodsA comprehensive literature search was carried out to find relevant systematic reviews or meta-analyses. 269 articles were read in full and 178 articles, encompassing more than 6000 original papers, were included in the final synthesis. All reviews were independently rated for quality by at least 2 reviewers using AMSTAR-2.ResultsOf 178 review articles, 6 were rated as high quality (all meta-analyses) and 46 were rated as medium quality. Most were from high income countries.ConclusionsBased on the most commonly reported high-quality research findings we propose that the hallmarks of exposure to child maltreatment are: Increased risk of psychopathology; Increased risk of obesity; Increased risk of high- risk sexual behaviours, Increased risk of smoking; and Increased risk of child maltreatment in children with disabilities. Research gaps include a lack of focus on complexity and resilience. Little can be concluded about directions of causality or mechanisms. Adequately powered prospective studies are required to move the field forward.

BackgroundCannabis use is common among marginalized people who use illicit drugs (PWUD) but reasons for use remain poorly investigated. We sought to explore how different intentions for cannabis use relate to social, structural, and behavioural factors among PWUD in Vancouver, Canada.MethodsWe used data from cannabis-using participants in two community-recruited prospective cohort studies of PWUD. Using latent class analysis, we identified discrete cannabis-using groups based on self-reported intentions for use. Generalized estimating equations were used to examine correlates of class membership.ResultsBetween June 2016 and December 2018, 2,686 observations from 897 participants cannabis-using PWUD were analyzed. Four latent classes of cannabis use emerged: Class 1 (31.6%), characterized by non-medical purposes; Class 2 (37.5%), characterized by non-pain therapeutic use (e.g., stress, nausea/loss of appetite, and insomnia); characterized by Class 3 (21.9%) predominantly pain relief; and Class 4 (9.0%), characterized by a wide range of therapeutic uses in addition to pain management, including insomnia, stress, nausea/loss of appetite, and harm reduction. Class-specific structural, substance-, and health-related differences were observed, including indicators of better physical and mental health among the "recreational" class, despite evidence of more structural vulnerabilities (e.g., homelessness, incarceration).ConclusionsOur findings demonstrate a wide spectrum of motivations for cannabis use among PWUD. We observed important health-related differences between latent classes, demonstrating possible unmet healthcare needs among PWUD reporting therapeutic cannabis use. These findings inform ongoing policy surrounding access to cannabis for harm reduction purposes and applications of medical cannabis for PWUD.

ObjectivesOral potentially malignant disorders (OPMDs) encompass histologically benign, dysplastic, and cancerous lesions that are often indistinguishable by appearance and inconsistently managed. We assessed the potential impact of test-and-treat pathways enabled by a point-of-care test for OPMD characterization.Materials and methodsWe constructed a decision-analytic model to compare life expectancy of test-treat strategies for 60-year-old patients with OPMDs in the primary dental setting, based on a trial for a point-of-care cytopathology tool (POCOCT). Eight strategies of OPMD detection and evaluation were compared, involving deferred evaluation (no further characterization), prompt OPMD characterization using POCOCT measurements, or the commonly recommended usual care strategy of routine referral for scalpel biopsy. POCOCT pathways differed in threshold for additional intervention, including surgery for any dysplasia or malignancy, or for only moderate or severe dysplasia or cancer. Strategies with initial referral for biopsy also reflected varied treatment thresholds in current practice between surgery and surveillance of mild dysplasia. Sensitivity analysis was performed to assess the impact of variation in parameter values on model results.ResultsRequisite referral for scalpel biopsy offered the highest life expectancy of 20.92 life-years compared with deferred evaluation (+0.30 life-years), though this outcome was driven by baseline assumptions of limited patient adherence to surveillance using POCOCT. POCOCT characterization and surveillance offered only 0.02 life-years less than the most biopsy-intensive strategy, while resulting in 27% fewer biopsies. When the probability of adherence to surveillance and confirmatory biopsy was ≥ 0.88, or when metastasis rates were lower than reported, POCOCT characterization extended life-years (+0.04 life-years) than prompt specialist referral.ConclusionRisk-based OPMD management through point-of-care cytology may offer a reasonable alternative to routine referral for specialist evaluation and scalpel biopsy, with far fewer biopsies. In patients who adhere to surveillance protocols, POCOCT surveillance may extend life expectancy beyond biopsy and follow up visual-tactile inspection.

Non-communicable diseases, including cardiovascular diseases (CVDs), are increasing in African populations. High serum low density lipoprotein cholesterol (LDL-cholesterol) levels are a known risk factor for CVDs in European populations, but the link remains poorly understood among Africans. This study investigated the associations between serum LDL-cholesterol levels and selected variants in the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and low density lipoprotein receptor adaptor protein 1 (LDLRAP1) genes in some selected African populations. Nineteen SNPs were selected from publicly available African whole genome sequence data based on functional prediction and allele frequency. SNPs were genotyped in 1000 participants from the AWI-Gen, study selected from the extremes of LDL-cholesterol level distribution (500 with LDL-cholesterol>3.5 mmol/L and 500 with LDL-cholesterol

Biomarkers can be used to enrich a clinical trial for patients at higher risk for an outcome, a strategy termed "prognostic enrichment." Methodology is needed to evaluate biomarkers for prognostic enrichment of trials with time-to-event endpoints such as survival. Key considerations when considering prognostic enrichment include: clinical trial sample size; the number of patients one must screen to enroll the trial; and total patient screening costs and total per-patient trial costs. The Biomarker Prognostic Enrichment Tool for Survival Outcomes (BioPETsurv) is a suite of methods for estimating these elements to evaluate a prognostic enrichment biomarker and/or plan a prognostically enriched clinical trial with a time-to-event primary endpoint. BioPETsurv allows investigators to analyze data on a candidate biomarker and potentially censored survival times. Alternatively, BioPETsurv can simulate data to match a particular clinical setting. BioPETsurv's data simulator enables investigators to explore the potential utility of a prognostic enrichment biomarker for their clinical setting. Results demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics such as reducing sample size or trial costs. In addition to the quantitative analysis provided by BioPETsurv, investigators should consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria. BioPETsurv is freely available as a package for the R statistical computing platform, and as a webtool at www.prognosticenrichment.com/surv.