Explore the vast range of titles available.

Background Adolescent substance use has long been a top public health priority. In Indiana, concerning recent trends show high rates of youth alcohol consumption coupled with increasing use of opioids, synthetic marijuana, and over-the-counter drugs. Based on research indicating that parent-based prevention efforts may be a particularly effective way to target adolescent substance use, and in a direct effort to address Indiana’s 2017 Strategic Plan to Address Substance Use, we conducted an applied research study targeting parents’ knowledge regarding adolescent substance use in Indiana. Methods This community-based applied research study included: (i) a needs assessment of Indiana Extension Educators’ concerns regarding adolescent substance use, (ii) creation and dissemination of an evidence-informed parent education program on adolescent substance use in collaboration with Purdue Extension (a key community stakeholder), and (iii) qualitative focus group discussions at the end of each program that assessed the challenges families face regarding adolescent substance use, the types of information and resources they wish they had, and the usefulness of our program. Results The needs assessment revealed that Indiana communities would most benefit from education regarding ways to spot and monitor substance use in teens, and strategies to communicate with teens about substance use. Additionally, Extension Educators thought that existing resources to tackle substance use largely did not match the needs of Indiana communities. Qualitative analysis of the focus group discussions across 8 pilot programs revealed five important themes: (1) The need for current, evidence-informed information regarding adolescent substance use among parents and youth-involved professionals in Indiana, (2) Concern regarding Indiana adolescents’ ease of access to substances and lack of healthy recreational activities, (3) Communicating with teens about substance use is crucial but difficult to implement, (4) Indiana communities’ need to prioritize funding for evidence-informed prevention programming, and (5) The need for community-based parent and caregiver support groups. Conclusions Overall, the program was well-received and participants indicated that there was a strong need for this programming in their communities, but suggested collaborating with schools or similar local community stakeholders to increase attendance. Findings from this pilot study can inform future community-based adolescent substance use prevention efforts state-wide.

The engineering design process is much like the classic scientific method, where scientists ask research questions, develop hypotheses, test their hypotheses in experiments, and evaluate the results. [...]specific encouragement of girls' engineering play may build early interest and confidence in STEM-related activities. [...]new research has found that preschoolers who engage in more engineering play perform better on assessments of mathematical knowledge (numeracy, geometry), spatial ability (mentally rotating and transforming shapes), and planning skills (tracing an accurate path over patterns on a page) (Gold 2017; Gold et al. 2020). Developed with Kodo Kids and Purdue University Cooperative Extension, the videos feature early childhood educators engaged in engineering play with groups of preschoolers, along with tips for facilitating children's learning. and using it in their classrooms to facilitate play with blocks and loose parts, several teachers reported on the changes they observed:

Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β is facilitated by prior phosphorylation by ERK2 and leads to its down-regulation. In contrast, behaviorally effective chronic mood stabilizer treatments in mice inhibit GSK3β and increase FXR1P levels. In line with this, overexpression of FXR1P in the mouse prefrontal cortex also leads to comparable mood-related responses. Furthermore, functional genetic polymorphisms affecting either FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations uncovered a GSK3β/FXR1P signaling pathway that contributes to regulating mood and emotion processing. Regulation of FXR1P by GSK3β also provides a mechanistic framework that may explain how inhibition of GSK3β can contribute to the regulation of mood by psychoactive drugs in mental illnesses such as bipolar disorder. Moreover, this pathway could potentially be implicated in other biological functions, such as inflammation and cell proliferation, in which FXR1P and GSK3 are known to play a role.

ABSTRACT INTRODUCTION The information provided by pharmaceutical sales representatives has been shown to influence prescribing. To enable safe prescribing, medicines information must include harm as well as benefits. Regulation supports this aim, but relative effectiveness of different approaches is not known. The United States (US) and France directly regulate drug promotion; Canada relies on industry self-regulation. France has the strictest information standards. METHODS This is a prospective cohort study in Montreal, Vancouver, Sacramento and Toulouse. We recruited random samples of primary care physicians from May 2009 to June 2010 to report on consecutive sales visits. The primary outcome measure was “minimally adequate safety information” (mention of at least one indication, serious adverse event, common adverse event, and contraindication, and no unqualified safety claims or unapproved indications). RESULTS Two hundred and fifty-five physicians reported on 1,692 drug-specific promotions. “Minimally adequate safety information” did not differ: 1.7 % of promotions; range 0.9–3.0 % per site. Sales representatives provided some vs. no information on harm more often in Toulouse than in Montreal and Vancouver: 61 % vs. 34 %, OR = 4.0; 95 % CI 2.8–5.6, or Sacramento (39 %), OR = 2.4; 95 % CI 1.7–3.6. Serious adverse events were rarely mentioned (5–6 % of promotions in all four sites), although 45 % of promotions were for drugs with US Food and Drug Administration (FDA) “black box” warnings of serious risks. Nevertheless, physicians judged the quality of scientific information to be good or excellent in 901 (54 %) of promotions, and indicated readiness to prescribe 64 % of the time. DISCUSSION “Minimally adequate safety information” did not differ in the US and Canadian sites, despite regulatory differences. In Toulouse, consistent with stricter standards, more harm information was provided. However, in all sites, physicians were rarely informed about serious adverse events, raising questions about whether current approaches to regulation of sales representatives adequately protect patient health.

Children with major trauma have better outcomes when treated in pediatric trauma centres, but population-based data on access to these centres in Canada are lacking. We aimed to estimate the proportion of children with major trauma who accessed a pediatric trauma centre in Canada (through direct transport or transfer) and compare access across provinces. We conducted a population-based cohort study of children (aged < 16 yr) who were admitted to hospital after a major trauma (Injury Severity Score > 12) in 9 Canadian provinces (excluding Quebec) from 2016 to 2021. We estimated the adjusted incidence of access to a pediatric trauma centre across provinces using robust Poisson regression and examined the effect of age and injury severity in subgroup analyses. Of 3007 children with major trauma, 2335 (77.6%) were directly transported (n = 879, 29.2%) or transferred (n = 1456, 48.4%) to a pediatric trauma centre. Crude access to pediatric trauma centres was higher for younger children (80.9% among those aged 0 to 5 yr, 81.7% among those aged 6 to 12 yr, 69.9% among those aged 13 to 15 yr) and those with critical injuries (88.8%). Adjusted pediatric trauma centre access was lower in British Columbia (relative risk [RR] 0.68, 95% confidence interval [CI] 0.63 to 0.74), the Atlantic provinces (RR 0.80, 95% CI 0.73 to 0.88), and Saskatchewan (RR 0.77, 95% CI 0.69 to 0.86) than Ontario, but was higher in Alberta (RR 1.06, 95% CI 1.02 to 1.10) and Manitoba (RR 1.14, 95% CI 1.09 to 1.19). Interprovincial differences were present across all subgroups (p < 0.0001). Across 9 Canadian provinces, 1 in 4 children with major trauma did not receive care in a pediatric trauma centre. These results suggest the opportunity for improvement in Canadian trauma systems to ensure that all children receive optimal injury care.

Genome-Wide Association Studies (GWASs) have identified several genes associated with Schizophrenia (SCZ) and exponentially increased knowledge on the genetic basis of the disease. In addition, products of GWAS genes interact with neuronal factors coded by genes lacking association, such that this interaction may confer risk for specific phenotypes of this brain disorder. In this regard, fragile X mental retardation syndrome-related 1 (FXR1) gene has been GWAS associated with SCZ. FXR1 protein is regulated by glycogen synthase kinase-3β (GSK3β), which has been implicated in pathophysiology of SCZ and response to antipsychotics (APs). rs496250 and rs12630592, two eQTLs (Expression Quantitative Trait Loci) of FXR1 and GSK3β, respectively, interact on emotion stability and amygdala/prefrontal cortex activity during emotion processing. These two phenotypes are associated with Negative Symptoms (NSs) of SCZ suggesting that the interaction between these SNPs may also affect NS severity and responsiveness to medication. To test this hypothesis, in two independent samples of patients with SCZ, we investigated rs496250 by rs12630592 interaction on NS severity and response to APs. We also tested a putative link between APs administration and FXR1 expression, as already reported for GSK3β expression. We found that rs496250 and rs12630592 interact on NS severity. We also found evidence suggesting interaction of these polymorphisms also on response to APs. This interaction was not present when looking at positive and general psychopathology scores. Furthermore, chronic olanzapine administration led to a reduction of FXR1 expression in mouse frontal cortex. Our findings suggest that, like GSK3β, FXR1 is affected by APs while shedding new light on the role of the FXR1/GSK3β pathway for NSs of SCZ.

ObjectiveTo understand parental perspectives regarding universal newborn screening (UNS) for congenital cytomegalovirus (cCMV) in Canada.DesignA qualitative, patient-led study using the Patient and Community Engagement Research approach consisting of online focus groups and in-depth individual interviews to understand parental preferences regarding UNS for cCMV. Data were analysed iteratively using inductive thematic analysis and narrative story analysis.SettingCanada-wide study conducted via video conference from October to December 2023.Patients12 participants from five Canadian provinces who self-identified as 18 years of age or older and as having parental lived experience with cytomegalovirus (CMV) or cCMV participated in the study.ResultsWe identified three themes: (1) attitudes about UNS for cCMV, including participants’ unanimous support for UNS and confirmation that parental anxiety is not a deterrent for screening, (2) cCMV diagnosis, including the importance of coupling cCMV diagnosis with access to treatment and medical support and (3) awareness of cCMV, where participants shared their frustration about the lack of public and pregnant people’s awareness of cCMV.ConclusionsParental anxiety is not a deterrent for UNS for cCMV. Children with cCMV and their families deserve every opportunity to attain their best possible outcomes. UNS offers children with cCMV access to early intervention if they need it, and also helps to raise awareness and education to prevent future CMV infections.

In April 2021, the CDC provided supplemental funding to all 26 Prevention Research Centers (PRCs) to create the PRC Vaccine Confidence Network (VCN) to increase COVID-19 vaccine confidence and uptake in communities disparately impacted by COVID-19 and/or in vaccine hesitant populations. A key strategy to building vaccine confidence was engaging with intermediaries (i.e., mutually trusted community and practice-based organizations conducting community outreach and intervention activities) to address barriers for our shared communities of focus. These intermediaries were key in building community trust, addressing community needs and concerns, and in turn, building vaccine confidence and demand in areas and communities disproportionately affected by the pandemic. While engaging with intermediaries helped to achieve the goals of the VCN, the role of intermediaries has not been consistently and widely described in the health promotion and disease prevention literature. In this manuscript we describe three cases of VCN-PRC-intermediary collaboration in Connecticut (Yale-Griffin), Texas (University of Texas Health Houston, UTHealth Houston), and Washington (University of Washington Health Promotion Research Center, UW HPRC) during the COVID-19 pandemic as a model for vaccine intervention. We discuss the importance of intermediary collaboration in implementing community-led public health actions to increase vaccine trust and access during the COVID-19 pandemic. We describe the role of the CDC COVID-19 Response Vaccine Task Force in forming the VCN, which supported timely exchanges of information, resources, and strategies. Finally, we share lessons learned from the VCN-PRC-intermediary collaborations and how they may apply to current and future vaccine uptake and outreach.

Background The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional series of interrelated symptoms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population. Seizures are a common and extreme phenotype that can result from diverse and often elusive pathways in patients with ultrarare or undiagnosed disorders. Methods In this pilot study, we present an approach to understand the underlying pathways leading to seizures in patients from the Undiagnosed Diseases Network (UDN) by analyzing aggregated genotype and phenotype data from the UK Biobank (UKB). Specifically, we look for enriched phenotypes across UKB participants who harbor rare variants in the same gene known or suspected to be causally implicated in a UDN patient’s recessively manifesting disorder. Analyzing these milder but related associated phenotypes in UKB participants can provide insight into the disease-causing mechanisms at play in rare disease UDN patients. Results We present six vignettes of undiagnosed patients experiencing seizures as part of their recessive genetic condition. For each patient, we analyze a gene of interest: MPO , P2RX7 , SQSTM1 , COL27A1 , PIGQ , or  CACNA2D2 , and find relevant symptoms associated with UKB participants. We discuss the potential mechanisms by which the digestive, skeletal, circulatory, and immune system abnormalities found in the UKB patients may contribute to the severe presentations exhibited by UDN patients. We find that in our set of rare disease patients, seizures may result from diverse, multi-step pathways that involve multiple body systems. Conclusions Analyses of large-scale population cohorts such as the UKB can be a critical tool to further our understanding of rare diseases in general. Continued research in this area could lead to more precise diagnostics and personalized treatment strategies for patients with rare and undiagnosed conditions.