Neural circuit basis of adolescent THC-induced potentiation of opioid responses in adult mice.

Use of one drug of abuse typically influences the behavioral response to other drugs, either administered at the same time or a subsequent time point. The nature of the drugs being used, as well as the timing and dosing, also influence how these drugs interact. Here, we tested the effects of adolescent THC exposure on the development of morphine-induced behavioral adaptations following repeated morphine exposure during adulthood. We found that adolescent THC administration impacted morphine-induced behaviors across several dimensions, including potentiating reward and paradoxically impairing the development of morphine reward. We then mapped the whole-brain response to a reinstatement dose of morphine, finding that adolescent THC administration led to increased activity in the basal ganglia and increased functional connectivity between frontal cortical regions and the ventral tegmental area. Last, we show using rabies virus-based circuit mapping that adolescent THC exposure triggers a long-lasting elevation in connectivity from the frontal cortex regions onto ventral tegmental dopamine cells that has the potential to influence dopaminergic response to morphine administration during adulthood. Our study adds to the rich literature on the interaction between drugs of abuse and provides potential circuit substates by which adolescent THC exposure influences responses to morphine later in life.

The link between indoor air pollution from cooking fuels and anemia status among non-pregnant women of reproductive age in Ethiopia.

Objective: The effect of indoor air pollution from different fuel types on the anemia status among non-pregnant women is rarely studied. This study aimed to assess the link between indoor air pollution from different fuel types and anemia among non-pregnant women of reproductive ages in Ethiopia. Method: The secondary data from the 2016 Ethiopian Demographic and Health Survey data have been employed for this study. The anemia status of women in reproductive age was the outcome variable with multiple outcomes as (moderate to severe, mild, and no anemia) and households using biomass fuel and clean fuel were selected for this study. Multinomial logistic regression was employed to estimate the association of biomass fuel use with the anemia status controlling for the predictor variables. Relative risk ratio was calculated at 95% confidence interval. An independent-sample t-test was used to assess the mean difference in blood hemoglobin level (g/dL) between the two fuel users. A p value < 0.05 was considered significant. Result: From the total of 10,961 participants included in this study, the proportion of anemia in women of non-reproductive age was 41.8% and 19.4% among biomass fuel and clean fuel users, respectively, with a mean blood hemoglobin level of 12.71 (±1.81) g/dL. In the final model, women using biomass fuel for cooking were 47% more likely to have mild anemia than households who use cleaner fuels, whereas the association was insignificant for moderate to severe anemia. Biomass fuel users were also found to have 5.8 g/dL lower blood hemoglobin level than the clean fuel user (p < 0.001). Conclusion: The use of biomass fuel was associated with reduced blood hemoglobin levels and significantly associated with mild anemia levels in women of reproductive age in Ethiopia. National efforts should be in place to reduce indoor air pollution from biomass fuels.

Circulating plasma microRNAs in colorectal neoplasia: A pilot study in assessing response to therapy.

INTRODUCTION: Current serological surveillance markers to monitor colorectal cancer (CRC) or colorectal advanced adenomas (CAA) are hampered by poor sensitivity and specificity. The aim of this study is to identify and validate a panel of plasma microRNAs which change in expression after resection of such lesions. METHODS: A prospectively maintained colorectal surgery database was queried for patients in whom both pre- and post-procedural serum samples had been obtained. An initial screening analysis of CRC and CAA patients (5 each) was conducted using screening cards for 380 miRNAs. Four identified miRNAs were combined with a previously described panel of 7 miRNAs that were diagnostically predictive of CRC and CAA. Differential miRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR). RESULTS: Fifty patients were included (n = 27 CRC, n = 23 CAA). There was no difference in age, gender, or race profile of CRC patients compared to CAA patients. Six miRNA were significantly increased after CRC resection (miR-324, let7b, miR-454, miR-374a, miR-122, miR-19b, all p<0.05), while three miRNAs were significantly increased following CAA resection (miR-454, miR-374a, miR-122, all p<0.05). Three miRNA were increased in common for both (miR-454, miR-374a, miR-122). DISCUSSION: The expression of miRNAs associated with neoplasia (either CRC or CAA) was significantly increased following surgical resection or endoscopic removal of CRC or CAA. Future studies should focus on the evaluation of these miRNAs in CRC and CAA prognosis.

Preoperative Opioid Prescription Is Associated With Major Complications in Patients With Crohn's Disease Undergoing Elective Ileocolic Resection.

BACKGROUND: Opioid use has grown exponentially over the last decade. The effect of preoperative opioid prescription in patients with Crohn's disease undergoing surgery is unknown. OBJECTIVE: The purpose of this study was to identify whether preoperative opioid prescription is associated with adverse postoperative outcomes in Crohn's disease. DESIGN: This is a single-institution retrospective observational study. SETTINGS: This study was performed at an academic tertiary care center. Details of preoperative opioid prescription were collected from the Kentucky All-Schedule Prescription Electronic Reporting database and the electronic databases of bordering states. PATIENTS: Consecutive patients undergoing ileocolic resection for Crohn's disease from 2014 to 2018 were included. MAIN OUTCOME MEASURES: The outcomes examined were major complications (Clavien-Dindo ≥3a), length of stay, and 30-day hospital readmission. RESULTS: Fifty one of 118 patients were prescribed opioids within 6 months preoperatively (range, 0-33,760 morphine milligram equivalents). Patients with preoperative opioid prescription compared with no preoperative opioid prescription required more daily opioids during hospital admission (p = 0.024). Nineteen patients had a major postoperative complication (preoperative opioid prescription: 26% (13/51) vs no preoperative opioid prescription: 9% (6/67)). On multivariable analysis, preoperative opioid prescription (OR = 2.994 (95% CI, 1.024-8.751); p = 0.045) was a significant risk factor for a major complication. Preoperative opioid prescription was associated with increased length of stay (p < 0.001) and was a risk factor for readmission (OR = 2.978 (95% CI, 1.075-8.246); p = 0.036). Twenty-four patients were readmitted. Using a cutoff for higher opioid prescription of 300 morphine milligram equivalents within 6 months preoperation (eg, 60 tablets of hydrocodone/acetaminophen 5/325), preoperative opioid prescription remained a risk factor for major postoperative complications (OR = 3.148 (95% CI, 1.110-8.928); p = 0.031). LIMITATIONS: This was a retrospective study and could not assess nonprescribed opioid use. CONCLUSIONS: Preoperative opioid prescription was a significant risk factor for adverse outcomes in patients with Crohn's disease undergoing elective ileocolic resection. See Video Abstract at http://links.lww.com/DCR/B113. LA PRESCRIPCIÓN PREOPERATORIA DE OPIOIDES SE ASOCIA CON COMPLICACIONES MAYORES EN PACIENTES CON ENFERMEDAD DE CROHN SOMETIDOS A RESECCIÓN ILEOCÓLICA ELECTIVA: El uso de opioides ha crecido exponencialmente en la última década. Se desconoce el efecto de la prescripción preoperatoria de opioides en pacientes con enfermedad de Crohn sometidos a cirugía.Identificar si la prescripción preoperatoria de opioides está asociada con resultados postoperatorios adversos en la enfermedad de Crohn.Este es un estudio observacional retrospectivo de una sola institución.Este estudio se realizó en un centro académico de atención terciaria. Los detalles de la prescripción preoperatoria de opiáceos se recopilaron de la base de datos de "Kentucky All-Schedule Prescription Electronic Reporting" y de las bases de datos electrónicas de los estados fronterizos.Pacientes consecutivos sometidos a resección ileocólica por enfermedad de Crohn entre 2014-2018.Los resultados examinados fueron complicaciones mayores (Clavien-Dindo ≥3a), duración de la estancia y el reingreso hospitalario de 30 días.A cincuenta y uno de 118 pacientes se le recetaron opioides dentro de los 6 meses preoperatorios (rango, 0 a 33,760 equivalentes de miligramos de morfina). Los pacientes con prescripción preoperatoria de opioides en comparación con ninguna prescripción preoperatoria de opioides requirieron más opioides diarios durante el ingreso hospitalario (p = 0,024). Diecinueve pacientes tuvieron una complicación postoperatoria importante (prescripción preoperatoria de opioides: 26% [13/51] frente a ninguna prescripción preoperatoria de opioides: 9% [6/67]). En el análisis multivariable, la prescripción de opioides preoperatorios (OR = 2.994, IC 95%: 1.024-8.751, p = 0.045) fueron factores de riesgo significativos para una complicación mayor. La prescripción preoperatoria de opioides se asoció con un aumento de la duración de la estadía (p <0.001) y fue un factor de riesgo para el reingreso (OR = 2.978, IC 95%: 1.075-8.246, p = 0.036). Veinticuatro pacientes fueron readmitidos. Utilizando un límite para una mayor prescripción de opioides de 300 miligramos equivalentes de morfina dentro de los 6 meses previos a la operación (p. Ej., 60 tabletas de hidrocodona / acetaminofén 5/325), la prescripción preoperatoria de opioides siguió siendo un factor de riesgo para complicaciones postoperatorias mayores (OR = 3.148 IC 95%: 1.110-8.928, p = 0.031).Este fue un estudio retrospectivo y no pudo evaluar el uso de opioides no prescritos.La prescripción preoperatoria de opioides fue un factor de riesgo significativo para los resultados adversos en pacientes con enfermedad de Crohn sometidos a resección ileocólica electiva. Consulte Video Resumen en http://links.lww.com/DCR/B113.

The Pre-Registry Commercial Driver Medical Examination: Screening Sensitivity and Certification Lengths for Two Safety-Related Medical Conditions.

OBJECTIVE: Use independent diagnostic data to analyze the screening effectiveness of the pre-Registry commercial driver medical examination (CDME) for obstructive sleep apnea (OSA), and its sensitivity for hypertension; analyze certification lengths where relevant. METHODS: CDME screening results for 1668 drivers were compared to polysomnogram diagnostic test results, and CDME screening results were evaluated for 1155 drivers with at least one insurance claim with a hypertension diagnostic code. Any CDME documentation of the medical condition was considered as detection by screening. RESULTS: CDME sensitivity was 20.7% for moderate OSA (AHI ≥ 15). While sensitivity was 77.5% for hypertension, 93.3% of drivers with Stage 3 hypertension were certified, contrary to Federal Motor Carrier Safety Administration standards. CONCLUSIONS: The pre-Registry CDME was ineffective in screening commercial drivers for OSA. Screening was better for hypertension; incorrect certifications were given to many hypertensive drivers.

The bovine alveolar macrophage DNA methylome is resilient to infection with Mycobacterium bovis.

DNA methylation is pivotal in orchestrating gene expression patterns in various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due to Mycobacterium bovis (M. bovis) infection, has been well documented; however, the impact of this intracellular pathogen on the bAM epigenome has not been determined. Here, whole genome bisulfite sequencing (WGBS) was used to assess the effect of M. bovis infection on the bAM DNA methylome. The methylomes of bAM infected with M. bovis were compared to those of non-infected bAM 24 hours post-infection (hpi). No differences in DNA methylation (CpG or non-CpG) were observed. Analysis of DNA methylation at proximal promoter regions uncovered >250 genes harbouring intermediately methylated (IM) promoters (average methylation of 33-66%). Gene ontology analysis, focusing on genes with low, intermediate or highly methylated promoters, revealed that genes with IM promoters were enriched for immune-related GO categories; this enrichment was not observed for genes in the high or low methylation groups. Targeted analysis of genes in the IM category confirmed the WGBS observation. This study is the first in cattle examining genome-wide DNA methylation at single nucleotide resolution in an important bovine cellular host-pathogen interaction model, providing evidence for IM promoter methylation in bAM.

HomoplasyFinder: a simple tool to identify homoplasies on a phylogeny.

A homoplasy is a nucleotide identity resulting from a process other than inheritance from a common ancestor. Importantly, by distorting the ancestral relationships between nucleotide sequences, homoplasies can change the structure of the phylogeny. Homoplasies can emerge naturally, especially under high selection pressures and/or high mutation rates, or be created during the generation and processing of sequencing data. Identification of homoplasies is critical, both to understand their influence on the analyses of phylogenetic data and to allow an investigation into how they arose. Here we present HomoplasyFinder, a java application that can be used as a stand-a-lone tool or within the statistical programming environment R. Within R and Java, HomoplasyFinder is shown to be able to automatically, and quickly, identify any homoplasies present in simulated and real phylogenetic data. HomoplasyFinder can easily be incorporated into existing analysis pipelines, either within or outside of R, allowing the user to quickly identify homoplasies to inform downstream analyses and interpretation.