Recommendations From People Who Use Drugs in Philadelphia, PA About Structuring Point-Of-Care Drug Checking

Background Adulterants, such as fentanyl and xylazine, among others, are present in a high percentage of the illicit drug supply, increasing the risk for overdose and other adverse health events among people who use drugs (PWUD). Point-of-care drug checking identifes components of a drug sample and delivers results consumers. To successfully meet the diverse needs of PWUD, more information is needed about the utility of drug checking, motivations for using services contextualized in broader comments on the drug supply, hypothesized actions to be taken after receiving drug checking results, and the ideal structure of a program. Methods In December 2021, semi-structured interviews were conducted with 40 PWUD who were accessing harm reduction services in Philadelphia, PA. Participants were asked about opinions and preferences for a future drug checking program. Interviews were audio recorded, transcribed and coded using content analysis to identify themes. Results Participants were primarily White (52.5%) and male (60%). Heroin/fentanyl was the most frequently reported drug used (72.5%, n=29), followed by crack cocaine (60.0%, n=24) and powder cocaine (47.5%, n=19). Emerging themes from potential drug checking consumers included universal interest in using a drug checking program, intentions to change drug use actions based on drug checking results, deep concern about the unpredictability of the drug supply, engaging in multiple harm reduction practices, and concerns about privacy while accessing a service. Conclusions We offer recommendations for sites considering point-of-care drug checking regarding staffing, safety, logistics, and cultural competency. Programs should leverage pre-existing relationships with organizations serving PWUD and hire people with lived experiences of drug use. They should work with local or state government to issue protections to people accessing drug checking programs and ensure the service is anonymous and that data collection is minimized to keep the program low-threshold. Programs will ideally operate in multiple locations and span “atmosphere” (e.g., from clinical to a drop-in culture), ofer in-depth education to participants about results, engage with a community advisory board, and not partner with law enforcement

Sorting Through Life: Evaluating Patient-Important Measures of Success in a Medication for Opioid Use Disorder (MOUD) Treatment Program

Background: Medication for opioid use disorder (MOUD) is the gold standard treatment for opioid use disorder. Traditionally, success in MOUD treatment is measured in terms of program retention, adherence to MOUD, and abstinence from opioid and other drug use. While clinically meaningful, these metrics may overlook other aspects of the lives of people with opioid use disorder (OUD) and surprisingly do not reflect the diagnostic criteria for OUD. Methods: Authors identified items for a pilesorting task to identify participant-driven measures of MOUD treatment success through semi-structured interviews. Interviews were transcribed verbatim and coded in Nvivo using directed and conventional content analysis to identify measures related to treatment success and quality of life goals. Participants of a low-threshold MOUD program were recruited and asked to rank identified measures in order of importance to their own lives. Multidimensional scaling (MDS) compared the similarity of items while non-metric MDS in R specified a two-dimensional solution. Descriptive statistics of participant demographics were generated in SPSS. Results: Sixteen semi-structured interviews were conducted between June and August 2020 in Philadelphia, PA, USA, and 23 measures were identified for a pilesorting activity. These were combined with 6 traditional measures for a total list of 29 items. Data from 28 people were included in pilesorting analysis. Participants identified a combination of traditional and stakeholder-defined recovery goals as highly important, however, we identified discrepancies between the most frequent and highest ranked items within the importance categories. Measures of success for participants in MOUD programs were complex, multi-dimensional, and varied by the individual. However, some key domains such as emotional well-being, decreased drug use, and attendance to basic functioning may have universal importance. The following clusters of importance were identified: emotional well-being, decreased drug use, and human functioning. Conclusions: Outcomes from this research have practical applications for those working to provide services in MOUD programs. Programs can use aspects of these domains to both provide patient-centered care and to evaluate success. Specifics from the pilesorting results may also inform approaches to collaborative goal setting during treatment

A Qualitative Exploration of the Functional, Social, and Emotional Impacts of the COVID-19 Pandemic on People Who Use Drugs

Since 2020, people who use drugs (PWUD) experienced heightened risks related to drug supply disruptions, contamination, overdose, social isolation, and increased stress. This study explored how the lives of PWUD changed in Philadelphia over a one-year period. Using semi-structured interviews with 20 participants in a Housing First, low-barrier medication for opioid use (MOUD) program in Philadelphia, the effects of the first year of the COVID-19 pandemic on the daily lives, resources, functioning, substance use, and treatment of PWUD were explored. Interviews were analyzed using a combination of directed and conventional content analysis. Six overarching themes emerged during data analysis: (1) response to the pandemic; (2) access to MOUD and support services; (3) substance use; (4) impacts on mental health, physical health, and daily functioning; (5) social network impacts; and (6) fulfillment of basic needs. Participants reported disruptions in every domain of life, challenges meeting their basic needs, and elevated risk for adverse events. MOUD service providers offset some risks and provided material supports, treatment, social interaction, and emotional support. These results highlight how there were significant disruptions to the lives of PWUD during the first year of the COVID-19 pandemic and identified critical areas for future intervention and policies

The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12

The perceived taste intensities of quinine HCl, caffeine, sucrose octaacetate (SOA) and propylthiouracil (PROP) solutions were examined in 1457 twins and their siblings. Previous heritability modeling of these bitter stimuli indicated a common genetic factor for quinine, caffeine and SOA (22–28%), as well as separate specific genetic factors for PROP (72%) and quinine (15%). To identify the genes involved, we performed a genome-wide association study with the same sample as the modeling analysis, genotyped for approximately 610 000 single-nucleotide polymorphisms (SNPs). For caffeine and SOA, no SNP association reached a genome-wide statistical criterion. For PROP, the peak association was within TAS2R38 (rs713598, A49P, P = 1.6 × 10−104), which accounted for 45.9% of the trait variance. For quinine, the peak association was centered in a region that contains bitter receptor as well as salivary protein genes and explained 5.8% of the trait variance (TAS2R19, rs10772420, R299C, P = 1.8 × 10−15). We confirmed this association in a replication sample of twins of similar ancestry (P = 0.00001). The specific genetic factor for the perceived intensity of PROP was identified as the gene previously implicated in this trait (TAS2R38). For quinine, one or more bitter receptor or salivary proline-rich protein genes on chromosome 12 have alleles which affect its perception but tight linkage among very similar genes precludes the identification of a single causal genetic variant

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Mycobacterium tuberculosis releases an antacid that remodels phagosomes

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Mining the LIPG Allelic Spectrum Reveals the Contribution of Rare and Common Regulatory Variants to HDL Cholesterol

Genome-wide association studies (GWAS) have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact. Whereas rare variant efforts have primarily focused on nonsynonymous coding variants, we hypothesized that noncoding variants in these loci are also functionally important. Using the HDL-C gene LIPG as an example, we explored the effect of regulatory variants identified through resequencing of subjects at HDL-C extremes on gene expression, protein levels, and phenotype. Resequencing a portion of the LIPG promoter and 5′ UTR in human subjects with extreme HDL-C, we identified several rare variants in individuals from both extremes. Luciferase reporter assays were used to measure the effect of these rare variants on LIPG expression. Variants conferring opposing effects on gene expression were enriched in opposite extremes of the phenotypic distribution. Minor alleles of a common regulatory haplotype and noncoding GWAS SNPs were associated with reduced plasma levels of the LIPG gene product endothelial lipase (EL), consistent with its role in HDL-C catabolism. Additionally, we found that a common nonfunctional coding variant associated with HDL-C (rs2000813) is in linkage disequilibrium with a 5′ UTR variant (rs34474737) that decreases LIPG promoter activity. We attribute the gene regulatory role of rs34474737 to the observed association of the coding variant with plasma EL levels and HDL-C. Taken together, the findings show that both rare and common noncoding regulatory variants are important contributors to the allelic spectrum in complex trait loci

A connectome and analysis of the adult Drosophila central brain.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly's brain