AlleleCoder: a PERL script for coding co-dominant polymorphism data for PCA

A useful biological interpretation of diploid heterozygotes is in terms of the dose of the common allele (0, 1 or 2 copies). We have developed a PERL script that converts FASTA files into coded spreadsheets suitable for principal component analysis. In combination with R and R Commander, two- and three-dimensional plots can be generated for visualizing genetic relationships. Such plots are useful for characterizing plant genetic resources. This method nicely illustrated the spectrum of genetic diversity in tomato landraces and the varieties categorized according to human-mediated dispersa

Vasoplegic Shock treated with Methylene Blue complicated by Severe Serotonin Syndrome.

Introduction: Management of severe vasoplegic shock in overdose can be very challenging. We describe a case of severe refractory vasodilatory shock in poisoning where methylene blue (MB) was used with success. Case Report. A 70kg 15-year-old male presented 1.5 hours post ingestion of a large polypharmacy overdose of quetiapine slow release 1.5g, quetiapine immediate release 12g, desvenlafaxine slow release 5.6g, venlafaxine 1050mg, amlodipine 290mg, ramipril 100mg, fluoxetine 560mg, promethazine 500mg and an unknown amount of lithium. He developed severe vasoplegic shock that was resistant to maximal doses of noradrenaline and vasopressin. MB was administered 6.5 hour post ingestion. Within 1 hour there was an improvement in his haemodynamic status and reduction of catecholamine requirements. Twelve hours post ingestion, he developed severe serotonin syndrome that lasted 5 days as a result of interaction between MB, a reversible monoamine oxidase inhibitor, and the antidepressants taken in overdose. MB had a calculated half-life of 38 hours. Conclusion MB is a useful second or third line strategy for severe drug induced vasodilatory shock, and may be potentially life-saving. Conversely, physicians should be aware that it can interact with other drugs and cause life-threatening serotonin syndrome. Lower doses or shorter durations may be wise in patients at risk of this interaction

The Juvenile Justice Behavioral Health Services Cascade: A New Framework for Measuring Unmet Substance Use Treatment Services Needs Among Adolescent Offenders

Overview—Substance use and substance use disorders are highly prevalent among youth under juvenile justice (JJ) supervision, and related to delinquency, psychopathology, social problems, risky sex and sexually transmitted infections, and health problems. However, numerous gaps exist in the identification of behavioral health (BH) problems and in the subsequent referral, initiation and retention in treatment for youth in community justice settings. This reflects both organizational and systems factors, including coordination between justice and BH agencies. Methods and Results—This paper presents a new framework, the Juvenile Justice Behavioral Health Services Cascade (“Cascade”), for measuring unmet substance use treatment needs to illustrate how the cascade approach can be useful in understanding service delivery issues and identifying strategies to improve treatment engagement and outcomes for youth under community JJ supervision. We discuss the organizational and systems barriers for linking delinquent youth to BH services, and explain how the Cascade can help understand and address these barriers. We provide a detailed description of the sequential steps and measures of the Cascade, and then offer an example of its application from the Juvenile Justice – Translational Research on Interventions for Adolescents in the Legal System project (JJ-TRIALS), a multi-site research cooperative funded by the National Institute on Drug Abuse. Conclusion—As illustrated with substance abuse treatment, the Cascade has potential for informing and guiding efforts to improve behavioral health service linkages for adolescent offenders, developing and testing interventions and policies to improve interagency and cross-systems coordination, and informing the development of measures and interventions for improving the implementation of treatment in complex multisystem service settings

Evaluating the impact of Mexico’s drug policy reforms on people who inject drugs in Tijuana, B.C., Mexico, and San Diego, CA, United States: a binational mixed methods research agenda

Background: Policymakers and researchers seek answers to how liberalized drug policies affect people who inject drugs (PWID). In response to concerns about the failing “war on drugs,” Mexico recently implemented drug policy reforms that partially decriminalized possession of small amounts of drugs for personal use while promoting drug treatment. Recognizing important epidemiologic, policy, and socioeconomic differences between the United States—where possession of any psychoactive drugs without a prescription remains illegal—and Mexico—where possession of small quantities for personal use was partially decriminalized, we sought to assess changes over time in knowledge, attitudes, behaviors, and infectious disease profiles among PWID in the adjacent border cities of San Diego, CA, USA, and Tijuana, Baja California, Mexico. Methods: Based on extensive binational experience and collaboration, from 2012–2014 we initiated two parallel, prospective, mixed methods studies: Proyecto El Cuete IV in Tijuana (n = 785) and the STAHR II Study in San Diego (n = 575). Methods for sampling, recruitment, and data collection were designed to be compatible in both studies. All participants completed quantitative behavioral and geographic assessments and serological testing (HIV in both studies; hepatitis C virus and tuberculosis in STAHR II) at baseline and four semi-annual follow-up visits. Between follow-up assessment visits, subsets of participants completed qualitative interviews to explore contextual factors relating to study aims and other emergent phenomena. Planned analyses include descriptive and inferential statistics for quantitative data, content analysis and other mixed-methods approaches for qualitative data, and phylogenetic analysis of HIV-positive samples to understand cross-border transmission dynamics. Results: Investigators and research staff shared preliminary findings across studies to provide feedback on instruments and insights regarding local phenomena. As a result, recruitment and data collection procedures have been implemented successfully, demonstrating the importance of binational collaboration in evaluating the impact of structural-level drug policy reforms on the behaviors, health, and wellbeing of PWID across an international border. Conclusions: Our prospective, mixed methods approach allows each study to be responsive to emerging phenomena within local contexts while regular collaboration promotes sharing insights across studies. The strengths and limitations of this approach may serve as a guide for other evaluations of harm reduction policies internationally

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

The Impact of COVID-19 Vaccination on Symptoms of Anxiety and Depression before and after COVID-19 Vaccines Were Universally Available for Adults in the United States

Our objective was to examine the influence of COVID-19 vaccination on recent (i.e., past month) moderate or severe symptoms of anxiety (GAD‐7 ≥ 10) or depression (PHQ‐8 ≥10) before and after the COVID-19 vaccine became universally available for adults in the U.S. Participants belonged to the Communities, Households, and SARS-CoV-2 Epidemiology Cohort (CHASING COVID), a national longitudinal study. Our analytic population included 4,832 participants who reported vaccination status from December 2020 to December 2021 with follow-up outcomes assessed through March 2022. We emulated a hypothetical randomized experiment, a target trial, to estimate the effect of COVID-19 vaccination on symptoms of anxiety or depression. Before vaccines were universally available, participants who were vaccinated versus not had significantly lower adjusted odds of symptoms of moderate or severe anxiety (aOR: 0.79; 95% CI: 0.70-0.89). In the universal vaccine era, vaccination was associated with marginally higher adjusted odds of symptoms of moderate or severe anxiety (aOR: 1.23; 95% CI: 1.00-1.50). Vaccination did not influence subsequent moderate or severe depressive symptoms in the preuniversal vaccine era (aOR: 0.92; 95% CI: 0.82-1.03) or universal vaccine era (aOR: 1.11; 95% CI: 0.91-1.36). Research into the longitudinal relationship between COVID-19 vaccination and symptoms of depression and anxiety is warranted, with a focus on advancing understanding of potential mediators on the pathway between vaccination and mental health as well as modifiable factors, such as vaccine hesitancy or vaccine beliefs, that may help identify populations for whom vaccination may be particularly beneficial to their mental health

An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes

The proinflammatory protease caspase-1 plays pivotal roles in central pathways of innate immunity, thereby contributing to pathogen clearance. Beside its physiological role, dysregulated activity of caspase-1 is known to contribute to an increasing number of diseases. In this study, we optimized and validated a low-volume human whole blood assay facilitating the measurement of caspase-1 activation and inflammasome-related gene expression upon stimulation of the NLRP3, NLRC4 or AIM2 inflammasome. Using the NLRP3 inflammasome specific inhibitor MCC950, we were able to measure the activity of canonical or alternative NLRP3 pathways, AIM2 and NLRC4 inflammasomes in whole blood. Based on our data we assume a superposition of NLRP3 and NLRC4 inflammasome activities in human whole blood following stimulation with S. typhimurium. The optimized whole blood assay may be suitable for diagnostic and research purposes for pediatric patients who can only donate small amounts of blood

A mixed methods study to inform fatal overdose prevention in San Diego, California: perspectives from people who use drugs

Background: In the United States, community overdose education and naloxone distribution (OEND) programs have demonstrated efficacy in reducing opioid-related mortality. OEND programs have expanded across San Diego County, California, but differential naloxone accessibility among people who use drugs (PWUD) has not been assessed. We examined factors that shape individual naloxone accessibility in San Diego.Methods: We employed a convergent parallel mixed methods design using surveys (n=194) and qualitative interviews (n=20). Ordinal logistic regression examined factors associated with personal naloxone accessibility (i.e., the frequency with which participants could access naloxone within five minutes, categorized as never, sometimes, or always). Qualitative interviews explored participant perceptions of naloxone accessibility and whether and how they maintained naloxone. We organized multilevel findings into a modified social-ecological model.Results: In quantitative and qualitative samples, participants were majority male (72% and 70% respectively), non-White race/ethnicity (55% and 75%), with an average age around 42 years. In the quantitative sample, 24% never had personally accessible naloxone, 52% sometimes did, and 24% always did. Factors independently associated with greater personal naloxone accessibility were female gender (Adjusted Odds Ratio [AdjOR]: 2.51, 95% Confidence Interval [CI]: 1.31–4.85), monthly income <$500 (AdjOR: 0.42, 95%CI:0.19, 0.90), witnessing an overdose (AdjOR: 3.51, 95%CI:1.67–7.55), and knowing where to get free naloxone (AdjOR: 3.44, 95%CI: 1.79–6.75). Qualitative data suggested that naloxone was generally easy to acquire in San Diego due to community harm reduction outreach and mutual aid among peers, albeit community barriers including distance to harm reduction providers and frequent relocation/displacement for those experiencing homelessness. Individual attitudes toward overdose risk, naloxone, and community responsibility contributed to varied individual naloxone accessibility.Conclusions: This study highlights multilevel factors influencing personal naloxone accessibility among people who use drugs in San Diego, emphasizing the importance of harm reduction outreach and peer-to-peer support. We identified opportunities for interventions that address both individual attitudes and community-level barriers to improve naloxone accessibility