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Introduction This study sought to examine reasons for youth e-cigarette use in association with vaping patterns and cessation behaviors. Aims and Methods A national representative sample of current (past 30-day) e-cigarette users in grades 6–12 was analyzed using the National Youth Tobacco Survey (NYTS), conducted from January to March 2020. An exploratory oblique factor analysis using a rotated pattern matrix to select salient variable-factor relationships yielded four subscales related to reasons for youth e-cigarette use. Multivariate logistic regressions were performed to assess the associations of each subscale with vaping patterns (frequent e-cigarette use, dual use of e-cigarettes and other tobacco products) and vaping cessation behaviors (intention to quit vaping and past-year quit attempts). Results The 2020 NYTS sampled 180 schools with 1769 current e-cigarette users. Four main reasons for vaping were identified through factor analysis, including (1) replacing cigarettes, (2) product characteristics [eg, flavors, concealability, and vape tricks], (3) family/friend use, and (4) curiosity. Curiosity was associated with lower odds of frequent e-cigarette use (adjusted odds ratio [AOR] = 0.5, p < .0001) and dual use of e-cigarettes and other tobacco products (AOR = 0.6, p = .01) but higher odds of intention to quit (AOR = 1.2, p = .26) and past year quit attempts (AOR =1.5, p = .01). Vaping due to product characteristics was associated with higher odds of frequent e-cigarette use (AOR = 1.7, p < .0001) and lower odds of intention to quit (AOR = 0.3, p < .0001) and past year quit attempts (AOR = 0.9, p = .01). Conclusions Adolescents vape for various reasons that follow distinct patterns and user characteristics. Overall, interventions tailored to address heterogeneous reasons for vaping may help optimize the reduction in youth e-cigarette use. Implications E-cigarettes have surpassed cigarettes and become the most commonly used tobacco product by US youths. Adolescents choose to vape for different reasons. This study examined reasons for youth e-cigarette use and their associations with vaping patterns and cessation behaviors. The product characteristics factor (eg, flavors, concealability, and vape tricks) was associated with more frequent e-cigarette use and lower odds of cessation behaviors, suggesting a need for flavor bans and product design regulation.

Chronic insomnia affects ∼25% of young adult cancer survivors (YACS) but is often overlooked in routine follow-up. A recently introduced three-item version of the Insomnia Severity Index (ISI-3) was compared with a diagnostic interview (SCID-5) in 250 YACS (ages 18-40) to evaluate its validity in this population. The ISI-3 had good discrimination compared with the SCID-5 (area under the receiver operating characteristic curve = 0.88). Although no ISI-3 cutoff met study criteria for both sensitivity (≥0.85) and specificity (≥0.75), an ISI-3 cutoff of ≥4 had high sensitivity (94%) and moderate specificity (70%), and is recommended as the first step in a two-step screening procedure.

BackgroundPulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects delineate the PDAC syndrome. We aim to identify the cause of PDAC syndrome in patients who do not carry pathogenic variants inRARBandSTRA6, which have been previously associated with this disorder.MethodsWe sequenced the exome of patients with unexplained PDAC syndrome and performed functional validation of candidate variants.ResultsWe identified bi-allelic variants inWNT7Bin fetuses with PDAC syndrome from two unrelated families. In one family, the fetus was homozygous for the c.292C>T (p.(Arg98*)) variant whereas the fetuses from the other family were compound heterozygous for the variants c.225C>G (p.(Tyr75*)) and c.562G>A (p.(Gly188Ser)). Finally, a molecular autopsy by proxy in a consanguineous couple that lost two babies due to lung hypoplasia revealed that both parents carry the p.(Arg98*) variant. Using a WNT signalling canonical luciferase assay, we demonstrated that the identified variants are deleterious. In addition, we found thatwnt7bbmutant zebrafish display a defect of the swimbladder, an air-filled organ that is a structural homolog of the mammalian lung, suggesting that the function of WNT7B has been conserved during evolution for the development of these structures.ConclusionOur findings indicate that defective WNT7B function underlies a form of lung hypoplasia that is associated with the PDAC syndrome, and provide evidence for involvement of the WNT–β-catenin pathway in human lung, tracheal, ocular, cardiac, and renal development.

Background: The relevance of social support for weight management is not well documented in people with prediabetes. An important consideration is the adequate assessment of social provisions related to weight management in this population. Purpose: To assess the factor structure and measurement invariance of an adapted Social Provisions Scale specific to weight management (SPS-WM). Methods: Participants of a diabetes prevention trial (n=599) completed a demographic survey, and the SPS-WM. Confirmatory analyses tested the factor structure of the SPS-WM, and measurement invariance was assessed for gender, weight status, education level, and age. Results: Removal of two collinear items resulted in acceptable model fit, supporting six correlated factors for social provisions specific to weight management. Measurement invariance was supported across all subgroups. Conclusion: Results support score interpretations for these scales reflecting distinct components of social support specific to weight management in alignment with those of the original survey.

'Supplementary Table S2- Somatic mutations identified in the tumors from individuals III.6; III.7 and III.8 in family 1 and individual III.1 in family 2 among 193 DNA repair genes.'

This file includes supplementary Figure S1, Supplementary Figure S2 and Supplementary Figure S3. It also includes Supplementary Table S1 - RAD51D c.620C

'Supplementary Table3 -Presence of allelic imbalanced alleles in RAD51D and TP53 somatic mutations in RAD51D c.620C>T;p.S207L HGSC carriers.'

RAD51D is a key player in DNA repair by homologous recombination (HR), and RAD51D truncating variant carriers have an increased risk for ovarian cancer. However, the contribution of nontruncating RAD51D variants to cancer predisposition remains uncertain. Using deep sequencing and case–control genotyping studies, we show that in French Canadians, the missense RAD51D variant c.620C>T;p.S207L is highly prevalent and is associated with a significantly increased risk for ovarian high-grade serous carcinoma (HGSC; 3.8% cases vs. 0.2% controls). The frequency of the p.S207L variant did not significantly differ from that of controls in breast, endometrial, pancreas, or colorectal adenocarcinomas. Functionally, we show that this mutation impairs HR by disrupting the RAD51D–XRCC2 interaction and confers PARP inhibitor sensitivity. These results highlight the importance of a functional RAD51D–XRCC2 interaction to promote HR and prevent the development of HGSC. This study identifies c.620C>T;p.S207L as the first bona fide pathogenic RAD51D missense cancer susceptibility allele and supports the use of targeted PARP-inhibitor therapies in ovarian cancer patients carrying deleterious missense RAD51D variants. Cancer Res; 77(16); 4517–29. ©2017 AACR.

Although technology-assisted diabetes prevention programs (DPPs) have been shown to improve glycemic control and weight loss, information are limited regarding relevant costs and their cost-effectiveness. To describe a retrospective within-trial cost and cost-effectiveness analysis (CEA) to compare a digital-based DPP (d-DPP) with small group education (SGE), over a 1-year study period. The costs were summarized into direct medical costs, direct nonmedical costs (i.e., times that participants spent engaging with the interventions), and indirect costs (i.e., lost work productivity costs). The CEA was measured by the incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed using nonparametric bootstrap analysis. Over 1 year, the direct medical costs, direct nonmedical costs, and indirect costs per participant were $4,556, $1,595, and $6,942 in the d-DPP group versus $4,177, $1,350, and $9,204 in the SGE group. The CEA results showed cost savings from d-DPP relative to SGE based on a societal perspective. Using a private payer perspective for d-DPP, ICERs were $4,739 and $114 to obtain an additional unit reduction in HbA1c (%) and weight (kg), and were $19,955 for an additional unit gain of quality-adjusted life years (QALYs) compared to SGE, respectively. From a societal perspective, bootstrapping results indicated that d-DPP has a 39% and a 69% probability, at a willingness-to-pay of $50,000/QALY and $100,000/QALY, respectively, of being cost-effective. The d-DPP was cost-effective and offers the prospect of high scalability and sustainability due to its program features and delivery modes, which can be easily translated to other settings.

Bain type of X-linked syndromic intellectual developmental disorder, caused by pathogenic missense variants in HRNRPH2, was initially described in six female individuals affected by moderate-to-severe neurodevelopmental delay. Although it was initially postulated that the condition would not be compatible with life in males, several affected male individuals harboring pathogenic variants in HNRNPH2 have since been documented. However, functional in-vitro analyses of identified variants have not been performed and, therefore, possible genotype–phenotype correlations remain elusive. Here, we present eight male individuals, including a pair of monozygotic twins, harboring pathogenic or likely pathogenic HNRNPH2 variants. Notably, we present the first individuals harboring nonsense or frameshift variants who, similarly to an individual harboring a de novo p.(Arg29Cys) variant within the first quasi-RNA-recognition motif (qRRM), displayed mild developmental delay, and developed mostly autistic features and/or psychiatric co-morbidities. Additionally, we present two individuals harboring a recurrent de novo p.(Arg114Trp), within the second qRRM, who had a severe neurodevelopmental delay with seizures. Functional characterization of the three most common HNRNPH2 missense variants revealed dysfunctional nucleocytoplasmic shuttling of proteins harboring the p.(Arg206Gln) and p.(Pro209Leu) variants, located within the nuclear localization signal, whereas proteins with p.(Arg114Trp) showed reduced interaction with members of the large assembly of splicing regulators (LASR). Moreover, RNA-sequencing of primary fibroblasts of the individual harboring the p.(Arg114Trp) revealed substantial alterations in the regulation of alternative splicing along with global transcriptome changes. Thus, we further expand the clinical and variant spectrum in HNRNPH2-associated disease in males and provide novel molecular insights suggesting the disorder to be a spliceopathy on the molecular level.

Amongst the numerous genes associated with intellectual disability, SYNGAP1 stands out for its frequency and penetrance of loss-of-function variants found in patients, as well as the wide range of co-morbid disorders associated with its mutation. Most studies exploring the pathophysiological alterations caused by Syngap1 haploinsufficiency in mouse models have focused on cognitive problems and epilepsy, however whether and to what extent sensory perception and processing are altered by Syngap1 haploinsufficiency is less clear. By performing EEG recordings in awake mice, we identified specific alterations in multiple aspects of auditory and visual processing, including increased baseline gamma oscillation power, increased theta/gamma phase amplitude coupling following stimulus presentation and abnormal neural entrainment in response to different sensory modality-specific frequencies. We also report lack of habituation to repetitive auditory stimuli and abnormal deviant sound detection. Interestingly, we found that most of these alterations are present in human patients as well, thus making them strong candidates as translational biomarkers of sensory-processing alterations associated with SYNGAP1/Syngap1 haploinsufficiency.

Background Both theoretical and empirical evidence supports the potential of modest financial incentives to increase the reach of evidence-based weight control programs. However, few studies exist that examine the best incentive design for achieving the highest reach and representativeness at the lowest cost and whether or not incentive designs may be valued differentially by subgroups that experience obesity-related health disparities. Methods A discrete choice experiment was conducted (n = 1232 participants; over 90% of them were overweight/obese) to collect stated preference towards different financial incentive attributes, including reward amount, program location, reward contingency, and payment form and frequency. Mixed logit and conditional logit models were used to determine overall and subgroup preference ranking of attributes. Using the National Health and Nutrition Examination Survey data sample weights and the estimated models, we predicted US nationally representative participation rates by subgroups and examined the effect of offering more than one incentive design. External validity was checked by using a completed cluster randomized control trial. Results There were significant subgroup differences in preference toward incentive attributes. There was also a sizable negative response to larger incentive amounts among African Americans, suggesting that higher amounts would reduce participation from this population. We also find that offering participants a menu of incentive designs to choose from would increase reach more than offering higher reward amounts. Conclusions We confirmed the existence of preference heterogeneity and the importance of subgroup-targeted incentive designs in any evidence-based weight control program to maximize population reach and reduce health disparities. National Heart, Lung, and Blood Institute of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [1R21HL097308-01A2] Published version Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number 1R21HL097308-01A2. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsoring agencies.

Objective Altered sensory processing is common in intellectual disability (ID). Here, we study electroencephalographic responses to auditory stimulation in human subjects presenting a rare condition (mutations in SYNGAP1) which causes ID, epilepsy and autism. Methods Auditory evoked potentials, time-frequency and inter-trial coherence analyses were used to compare subjects with SYNGAP1 mutations with Down syndrome (DS) and neurotypical (NT) participants (N = 61 ranging from three to 19 years of age). Results Altered synchronization in the brain responses to sound were found in both ID groups. The SYNGAP1 mutations group showed less phase-locking in early time windows and lower frequency bands compared to NT, and in later time windows compared to NT and DS. Time-frequency analysis showed more power in beta-gamma in the SYNGAP1 group compared to NT participants. Conclusions This study indicated reduced synchronization as well as more high frequencies power in SYNGAP1 mutations, while maintained synchronization was found in the DS group. These results might reflect dysfunctional sensory information processing caused by excitation/inhibition imbalance, or an imperfect compensatory mechanism in SYNGAP1 mutations individuals. Significance Our study is the first to reveal brain response abnormalities in auditory sensory processing in SYNGAP1 mutations individuals, that are distinct from DS, another ID condition.

Background Limited research has reported the economic feasibility—from both a research and practice perspective—of efforts to recruit and enroll an intended audience in evidence-based approaches for disease prevention. This study aims to retrospectively assess and estimate the costs of a population health management (PHM) approach to identify, engage, and enroll patients in a Type 1 Hybrid Effectiveness-Implementation (HEI), diabetes-prevention trial. Methods We used descriptive analyses and activity-based costing to estimate the recruitment costs of a PHM approach integrated within a HEI trial. Measures included total costs and costs per participant screened and enrolled to ensure trial accrual rates were achieved. We took the perspective of a healthcare system which may adopt, and possibly sustain, the strategy in the typical practice. We also estimated replication costs based on how the strategy could be applied in healthcare systems interested in referring patients to a local diabetes prevention program from a payer perspective. In this case, we examined differences in cost based on requirements for and types of, glucose testing, and by labor activities and non-labor resources associated with recruitment using sensitivity analyses. Results The total recruitment and enrollment costs were $389,949 to accrue 599 participants over approximately 15 months. The average cost per screened and enrolled participant was $276 and $651, respectively. Primary costs included hemoglobin A1c testing ($83,106), recruitment screening calls ($48,791), and personnel time ($96,187). Translating to the typical settings, total recruitment costs for replication was estimated as $192,625 (range: $42,523-$208,876). Sensitivity analysis results indicated replication costs would be approximately $229 - $430 per patient enrolled if glucose testing was necessary, based on the Medicare covered services. For a private payer perspective, and without glucose testing, per-participant screening and enrollment costs were estimated at $30. Conclusions A PHM approach can be used to accrue a large number of participants in a short period of time for an HEI trial, at a comparable cost per participant. However, when trial requirements are removed and PHM approaches are used as a method for healthcare systems to identify and enroll patients in a local program—the costs are relatively low.

Instrumental (operant) behavior can be goal directed, but after extended practice it can become a habit triggered by environmental stimuli. There is little information, however, about the variables that encourage habit learning, or about the development of discriminated habits that are actually triggered by specific stimuli. (Most studies of habit in animal learning have used free-operant methods.) In the present experiments, rats received training in which a lever press was reinforced only in the presence of a discrete stimulus (S) and the status of the behavior as goal-directed or habitual was determined by reinforcer devaluation tests. Experiment 1 compared lever insertion and an auditory cue (tone) in their ability to support habit learning. Despite prior speculation in the literature, the "salient" lever insertion S was not better than the tone at supporting habit, although the rats learned more rapidly to respond in its presence. Experiment 2 then examined the role of reinforcer predictability with the brief (6-s) tone S. Lever pressing during the tone was reinforced on either every trial or on 50% of trials; habit was observed only with the highly predictable (100%) relationship between S and the reinforcer. Experiment 3 replicated this effect with the tone in a modified procedure and found that lever insertion contrastingly encouraged habit regardless of reinforcer predictability. The results support an interactive role for reinforcer predictability and stimulus salience in discriminated habit learning. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

SYNGAP1haploinsufficiency in humans causes intellectual disability (ID). SYNGAP1 is highly expressed in cortical excitatory neurons and, reducing its expression in mice accelerates the maturation of excitatory synapses during sensitive developmental periods, restricts the critical period window for plasticity, and impairs cognition. However, its specific role in interneurons remains largely undetermined. In this study, we investigated the effects of conditionalSyngap1disruption in medial ganglionic eminence (MGE)-derived interneurons on hippocampal interneuron firing properties and excitatory synaptic inputs, as well as on pyramidal cell synaptic inhibition and synaptic integration. We show that conditionalSyngap1disruption in MGE-derived interneurons results in cell-specific impairment of firing properties of hippocampal Nkx2.1 fast-spiking interneurons, with enhancement of their AMPA receptor (AMPAR)-mediated excitatory synaptic inputs but compromised short-term plasticity. In contrast, regular-spiking Nkx2.1 interneurons are largely unaffected. These changes are associated with impaired pyramidal cell synaptic inhibition and enhanced summation of excitatory responses. Unexpectedly, we found that theSyngap1floxallele used in this study contains inverted loxP sites and that its targeted recombination in MGE-derived interneurons induces some cell loss during embryonic development and the reversible inversion of the sequence flanked by the loxP sites in postmitotic cells. Together, these results suggest thatSyngap1plays a role in cell-specific regulation of hippocampal interneuron function and inhibition of pyramidal cells in mice. However, because of our finding that theSyngap1floxallele used in this study contains inverted loxP sites, it will be important to further investigate interneuron function using a differentSyngap1conditional allele.

Purpose: Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12. Methods: We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids. Results: We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators’ recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment. Conclusion: Our study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity.

Introduction: Despite growing documentation of the efficacy of telemedicine in diabetes management, racial disparities in telemedicine-facilitated diabetes management remain underexplored. This study examined disparities in diabetes management outcomes between black and white patients with type 2 diabetes (T2D) in a remote monitoring program. Methods: The analysis sample included 914 white T2D patients and 365 black T2D patients in Nebraska who completed a 3-month remote patient monitoring and coaching after hospital discharge from 2014 to 2017. Ordinary least squares regression was estimated to examine racial differences in hemoglobin A1c (HbA1c), and logistic regression was used to determine the odds of HbA1c > 9% at the end of the program, controlling for demographics, baseline health conditions, and patient activation and engagement with the program. Results: The proportion of white patients with HbA1c > 9% was reduced from 16% at the baseline to 7% at program completion, and the corresponding reduction among black patients was from 30% to 18%. After adjusting for the effects of baseline HbA1c and other covariates, the average HbA1c among black patients at the end of the program was 0.23 points higher than that among white patients (p 9% was 1.68 times that of white patients (95% confidence interval [1.07-2.63]). Discussion: The remote patient monitoring and coaching program reduced the absolute gap between black and white T2D patients. However, substantial racial disparities in HbA1c still remained at the end of the program and warranted further research.

ObjectivesTo identify existing evidence concerning the cost of dissemination and implementation (D&I) strategies in community, public health and health service research, mapped with the ‘Expert Recommendations for Implementing Change’ (ERIC) taxonomy.DesignScoping review.Data sourcesMEDLINE, EMBASE, CINAHL, PsycINFO, Scopus and the Cochrane Library were searched to identify any English language reports that had been published between January 2008 and December 2019 concerning the cost of D&I strategies.Data extractionWe matched the strategies identified in each article using ERIC taxonomies; further classified them into five areas (eg, dissemination, implementation, integration, capacity building and scale-up); and extracted the corresponding costs (total costs and cots per action target and per evidence-based programme (EBP) participant). We also recorded the reported level of costing methodology used for cost assessment of D&I strategies.ResultsOf the 6445 articles identified, 52 studies were eligible for data extraction. Lack of D&I strategy cost data was the predominant reason (55% of the excluded studies) for study exclusion. Predominant topic, setting, country and research design in the included studies were mental health (19%), primary care settings (44%), the US (35%) and observational (42%). Thirty-five (67%) studies used multicomponent D&I strategies (ranging from two to five discrete strategies). The most frequently applied strategies were Conduct ongoing training (50%) and Conduct educational meetings (23%). Adoption (42%) and reach (27%) were the two most frequently assessed outcomes. The overall costs of Conduct ongoing training ranged from $199 to $105 772 ($1–$13 973 per action target and $0.02–$412 per EBP participant); whereas the cost of Conduct educational meetings ranged from $987 to $1.1–$2.9 million/year ($33–$54 869 per action target and $0.2–$146 per EBP participant). The wide range of costs was due to the varying scales of the studies, intended audiences/diseases and the complexities of the strategy components. Most studies presented limited information on costing methodology, making interpretation difficult.ConclusionsThe quantity of published D&I strategy cost analyses is increasing, yet guidance on conducting and reporting of D&I strategy cost analysis is necessary to facilitate and promote the application of comparative economic evaluation in the field of D&I research.

The primary function of the patient portal is to give patients greater access to their personal health information. Granting patients electronic access allows them to make well-informed health care decisions. This study aimed to identify sociodemographic differences in patient portal use and examine factors affecting patient portal utilization following the final stage of the Meaningful Use program which aimed to promote the use of certified electronic health record (EHR) technology. Survey data from Health Information National Trends Survey (HINTS) 5, cycles 1, 2, and 3 were analyzed. The sample included 8291 completed surveys. Multivariable logistic regression on a selected response for each surveyed question was used to assess the racial and ethnic difference after controlling for age, sex, income, and education. Subjects included English and Spanish speaking adults in the USA. Measures included assessment of patient portal use, patient portal access, understanding health information, usefulness of health records, and privacy and security. After adjusting for age, sex, income, and education, there was a significant association between race/ethnicity and patient portal non-users responding, “no need to use online medical record” as the reason for not using the patient portal (P = 0.005). Among the portal users, there were significant associations between race/ethnicity and health care provider maintaining an EHR (P = 0.006), being offered access to their portal (P

The United States is changing demographically, and Hispanics/Latinos are the largest minority group in the country. Often, Hispanics/Latinos are the driving force behind population stabilization an...

Background: Evidence-based guidelines for the management of type 2 diabetes (T2D) consist of blood glucose monitoring, medication adherence, and lifestyle modifications that may particularly benefit from reminders, consultation, education, and behavioral reinforcements through remote patient monitoring (RPM). Objectives: To identify predictors of weight loss and to examine the association between weight loss and hemoglobin A1C (HbA1C) outcomes for T2D patients who were enrolled in an RPM program for diabetes management. Materials and Methods: The study applied logistic and ordinary least-squares regression models to examine the relationship between baseline characteristics and the likelihood of weight loss during the RPM, and how the magnitude of weight loss was related to changes in HbA1C outcomes for 1,103 T2D patients who went through 3 months of RPM from 2014 to 2017. Results: Older patients were 3% more likely to have weight loss (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.05), whereas patients with higher baseline HbA1C had 9% reduced odds (OR, 0.91; 95% CI, 0.85-0.97) of experiencing weight loss. For every pound of weight lost, there was a 0.02-point (95% CI, 0.01-0.03) reduction on the HbA1C measured at the end of the RPM. Moreover, compared with those who had weight loss of ≤3%, participants who had lost 5-7%, or >7% of their baseline weight had a 0.37- and 0.58-point reduction in HbA1C, respectively. Conclusions: This study revealed a notable relationship between weight loss and positive HbA1C outcomes for T2D patients in an RPM-facilitated diabetes management program, which pointed to the potential of integrating evidence-based lifestyle modification programs into future telemedicine programs to improve diabetes management outcomes.

Advances in genomics have transformed our ability to identify the genetic causes of rare diseases (RDs), yet we have a limited understanding of the mechanistic roles of most genes in health and disease. When a novel RD gene is first discovered, there is minimal insight into its biological function, the pathogenic mechanisms of disease-causing variants, and how therapy might be approached. To address this gap, the Canadian Rare Diseases Models and Mechanisms (RDMM) Network was established to connect clinicians discovering new disease genes with Canadian scientists able to study equivalent genes and pathways in model organisms (MOs). The Network is built around a registry of more than 500 Canadian MO scientists, representing expertise for over 7,500 human genes. RDMM uses a committee process to identify and evaluate clinician-MO scientist collaborations and approve 25,000 Canadian dollars in catalyst funding. To date, we have made 85 clinician-MO scientist connections and funded 105 projects. These collaborations help confirm variant pathogenicity and unravel the molecular mechanisms of RD, and also test novel therapies and lead to long-term collaborations. To expand the impact and reach of this model, we made the RDMM Registry open-source, portable, and customizable, and we freely share our committee structures and processes. We are currently working with emerging networks in Europe, Australia, and Japan to link international RDMM networks and registries and enable matches across borders. We will continue to create meaningful collaborations, generate knowledge, and advance RD research locally and globally for the benefit of patients and families living with RD.

Objectives: Migrant farmworkers face many hardships in both their working and living environments including dangerous and demanding tasks, long hours, and inadequate rest. This study sought to expl...

The reach (i.e., enrollment, engagement, and retention) of health promotion evidence-based programs (EBPs) at the participant level has been challenging. Incentives based on behavioral economics may be used to improve EBP reach. We aimed to systematically review and synthesize the evidence of the effectiveness of incentives as a dissemination strategy to increase EBP reach. We conducted a literature search in PubMed, SCOPUS, EMBASE, Cochrane Review and Cochrane CENTRAL for articles published between January 2000 and March 2020 to identify incentive strategies used to increase program reach among health promotion EBPs. Inclusion criteria included studies published in English, experimental or quasi-experimental designs, comparison of incentive to non-incentive or control strategies, and reported on reach (n = 35 health promotion studies). Monetary incentives using cash and a fixed schedule of reinforcement were the most used incentive schemes (71%). Incentives alone or combined with other strategies as a multicomponent approach were effective in improving program enrollment, engagement, and retention. Specifically, incentive strategies were associated with higher odds of program enrollment (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.82-4.24; n = 10) and retention (OR, 2.54, 95% CI, 1.34-4.85; n = 9) with considerable heterogeneity (I

Exposure to E-cigarette marketing and media advertisements is prevalent among adolescents. A validated vaping media literacy scale is needed to inform effective vaping prevention programs.A 6-item vaping media literacy scale was adapted from validated smoking and general media literacy scales with an emphasis on marketing influences. A school-based survey (N=856) was conducted to assess the reliability of vaping media literacy and 3 subscales (i.e., authors and audiences [vaping Authors and Audiences], messages and meanings [vaping Messages and Meanings], and representation and reality [vaping Representation and Reality]). Multivariable logistic regression models were performed to examine the associations of vaping media literacy with perceived harmfulness of E-cigarette use and susceptibility to use E-cigarettes. Analyses were conducted in 2021.The mean vaping media literacy among students was 2.6 (range=0-6). There were significant disparities with lower vaping media literacy among middle-school (versus high-school, p=0.03) students, males (versus females, p=0.003), and racial/ethnic minority students (Blacks, Hispanics, others versus Whites, p=0.0009). A higher vaping media literacy was significantly associated with increased perceived harmfulness of E-cigarette use (AOR=1.2; 95% CI=1.1, 1.2; p0.0001). All subscales were also associated with E-cigarette harm perception. Among never E-cigarette users, students with a higher (versus those with a lower) vaping media literacy had lower susceptibility to initiating E-cigarettes (AOR=0.90; 95% CI=0.83, 0.97; p=0.005). Both vaping Messages and Meanings and vaping Representation and Reality subscales were adversely associated with susceptibility to vaping.The vaping media literacy scale may gauge the influence of E-cigarette marketing on adolescents with high reliability and validity. Racial minorities, younger adolescents, and males appear relatively vulnerable to vaping marketing influence. Efforts to increase vaping media literacy are needed to curb youth E-cigarette use.

The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing neurons critical for feeding regulation. Sim1 haploinsufficiency results in hyperphagic obesity with disruption of PVH neurons, yet the molecular profiles of PVH neurons and the mechanism underlying the defects of Sim1 haploinsufficiency are not well understood. By single-cell RNA sequencing, we identified two major populations of Sim1+ PVH neurons, which are differentially affected by Sim1 haploinsufficiency. The Iroquois homeobox genes Irx3 and Irx5 have been implicated in the hypothalamic control of energy homeostasis. We found that Irx3 and Irx5 are ectopically expressed in the Sim1+ PVH cells of Sim1+/− mice. By reducing their dosage and PVH-specific deletion of Irx3, we demonstrate that misexpression of Irx3 and Irx5 contributes to the defects of Sim1+/− mice. Our results illustrate abnormal hypothalamic activities of Irx3 and Irx5 as a central mechanism disrupting PVH development and feeding regulation in Sim1 haploinsufficiency.

Description, Irx3 and Irx5 misexpression in paraventricular nucleus of the hypothalamus leads to hyperphagic obesity in Sim1 haploinsufficiency., The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing neurons critical for feeding regulation. Sim1 haploinsufficiency results in hyperphagic obesity with disruption of PVH neurons, yet the molecular profiles of PVH neurons and the mechanism underlying the defects of Sim1 haploinsufficiency are not well understood. By single-cell RNA sequencing, we identified two major populations of Sim1+ PVH neurons, which are differentially affected by Sim1 haploinsufficiency. The Iroquois homeobox genes Irx3 and Irx5 have been implicated in the hypothalamic control of energy homeostasis. We found that Irx3 and Irx5 are ectopically expressed in the Sim1+ PVH cells of Sim1+/− mice. By reducing their dosage and PVH-specific deletion of Irx3, we demonstrate that misexpression of Irx3 and Irx5 contributes to the defects of Sim1+/− mice. Our results illustrate abnormal hypothalamic activities of Irx3 and Irx5 as a central mechanism disrupting PVH development and feeding regulation in Sim1 haploinsufficiency.

Background: The relevance of social support for weight management is not well documented in people with prediabetes. An important consideration is the adequate assessment of social provisions related to weight management in this population.Purpose: To assess the factor structure and measurement invariance of an adapted Social Provisions Scale specific to weight management (SPS-WM) in adults with prediabetes (n=599).Methods: Participants of a diabetes prevention trial completed a demographic survey, and the SPS-WM. Confirmatory analyses tested the factor structure of the SPS-WM, and measurement invariance was assessed for gender, weight status, education level, and age.Results: Removal of two collinear items resulted in acceptable model fit, supporting six correlated factors for social provisions specific to weight management. Measurement invariance was supported across all subgroups.Conclusion: Results support score interpretations for these scales reflecting distinct components of social support specific to weight management in alignment with those of the original survey.

Background: Several family-based efficacious pediatric weight management interventions (PWMIs) have been developed to reduce child weight status. These programs are typically based in larger cities...

Neonatal progeroid syndrome, also known as Wiedemann–Rautenstrauch syndrome, is a rare condition characterized by severe growth retardation, apparent macrocephaly with prominent scalp veins, and lipodystrophy. It is caused by biallelic variants in POLR3A, a gene encoding for a subunit of RNA polymerase III. All variants reported in the literature lead to at least a partial loss-of-function (when considering both alleles together). Here, we describe an individual with several clinical features of neonatal progeroid syndrome in whom exome sequencing revealed a homozygous nonsense variant in POLR3GL (NM_032305.2:c.358C>T; p.(Arg120Ter)). POLR3GL also encodes a subunit of RNA polymerase III and has recently been associated with endosteal hyperostosis and oligodontia in three patients with a phenotype distinct from the patient described here. Given the important role of POLR3GL in the same complex as the protein implicated in neonatal progeroid syndrome, the nature of the variant identified, our RNA studies suggesting nonsense-mediated decay, and the clinical overlap, we propose POLR3GL as a gene causing a variant of neonatal progeroid syndrome and therefore expand the phenotype associated with POLR3GL variants.