Epidemiology of drug arrests in the United States: Evidence from the national survey on drug use and health, 2015-2019.

OBJECTIVE: Following changes to drug criminalization policies, we re-examine the epidemiology of drug arrests among people who use drugs (PWUD) in the U.S. METHODS: Serial cross-sectional data from the National Survey on Drug Use and Health (2015-2019) were utilized. Past-year illicit drug use (excluding cannabis) and drug arrests were described by year, area of residence, drug use characteristics and participant demographics. Adjusted associations between race and drug arrest were estimated using multivariable logistic regression. RESULTS: Past-year illicit drug use remained consistent over time and was highest among non-Hispanic (NH) white respondents. Of those reporting past-year illicit drug use (n = 25,429), prevalence of drug arrests remained stable over time overall and in metro areas while increasing in non-metro areas. Arrests were elevated among NH Black participants and those with lower income, unemployment, housing transience, non-metro area residence, polysubstance use, history of drug injection, substance use dependence and past-year drug selling. Adjusted odds of drug arrest remained significantly higher among NH Black individuals [aOR 1.92, 95% CI 1.30, 2.84]. CONCLUSION: Despite recent shifts away from punitive drug policies, we detected no reduction in drug arrests nationally and increasing prevalence in non-metro areas. Despite reporting the lowest level of illicit substance use and drug selling, NH Black individuals had significantly increased odds of arrest across years. Findings highlight the need for further examination of policy implementation and policing practices in different settings, with more research focused non-metro areas, to address enduring structural racism in drug enforcement and its consequences for health.

Salmon Food-Specific Compounds and Their Metabolites Increase in Human Plasma and Are Associated with Cardiometabolic Health Indicators Following a Mediterranean-Style Diet Intervention.

BACKGROUND: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits. OBJECTIVES: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored. METHODS: For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with 2 servings of salmon per week for 2 5-wk periods. CHIs were assessed, and fasting plasma was collected pre- and postintervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to postintervention and associations with changes in CHIs. RESULTS: Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (false discovery rate <0.05). Increases in 2 annotated salmon FSCs and 2 metabolites were associated with improvements in CHIs, including total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. CONCLUSIONS: A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for the discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health. The trials supporting this work were registered at NCT02573129 (Mediterranean-style diet intervention) and NCT05500976 (ongoing clinical trial).

KIF16B Mediates Anterograde Transport and Modulates Lysosomal Degradation of the HIV-1 Envelope Glycoprotein.

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) is incorporated into virions at the site of particle assembly on the plasma membrane (PM). The route taken by Env to reach the site of assembly and particle incorporation remains incompletely understood. Following initial delivery to the PM through the secretory pathway, Env is rapidly endocytosed, suggesting that recycling is required for particle incorporation. Endosomes marked by the small GTPase Rab14 have been previously shown to play a role in Env trafficking. Here, we examined the role of KIF16B, the molecular motor protein that directs outward movement of Rab14-dependent cargo, in Env trafficking. Env colocalized extensively with KIF16B+ endosomes at the cellular periphery, while expression of a motor-deficient mutant of KIF16B redistributed Env to a perinuclear location. The half-life of Env labeled at the cell surface was markedly reduced in the absence of KIF16B, while a normal half-life was restored through inhibition of lysosomal degradation. In the absence of KIF16B, Env expression on the surface of cells was reduced, leading to a reduction in Env incorporation into particles and a corresponding reduction in particle infectivity. HIV-1 replication in KIF16B knockout cells was substantially reduced compared to that in wild-type cells. These results indicated that KIF16B regulates an outward sorting step involved in Env trafficking, thereby limiting lysosomal degradation and enhancing particle incorporation. IMPORTANCE The HIV-1 envelope glycoprotein is an essential component of HIV-1 particles. The cellular pathways that contribute to incorporation of envelope into particles are not fully understood. Here, we have identified KIF16B, a motor protein that directs movement from internal compartments toward the plasma membrane, as a host factor that prevents envelope degradation and enhances particle incorporation. This is the first host motor protein identified that contributes to HIV-1 envelope incorporation and replication.

Adverse Outcomes in Topical Lidocaine Exposure: A Pediatric Case Series From the United States National Poison Data System.

To examine the clinical outcomes of topical lidocaine exposures in pediatric patients reported to the National Poison Data System (NPDS). We performed a retrospective review of the NPDS in pediatric patients with topical lidocaine toxicity from 2000 to 2020. Specific data analyzed were age, exposure chronicity, medical outcome, clinical effects, treatments, and disposition. Narrative case records were requested from poison centers. Of 37 cases identified, mean age was 5 years with age distribution of 1- to 0 days (n = 8), 1 to 24 months (n = 11), and 2-18 years (n = 18). Exposure chronicity was acute in 33 (89.2%) or chronic in 4 (10.8%). Moderate effects were seen in 25 (67.6%), major effects in 10 (27%), and 2 deaths (5.4%). The most common clinical effects included cyanosis (29.7%), seizures (18.9%), central nervous systems (CNS) depression (13.5%), drowsiness/lethargy (13.5%), and tachycardia (10.8%). The most common treatments were dilution/irrigation (35.1%), intravenous (IV) fluids (29.7%), oxygen (29.7%), methylene blue (27%), benzodiazepines (13.5%), and intubation (10.8%). Non-intensive care unit (ICU) disposition occurred for 23 patients (62.2%) and ICU admission for 14 (37.8%). Case details were requested for 37 cases, 16 cases (43.2%) were provided. Of the 2 deaths, 1 had significant cardiac history. The most common use of topical lidocaine was at home prior to a dermatologic procedure (37.5%). Topical lidocaine can induce serious outcomes resulting in ICU level care or death; however, moderate/major effects were well tolerated without comorbidities. Most patients discharged home. Given frequent use of topical, especially in outpatient settings, greater vigilance should be taken with prescriptions, instructions for use, and anticipatory guidance.

Maternal nutritional status modifies heat-associated growth restriction in women with chronic malnutrition.

Rapid changes in the global climate are deepening existing health disparities from resource scarcity and malnutrition. Rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings. However, studies explicitly examining interactions between these two important environmental factors are lacking. We leveraged maternal and neonatal anthropometry data from a randomized controlled trial focused on improving preconception maternal nutrition (Women First Preconception Nutrition trial) conducted in Thatta, Pakistan, where both nutritional deficits and heat stress are prevalent. Multiple linear regression of ambient temperature and neonatal anthropometry at birth (n = 459) showed a negative association between daily maximal temperatures in the first trimester and Z-scores of birth length and head circumference. Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins, and mTORC1 signaling components in term placenta exposed to excessive heat in the first trimester. Targeted metabolomic analysis indicated ambient temperature associated alterations in maternal circulation with decreases in choline concentrations. Notably, negative impacts of heat on birth length were in part mitigated in women randomized to comprehensive maternal nutritional supplementation before pregnancy suggesting potential interactions between heat stress and nutritional status of the mother. Collectively, the findings bridge critical gaps in our current understanding of how maternal nutrition may provide resilience against adverse effects of heat stress in pregnancy.

Longitudinal Reduction in Diversity of Maternal Gut Microbiota During Pregnancy Is Observed in Multiple Low-Resource Settings: Results From the Women First Trial.

Objective: To characterize the changes in gut microbiota during pregnancy and determine the effects of nutritional intervention on gut microbiota in women from sub-Saharan Africa (the Democratic Republic of the Congo, DRC), South Asia (India and Pakistan), and Central America (Guatemala). Methods: Pregnant women in the Women First (WF) Preconception Maternal Nutrition Trial were included in this analysis. Participants were randomized to receive a lipid-based micronutrient supplement either ≥3 months before pregnancy (Arm 1); started the same intervention late in the first trimester (Arm 2); or received no nutrition supplements besides those self-administered or prescribed through local health services (Arm 3). Stool and blood samples were collected during the first and third trimesters. Findings presented here include fecal 16S rRNA gene-based profiling and systemic and intestinal inflammatory biomarkers, including alpha (1)-acid glycoprotein (AGP), C-reactive protein (CRP), fecal myeloperoxidase (MPO), and calprotectin. Results: Stool samples were collected from 640 women (DRC, n = 157; India, n = 102; Guatemala, n = 276; and Pakistan, n = 105). Gut microbial community structure did not differ by intervention arm but changed significantly during pregnancy. Richness, a measure of alpha-diversity, decreased over pregnancy. Community composition (beta-diversity) also showed a significant change from first to third trimester in all four sites. Of the top 10 most abundant genera, unclassified Lachnospiraceae significantly decreased in Guatemala and unclassified Ruminococcaceae significantly decreased in Guatemala and DRC. The change in the overall community structure at the genus level was associated with a decrease in the abundances of certain genera with low heterogeneity among the four sites. Intervention arms were not significantly associated with inflammatory biomarkers at 12 or 34 weeks. AGP significantly decreased from 12 to 34 weeks of pregnancy, whereas CRP, MPO, and calprotectin did not significantly change over time. None of these biomarkers were significantly associated with the gut microbiota diversity. Conclusion: The longitudinal reduction of individual genera (both commensals and potential pathogens) and alpha-diversity among all sites were consistent and suggested that the effect of pregnancy on the maternal microbiota overrides other influencing factors, such as nutrition intervention, geographical location, diet, race, and other demographical variables.

Accessible analysis of longitudinal data with linear mixed effects models.

Longitudinal studies are commonly used to examine possible causal factors associated with human health and disease. However, the statistical models, such as two-way ANOVA, often applied in these studies do not appropriately model the experimental design, resulting in biased and imprecise results. Here, we describe the linear mixed effects (LME) model and how to use it for longitudinal studies. We re-analyze a dataset published by Blanton et al. in 2016 that modeled growth trajectories in mice after microbiome implantation from nourished or malnourished children. We compare the fit and stability of different parameterizations of ANOVA and LME models; most models found that the nourished versus malnourished growth trajectories differed significantly. We show through simulation that the results from the two-way ANOVA and LME models are not always consistent. Incorrectly modeling correlated data can result in increased rates of false positives or false negatives, supporting the need to model correlated data correctly. We provide an interactive Shiny App to enable accessible and appropriate analysis of longitudinal data using LME models.

Advances in HIV-1 Assembly.

The assembly of HIV-1 particles is a concerted and dynamic process that takes place on the plasma membrane of infected cells. An abundance of recent discoveries has advanced our understanding of the complex sequence of events leading to HIV-1 particle assembly, budding, and release. Structural studies have illuminated key features of assembly and maturation, including the dramatic structural transition that occurs between the immature Gag lattice and the formation of the mature viral capsid core. The critical role of inositol hexakisphosphate (IP6) in the assembly of both the immature and mature Gag lattice has been elucidated. The structural basis for selective packaging of genomic RNA into virions has been revealed. This review will provide an overview of the HIV-1 assembly process, with a focus on recent advances in the field, and will point out areas where questions remain that can benefit from future investigation.

Reducing Admission for Anaphylaxis in a Pediatric Emergency Department Using a Clinical Decision Support Tool.

Introduction: Anaphylaxis is a life-threatening condition necessitating emergent management. However, the benefits of prolonged observation and indications for hospitalization are not well established. Through the implementation of a disposition-focused clinical decision support tool (CDST), this quality improvement initiative aimed to reduce hospitalization for low-risk patients presenting to the pediatric emergency department (PED) with anaphylaxis from 49% to ≤12% within 12 months of implementation. Methods: The intervention included patients 18 years and younger of age presenting with anaphylaxis to the PED. A multidisciplinary team identified a 2006 evidence-based guideline as a significant contributor to hospitalization. The updated guideline incorporated a disposition-focused CDST that stratified patients as low-risk or high-risk and recommended discharge of low-risk patients after a 4-hour observation period. The primary outcome measure was the percentage of low-risk patients hospitalized. Balancing measures included low-risk patient 72-hour return rate and PED length of stay for all comers. Secondary outcomes included a focused cost analysis. Results: Fifty-three children preintervention and 43 children postintervention presenting with anaphylaxis met low-risk criteria. Postimplementation, hospitalization of low-risk patients decreased from 49% to 7% (P < 0.0001). No low-risk patients returned in 72 hours for an anaphylaxis-related concern (P = 0.83). The median PED length of stay increased from 189 to 193 minutes (P < 0.0001). The median cost per low-risk encounter decreased by $377 (P = 0.013). Conclusions: After implementing an evidence-based disposition-focused CDST, hospitalization of low-risk patients presenting to the PED with anaphylaxis significantly decreased without an increase in 72-hour returns. In addition, patient encounters demonstrated cost savings.

Different Blood Metabolomics Profiles in Infants Consuming a Meat- or Dairy-Based Complementary Diet.

BACKGROUND: Research is limited in evaluating the mechanisms responsible for infant growth in response to different protein-rich foods; Methods: Targeted and untargeted metabolomics analysis were conducted on serum samples collected from an infant controlled-feeding trial that participants consumed a meat- vs. dairy-based complementary diet from 5 to 12 months of age, and followed up at 24 months. RESULTS: Isoleucine, valine, phenylalanine increased and threonine decreased over time among all participants; Although none of the individual essential amino acids had a significant impact on changes in growth Z scores from 5 to 12 months, principal component heavily weighted by BCAAs (leucine, isoleucine, valine) and phenylalanine had a positive association with changes in length-for-age Z score from 5 to 12 months. Concentrations of acylcarnitine-C4, acylcarnitine-C5 and acylcarnitine-C5:1 significantly increased over time with the dietary intervention, but none of the acylcarnitines were associated with infant growth Z scores. Quantitative trimethylamine N-oxide increased in the meat group from 5 to 12 months; Conclusions: Our findings suggest that increasing total protein intake by providing protein-rich complementary foods was associated with increased concentrations of certain essential amino acids and short-chain acyl-carnitines. The sources of protein-rich foods (e.g., meat vs. dairy) did not appear to differentially impact serum metabolites, and comprehensive mechanistic investigations are needed to identify other contributors or mediators of the diet-induced infant growth trajectories.

Accuracy of Parental-Reported Tetanus Vaccination Status for Children With Lacerations.

OBJECTIVES: The aim of this study was to determine whether emergency department (ED) providers are able to accurately assess whether a child with a laceration needs tetanus prophylaxis. METHODS: We conducted an 8-month prospective cross-sectional study of children presenting with a laceration to a pediatric ED. We asked ED providers whether tetanus prophylaxis was necessary. An ED pharmacist accessed the Utah Statewide Immunization Information System (USIIS), and we assessed the accuracy of the ED provider's determination of necessary tetanus prophylaxis compared with USIIS records. RESULTS: Among 375 patients aged 5 months to 17 years, ED providers made an inaccurate assessment of necessary tetanus prophylaxis in 33 cases (8.8%; 95% confidence interval [CI], 6.3%-12.1%). Emergency department providers would have inappropriately administered tetanus prophylaxis in 5 cases (1.3%; 95% CI, 0.5%-3.2%) and would have missed the need for tetanus prophylaxis in 28 cases (7.5%; 95% CI, 5.2%-10.6%). Emergency department providers were more likely to provide an inaccurate recommendation in older children (8.3 vs 4.8 years; P < 0.001), in patients with a dirty wound (45.5% vs 11.7%; P < 0.001), and in children who had fewer than 3 vaccines recorded in the USIIS (54.5% vs 1.2%; P < 0.001). CONCLUSIONS: Emergency department providers may inaccurately assess the need for tetanus prophylaxis in children. Special attention should be paid to cases of dirty wounds and cases in which fewer than 3 tetanus-containing vaccines have been given.

Notch dimerization and gene dosage are important for normal heart development, intestinal stem cell maintenance, and splenic marginal zone B-cell homeostasis during mite infestation.

Cooperative DNA binding is a key feature of transcriptional regulation. Here we examined the role of cooperativity in Notch signaling by CRISPR-mediated engineering of mice in which neither Notch1 nor Notch2 can homo- or heterodimerize, essential for cooperative binding to sequence-paired sites (SPS) located near many Notch-regulated genes. Although most known Notch-dependent phenotypes were unaffected in Notch1/2 dimer-deficient mice, a subset of tissues proved highly sensitive to loss of cooperativity. These phenotypes include heart development, compromised viability in combination with low gene dose, and the gut, developing ulcerative colitis in response to 1% dextran sulfate sodium (DSS). The most striking phenotypes-gender imbalance and splenic marginal zone B-cell lymphoma-emerged in combination with gene dose reduction or when challenged by chronic fur mite infestation. This study highlights the role of the environment in malignancy and colitis and is consistent with Notch-dependent anti-parasite immune responses being compromised in Notch dimer-deficient animals.

Longitudinal Changes of One-Carbon Metabolites and Amino Acid Concentrations during Pregnancy in the Women First Maternal Nutrition Trial.

BACKGROUND: Maternal dietary restriction and supplementation of one-carbon (1C) metabolites can impact offspring growth and DNA methylation. However, longitudinal research of 1C metabolite and amino acid (AA) concentrations over the reproductive cycle of human pregnancy is limited. OBJECTIVE: To investigate longitudinal 1C metabolite and AA concentrations prior to and during pregnancy and the effects of a small-quantity lipid-based nutrition supplement (LNS) containing >20 micronutrients and prepregnancy BMI (ppBMI). METHODS: This study was an ancillary study of the Women First Trial (NCT01883193, clinicaltrials.gov) focused on a subset of Guatemalan women (n = 134), 49% of whom entered pregnancy with a BMI ≥25 kg/m2. Ninety-five women received LNS during pregnancy (+LNS group), while the remainder did not (-LNS group). A subset of women from the Pakistan study site (n = 179) were used as a replication cohort, 124 of whom received LNS. Maternal blood was longitudinally collected on dried blood spot (DBS) cards at preconception, and at 12 and 34 wk gestation. A targeted metabolomics assay was performed on DBS samples at each time point using LC-MS/MS. Longitudinal analyses were performed using linear mixed modeling to investigate the influence of time, LNS, and ppBMI. RESULTS: Concentrations of 23 of 27 metabolites, including betaine, choline, and serine, changed from preconception across gestation after application of a Bonferroni multiple testing correction (P < 0.00185). Sixteen of those metabolites showed similar changes in the replication cohort. Asymmetric and symmetric dimethylarginine were decreased by LNS in the participants from Guatemala. Only tyrosine was statistically associated with ppBMI at both study sites. CONCLUSIONS: Time influenced most 1C metabolite and AA concentrations with a high degree of similarity between the 2 diverse study populations. These patterns were not significantly altered by LNS consumption or ppBMI. Future investigations will focus on 1C metabolite changes associated with infant outcomes, including DNA methylation. This trial was registered at clinicaltrials.gov as NCT01883193.

MRI of acquired posterior urethral diverticulum following surgery for anorectal malformations.

BACKGROUND: Posterior urethral diverticulum (PUD) is one of the most common postoperative complications associated with anorectal malformation (ARM) correction. OBJECTIVE: To describe our MRI protocol for evaluating acquired PUD following ARM surgery, and associated imaging findings. MATERIALS AND METHODS: Two radiologists retrospectively reviewed 61 pelvic MRI examinations performed for postoperative ARM for PUD identification and characteristics. Associated clinical, operative and cystoscopy reports were also reviewed and compared to MRI. RESULTS: An abnormal retrourethral focus suspicious for PUD was identified at MRI in 13 patients. Ten of these patients underwent subsequent surgery or cystoscopy, and PUD was confirmed in five. All of the confirmed PUD cases appeared as cystic lesions that were at least 1 cm in diameter in two imaging planes. Four of the false-positive cases were punctate retrourethral foci that were visible only on a single MRI plane. One patient had a seminal vesical cyst mimicking a PUD. CONCLUSION: Pelvic MRI can be a useful tool in the postoperative assessment of suspected PUD associated with ARM. Radiologists should have a high clinical suspicion for a postoperative PUD when a cystic lesion posterior to the bladder/posterior urethra is encountered on two imaging planes in these patients.