Explore the vast range of titles available.

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.

Millions of individuals are infected with and die from tuberculosis (TB) each year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As such, there is an urgent need to identify novel drugs to treat TB infections. Current frontline therapies include the drug isoniazid, which inhibits the essential NADH-dependent enoyl–acyl-carrier protein (ACP) reductase, InhA. To inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG. Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery of InhA inhibitors that do not require KatG activation is crucial to combat MDR TB. Multiple discovery efforts have been made against InhA in recent years. Until recently, despite achieving high potency against the enzyme, these efforts have been thwarted by lack of cellular activity. We describe here the use of DNA-encoded X-Chem (DEX) screening, combined with selection of appropriate physical properties, to identify multiple classes of InhA inhibitors with cell-based activity. The utilization of DEX screening allowed the interrogation of very large compound libraries (1011 unique small molecules) against multiple forms of the InhA enzyme in amultiplexed format. Comparison of the enriched library members across various screening conditions allowed the identification of cofactor-specific inhibitors of InhA that do not require activation by KatG, many of which had bactericidal activity in cell-based assays.

The Centers for Disease Control and Prevention (CDC)-funded Youth Violence Prevention Centers (YVPCs) apply different models to reduce youth violence that are applicable to firearm violence because they are comprehensive, cut across ecological levels, and involve multisector partners that inform firearm injury prevention strategies. In addition, all YVPCs engage youths and communities in reducing violence, which may also be a useful approach to the prevention of firearm violence. YVPCs' role in helping to address firearm violence is vital for public health because in 2019 firearms were the leading mechanism of death among youths aged 10 to 24years in the United States.1 Of the 7779 firearm-related deaths among youths in this age group in 2019, 4483 (57.6%) were attributable to homicide; 2972 (38.2%) to suicide;and 324 (4.2%) to unintentional, undetermined intent, or legal intervention.1 In addition, firearms accounted for 4483 (90.3%) of the 4965 youth homicide deaths and 2972 (45.8%) of the 6488 youth suicide deaths in 2019.1 In 2019, the youth firearm homicide rate was 7.06 per 100 000 and the youth firearm suicide rate was 4.68 per 100 000. Non-Hispanic Black youths experienced firearm homicide rates (31.02 per 100 000) that were 17.5 times higher than those of non-Hispanic White youths (1.77 per 100 000), and firearm homicides among non-Hispanic Black youths accounted for 66.2% of all youth firearm homicides in 2019.1 In total, 7455 youths aged 10 to 24years died by firearm homicide or suicide in 2019, which translates to more than 20 youths dying every day from these firearm-related injuries.1 Overall, youth firearm mortality rates in 2019 were higher in rural areas (13.25 per 100 000) than in urban areas (12.00 per 100 000). Youth firearm suicide rates were higher in rural areas than urban areas (7.64 vs 3.48 per 100 000), and youth firearm homicide rates were higher in urban areas than rural area (8.14 vs 4.84 per 100 000).2 Firearm-related mortality rates for youths have surpassed rates of motor vehicle (MV)-related deaths in the United States since 2016.1 The fact is that between 2008 and 2017, the federal government spent on average$1 million annually on research addressing firearm-related deaths among those aged 1 to 18 years, compared with $ 88 million annually on research for MV-related deaths among youths.

Statement of purposeTo determine whether risk for future violence perpetration is associated with mental and physical health problems.MethodsA community based survey exploring multiple violence characteristics was conducted prior to implementation of a Community that Cares model targeting reduction in youth violence. All youth living in high risk communities were eligible. Surveyors went door - to door to invite youth to participate. Surveyors asked questions in a confidential setting, recording answers on a computer. The Violence Injury Protection and Risk Screen (VIPRS) - predicting future violence perpetration, as well as standard violence measures - perpetration, victimisation, dating, and delinquency - were administered. Health and wellness measures - overall health, presence of chronic illness, and mental health diagnoses were collected. Chi-square analysis determined which health and wellness outcomes were associated with a positive VIPRS score. Logistic Regression determined which factors influenced the outcomes of interest. U. Colorado IRB approved the study.Results1722 youth eligible/1100 participated: 53% female, 45% Hispanic, 25% Black. 20% were VIPRS +. Youth 13-17 were more likely VIPRS + than youth 10-12: 25.8% vs. 11.0% (p = 0.000); and males > females, 27.8% vs. 13.3% (p = 0.000). There were significant associations between VIPRS + and health outcomes. VIPRS + youth had worse general health, 50% vs. 40% (p < 0.05) and were more likely to suffer from asthma, migraines, and concussions. VIPRS + youth also experienced more mental health issues (41.2% vs. 15.9%, p = 0.000) compared to VIPRS - youth. LR models showed that VIPRS + was the strongest predictor of negative health outcomes.ConclusionsScreening positive for future violence risk is strongly associated with multiple physical and mental health conditions.Significance/contributionsClinicians identifying youth at risk for future violence should consider assessing for a range of health issues; likewise, as physical and mental health issues are identified, clinicians should assess youth for violence risk.

Statement of purposeTo determine whether risk for future violence perpetration is associated with mental and physical health problems.MethodsA community based survey exploring multiple violence characteristics was conducted prior to implementation of a Community that Cares model targeting reduction in youth violence. All youth living in high risk communities were eligible. Surveyors went door – to door to invite youth to participate. Surveyors asked questions in a confidential setting, recording answers on a computer. The Violence Injury Protection and Risk Screen (VIPRS) – predicting future violence perpetration, as well as standard violence measures – perpetration, victimisation, dating, and delinquency – were administered. Health and wellness measures – overall health, presence of chronic illness, and mental health diagnoses were collected. Chi-square analysis determined which health and wellness outcomes were associated with a positive VIPRS score. Logistic Regression determined which factors influenced the outcomes of interest. U. Colorado IRB approved the study.Results1722 youth eligible/1100 participated: 53% female, 45% Hispanic, 25% Black. 20% were VIPRS +. Youth 13–17 were more likely VIPRS + than youth 10–12: 25.8% vs. 11.0% (p = 0.000);and males > females, 27.8% vs. 13.3% (p = 0.000). There were significant associations between VIPRS + and health outcomes. VIPRS + youth had worse general health, 50% vs. 40% (p < 0.05) and were more likely to suffer from asthma, migraines, and concussions. VIPRS + youth also experienced more mental health issues (41.2% vs. 15.9%, p = 0.000) compared to VIPRS – youth. LR models showed that VIPRS + was the strongest predictor of negative health outcomes.ConclusionsScreening positive for future violence risk is strongly associated with multiple physical and mental health conditions.Significance/contributionsClinicians identifying youth at risk for future violence should consider assessing for a range of health issues; likewise, as physical and mental health issues are identified, clinicians should assess youth for violence risk.

Intentional and unintentional firearm injury is the second leading cause of death for youth, underscoring the need for effective primary prevention approaches that focus on increasing safe storage by caregivers and decreasing handling/carriage among youth. This article describes the state of the science for prevention of firearm injuries among children and adolescents. We applied PRISMA guidelines to present results from a scoping review using PubMed, Scopus, CINAHL, and CJ Abstracts for original research articles published between January 1, 1985 and March 1, 2018 in the U.S. focusing on primary screening or interventions for primary prevention of pediatric firearm injuries. In total, 46 articles met inclusion criteria: safe storage (23), screening (2), firearm handling/carriage/use (21). Across school, healthcare, and community settings, few evidenced-based programs exist, and data on firearm safety technologies are lacking. Programs have generally not employed rigorous designs, and/or assessed behavioral (e.g., carriage) or injury-related firearm outcomes. Evidenced-based prevention programs are needed to mitigate firearm morbidity and mortality among youth.

BackgroundEasy firearm access increases injury risk among adolescents. We evaluated the acceptability and feasibility of improving knowledge of a 3 min safe firearm storage education video in the paediatric emergency department.MethodsWe conducted a single-centre block trial in a large paediatric emergency department (August 2020–2022). Participants were caregivers of adolescents (10–17 years) in firearm-owning households. First block participants (control) completed a baseline survey about child safety behaviours (including firearms). Second block participants (intervention) completed a baseline survey, watched the safe firearm storage video and evaluated acceptability. Participants completed a 3-month follow-up survey about firearm safety behaviours and knowledge recall. Demographic and clinical variables were compared between the intervention and control groups using Fisher’s exact and χ2 tests. McNemar’s test was used to compare firearm storage behaviours at the initial and 3-month visit within each group.ResultsResearch staff approached 1264 caregivers; 371 consented to participate (29.4%) and 144 (38.8%) endorsed firearm ownership. There were 95 participants in the control group and 62 in the intervention group. Follow-up was lower in the intervention group (53.7% vs 37.1%, p=0.04). Among participants viewing the video, 80.3% liked the video and 50.0% felt they learnt something new from the video.ConclusionsVideo-based firearm education in a paediatric emergency department is acceptable among a population of caregivers of adolescents with household firearms. This is a higher-risk group that may uniquely benefit from consistent education in the paediatric emergency department. Further study with larger populations is needed to evaluate intervention effectiveness.Trial registrationThe study was registered with ClinicalTrials.gov (NCT05168878).

BackgroundThe Gun Shop Project aims to reduce firearm suicide and is widely implemented in the USA, yet little is known about the core firearm business practices and behaviours that might contribute to preventing firearm suicide.MethodsOwners or managers of all firearm businesses identified as participants in Colorado’s Gun Shop Project were invited to respond to a questionnaire. Data collection occurred from March to May 2021. Analyses included unweighted descriptive statistics with CIs and Pearson χ2 tests for categorical associations.Results54 firearm businesses participated (response rate: 28%). Under half reported practices that are Gun Shop Project core aspects (range: 14%–45%). 22% of businesses frequently engaged customers on the importance of safe firearm storage in suicide prevention while 26% had denied a firearm sale and 14% had assisted with temporary secure storage in the past year with customers perceived to be in suicidal crisis. However, high proportions reported willingness to engage in these behaviours if a customer was in crisis: 74% were willing to refuse a sale of a firearm or ammunition, 70% were willing to discuss temporary secure storage options and 70% were willing to direct customers to mental health services.ConclusionsThis study suggests that efforts to continue educating and involving firearm businesses may have an impact on the adoption of organisational suicide prevention practices and behaviours. Ongoing efforts are needed to understand core components of Gun Shop Project to inform standardised recommendations for effective firearm business practices that prevent firearm suicide.

Firearm homicide and suicide are the leading causes of violence-related injury deaths among U.S. youth. However, evaluations of the effectiveness of firearm violence prevention programs and strategies to reducing youth firearm violence are limited. To help inform and evaluate such efforts, this study aimed to identify risk and protective factors associated with youth firearm access, possession or carrying (for reasons other than hunting or target shooting) among a sample of U.S. urban youth in the Mountain West. Findings show the influence that youth violence risk (e.g., having friends engaged in delinquency; violence; drug sales; gang fights; exposure to violence; screening positive for violence risk) can have on youth firearm access, possession or carrying. Implications for prevention and intervention are discussed.

Statement of PurposeYouth violence is a leading cause of morbidity and mortality. Adolescent primary care visits provide an opportunity for violence screening and delivery of interventions, which are not typically offered in this setting. Thus, we examined implementation of an evidenced-based behavioral intervention (SafeERteens) in primary care.Methods/ApproachAdolescents (ages 14–18) reporting past year aggression on a screening survey were eligible. A quasi-experimental deign was used, enrolling a comparison sample (e.g., resource brochure) and an intervention sample, which consisted of clinic staff delivering a 30-minute Motivational Interviewing-based brief intervention, followed by automatic text message boosters over 8 weeks. Follow-up surveys were complete at 3-months.ResultsOverall, about half (50.0%; 56.6%) of youth screened positive, with 110 enrolled (n=49 comparison; n= 61 intervention). Intervention delivery characteristics varied by clinic, including completion (75.9%; 62.5%), modality (100% telehealth; 60% telehealth/40% in-person), and enrollment in text messages (81.8%; 55.0%). In analyses comparing relative changes over time (using an intent-to-treat approach), the intervention group showed significantly greater reductions in severe peer aggression (p<0.05), anxiety (p<0.05) and substance use consequences (p<0.05) relative to the comparison group. Other outcomes examined were in the expected direction, with greater reductions in intervention vs comparison groups in peer victimization, substance use, intention to avoid fighting, and depression (all p’s<0.10). Participant and staff feedback was positive, identifying challenges to long-term implementation.ConclusionsFindings support the feasibility and preliminary effectiveness of delivering violence interventions in primary care, with key lessons learned informing future translation of behavioral interventions into routine care in primary care. Significance/Contribution to Injury and Violence PreventionPrimary care is a useful setting to identify adolescents involved with violence, and deliver interventions, which could reduce injury and improve health outcomes.