CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model.

BACKGROUND/OBJECTIVES: CYP2A6 (CYP2A5 in mice) is mainly expressed in the liver. Hepatic CYP2A6 expression is increased in patients with non-alcoholic fatty liver disease (NAFLD). In mice, hepatic CYP2A5 is induced by high fat diet (HFD) feeding. Hepatic CYP2A5 is also increased in monosodium glutamate-induced obese mice. NAFLD is associated with obesity. In this study, we examined whether obesity is related to CYP2A6. SUBJECTS/METHODS: Obesity genetic association study: The SAGE is a comprehensive genome-wide association study (GWAS) with case subjects having a lifetime history of alcohol dependence and control subjects never addicted to alcohol. We used 1030 control individuals with self-reported height and weight. A total of 12 single nucleotide polymorphisms (SNP) within the CYP2A6 gene were available. Obesity was determined as a BMI ≥30: 30-34.9 (Class I obesity) and ≥35 (Class II and III obesity). Animal experiment study: CYP2A5 knockout (cyp2a5-/-) mice and wild type (cyp2a5+/+) mice were fed HFD for 14 weeks. Body weight was measured weekly. After an overnight fast, the mice were sacrificed. Liver and blood were collected for biochemical assays. RESULTS: Single marker analysis showed that three SNPs (rs8192729, rs7256108, and rs7255443) were associated with class I obesity (p < 0.05). The most significant SNP for obesity was rs8192729 (odds ratio (OR) = 1.94, 95% confidence intervals = 1.21-3.10, p = 0.00582). After HFD feeding, body weight was increased in cyp2a5-/- mice to a greater extent than in cyp2a5+/+ mice, and fatty liver was more pronounced in cyp2a5-/- mice than in cyp2a5+/+ mice. PPARα deficiency in cyp2a5-/- mice developed more severe fatty liver, but body weight was not increased significantly. CONCLUSION: CYP2A6 is associated with human obesity; CYP2A5 protects against obesity and NAFLD in mice. PPARα contributes to the CYP2A5 protective effects on fatty liver but it opposes to the protective effects on obesity.

Characterization of Plasmodium Falciparum Resistance Genes to Common Antimalarial Drugs in Semi-urban Areas of Burkina Faso.

INTRODUCTION: Malaria still remains the most frequent parasitic disease on the world with, in 2022, 249 million cases and 608,000 deaths worldwide. Malaria control is compromised by the spread of the parasite's resistance to available antimalarials. The objective of our study is to characterize the Plasmodium falciparum resistance genes to common antimalarial drugs in semi-urban areas of Burkina Faso. MATERIALS AND METHODS: This is a prospective cross-sectional study whose collection took place from June to October 2021 and from June to October 2022 in five health facilities in Burkina Faso. The molecular analysis based on PCR-RFLP took place from January to June 2023 at Centre National de Recherche et de Formation (CNRFP) to determine resistance genes such as Pfcrt, Pfmdr1, Pfdhps, and Pfdhfr. RESULTS: A total of 150 samples were analyzed giving a prevalence of 46.67, 1.33, 0.67, 20, 82, and 4.67%, for Pfcrt 76 T, Pfmdr1 86Y, Pfdhps 437G, Pfdhfr 51I, Pfdhfr 59R, and Pfdhfr 108N mutations, respectively. There are no mutations observed Pfdhps 540E and Pfdhfr 164L positions. However, mutation on Pfdhfr 59R position was the most common. In addition, triple mutation (Pfdhps 437G + Pfdhfr 59R + Pfdhfr 108N) was found with a low frequency which is 0.67%. CONCLUSION: Surveillance of Plasmodium falciparum resistance markers to antimalarial drugs, remains one of the priorities in the context of the control or malaria elimination.

Effects of antibiotic suppression on three healthcare systems' National Healthcare Safety Network Antibiotic Resistance Option data.

Objective: The National Healthcare Safety Network (NHSN) Antibiotic Resistance (AR) Option is a valuable tool that can be used by acute-care hospitals to track and report antibiotic resistance rate data. Selective and cascading reporting results in suppressed antibiotic susceptibility results and has the potential to adversely affect what data are submitted into the NHSN AR Option. We describe the effects of antibiotic suppression on NHSN AR Option data. Methods: NHSN AR Option data were collected from 14 hospitals reporting into an existing NHSN user group from January 1, 2017, to December 31, 2018, and linked to commercial automated antimicrobial susceptibility testing instruments (cASTI) that were submitted as part of unrelated Tennessee Emerging Infections Program surveillance projects. A susceptibility result was defined as suppressed if the result was not found in the NHSN AR Option data but was reported in the cASTI data. Susceptibility results found in both data sets were described as released. Proportions of suppressed and released results were compared using the Pearson χ2 and Fisher exact tests. Results: In total, 852 matched isolates with 3,859 unique susceptibilities were available for analysis. At least 1 suppressed antibiotic susceptibility result was available for 726 (85.2%) of the isolates. Of the 3,859 susceptibility results, 1,936 (50.2%) suppressed antibiotic susceptibility results were not reported into the NHSN AR option when compared to the cASTI data. Conclusion: The effect of antibiotic suppression described in this article has significant implications for the ability of the NHSN AR Option to accurately reflect antibiotic resistance rates.

Relaxant Effects of the Aqueous Extract of Excoecaria grahamii (Euphorbiaceae) Leaves on Uterine Horn Contractility in Wistar Rats.

In uterine smooth muscle, the effects of Excoecaria grahamii are not yet documented. To fill this gap, we investigated the pharmacological effect of Excoecaria grahamii on the contraction of the rat isolated uterine horns. The isolated segments were exposed to different concentrations of the aqueous extract of Excoecaria grahamii leaves and pharmacological drugs. The results showed that Excoecaria grahamii aqueous extract decreased the amplitude and frequency by concentration-related manner. IC50 values were 2.4 and 2.6, respectively, for amplitude and frequency. Our study revealed that the extract did not act through histamine H2-receptors or the nitric oxide pathway. It also inhibited uterine contractions induced by oxytocin and potassium chloride (KCl). These data suggest that Excoecaria grahamii active compound can be used for calming uterine contractions. The action of Excoecaria grahamii showed that it can be useful to fight against diseases which caused uterotonic effects. It can be useful to prevent preterm birth and pains caused by menstruations but further investigation is needed to clarify the mechanism action.

Population-based assessment of patient and provider characteristics influencing pediatric outpatient antibiotic use in a high antibiotic-prescribing state.

OBJECTIVE: To identify patient and provider characteristics associated with high-volume antibiotic prescribing for children in Tennessee, a state with high antibiotic utilization. DESIGN: Cross-sectional, retrospective analysis of pediatric (aged <20 years) outpatient antibiotic prescriptions in Tennessee using the 2016 IQVIA Xponent (formerly QuintilesIMS) database. METHODS: Patient and provider characteristics, including county of prescription fill, rural versus urban county classification, patient age group, provider type (nurse practitioner, physician assistant, physician, or dentist), physician specialty, and physician years of practice were analyzed. RESULTS: Tennessee providers wrote 1,940,011 pediatric outpatient antibiotic prescriptions yielding an antibiotic prescribing rate of 1,165 per 1,000 population, 50% higher than the national pediatric antibiotic prescribing rate. Mean antibiotic prescribing rates varied greatly by county (range, 39-2,482 prescriptions per 1,000 population). Physicians wrote the greatest number of antibiotic prescriptions (1,043,030 prescriptions, 54%) of which 56% were written by general pediatricians. Pediatricians graduating from medical school prior to 2000 were significantly more likely than those graduating after 2000 to be high antibiotic prescribers. Overall, 360 providers (1.7% of the 21,798 total providers in this dataset) were responsible for nearly 25% of both overall and broad-spectrum antibiotic prescriptions; 20% of these providers practiced in a single county. CONCLUSIONS: Fewer than 2% of providers account for 25% of pediatric antibiotic prescriptions. High antibiotic prescribing for children in Tennessee is associated with specific patient and provider characteristics that can be used to design stewardship interventions targeted to the highest prescribing providers in specific counties and specialties.

Analysis of a high-prescribing state's 2016 outpatient antibiotic prescriptions: Implications for outpatient antimicrobial stewardship interventions.

OBJECTIVE: To identify prescriber characteristics that predict antibiotic high-prescribing behavior to inform statewide antimicrobial stewardship interventions. DESIGN: Retrospective analysis of 2016 IQVIA Xponent, formerly QuintilesIMS, outpatient retail pharmacy oral antibiotic prescriptions in Tennessee. SETTING: Statewide retail pharmacies filling outpatient antibiotic prescriptions. PARTICIPANTS: Prescribers who wrote at least 1 antibiotic prescription filled at a retail pharmacy in Tennessee in 2016. METHODS: Multivariable logistic regression, including prescriber gender, birth decade, specialty, and practice location, and patient gender and age group, to determine the association with high prescribing. RESULTS: In 2016, 7,949,816 outpatient oral antibiotic prescriptions were filled in Tennessee: 1,195 prescriptions per 1,000 total population. Moreover, 50% of Tennessee's outpatient oral antibiotic prescriptions were written by 9.3% of prescribers. Specific specialties and prescriber types were associated with high prescribing: urology (odds ratio [OR], 3.249; 95% confidence interval [CI], 3.208-3.289), nurse practitioners (OR, 2.675; 95% CI, 2.658-2.692), dermatologists (OR, 2.396; 95% CI, 2.365-2.428), physician assistants (OR, 2.382; 95% CI, 2.364-2.400), and pediatric physicians (OR, 2.340; 95% CI, 2.320-2.361). Prescribers born in the 1960s were most likely to be high prescribers (OR, 2.574; 95% CI, 2.532-2.618). Prescribers in rural areas were more likely than prescribers in all other practice locations to be high prescribers. High prescribers were more likely to prescribe broader-spectrum antibiotics (P < .001). CONCLUSIONS: Targeting high prescribers, independent of specialty, degree, practice location, age, or gender, may be the best strategy for implementing cost-conscious, effective outpatient antimicrobial stewardship interventions. More information about high prescribers, such as patient volumes, clinical scope, and specific barriers to intervention, is needed.

Variable reduction for past year alcohol and drug use in unmet need for mental health services among US adults.

BACKGROUND: No previous study has focused on the inter-relationship among alcohol and drug use variables in the past year. This study aimed to classify the past year alcohol and drug use variables and investigate the selected variables in past year alcohol and drug use with the unmet need for mental health services among US adults. METHODS: Data came from the 2015 National Survey on Drug Use and Health (NSDUH). Oblique principal component cluster analysis (OPCCA) was used to classify 37 variables on alcohol and drug use in the past year into disjoint clusters. Weighted multiple logistic regression analysis was used to examine the associations of selected variables with the unmet need. RESULTS: 37 alcohol and drug use variables were divided into 7 clusters. The variable with the lowest 1-R2 ratio (R2 is the squared correlation) from each cluster was selected as follows: tobacco use, pain reliever use, tranquilizer use, stimulant use, zolpidem products use, illicit drug and alcohol use, and benzodiazepine tranquilizers misuse. Multiple logistic regression analysis showed that pain reliever use (OR = 1.33, 95% CI = 1.17-1.50), tranquilizer use (OR = 2.49, 95% CI = 2.16-2.86), stimulant use (OR = 1.22, 95% CI = 1.01-1.47), and illicit drug and alcohol use (OR = 1.54, 95% CI = 1.34-1.77) revealed positive associations with the unmet need for mental health services. CONCLUSION: This is the first study using OPCCA to reduce the dominations of alcohol and drug use; several alcohol and drug use variables in the past year were associated with unmet need of mental health services.

Principal component analysis of early alcohol, drug and tobacco use with major depressive disorder in US adults.

Early alcohol, tobacco and drug use prior to 18 years old are comorbid and correlated. This study included 6239 adults with major depressive disorder (MDD) in the past year and 72,010 controls from the combined data of 2013 and 2014 National Survey on Drug Use and Health (NSDUH). To deal with multicollinearity existing among 17 variables related to early alcohol, tobacco and drug use prior to 18 years old, we used principal component analysis (PCA) to infer PC scores and then use weighted multiple logistic regression analyses to estimate the associations of potential factors and PC scores with MDD. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The overall prevalence of MDD was 6.7%. The first four PCs could explain 57% of the total variance. Weighted multiple logistic regression showed that PC1 (a measure of psychotherapeutic drugs and illicit drugs other than marijuana use), PC2 (a measure of cocaine and hallucinogens), PC3 (a measure of early alcohol, cigarettes, and marijuana use), and PC4 (a measure of cigar, smokeless tobacco use and illicit drugs use) revealed significant associations with MDD (OR = 1.12, 95% CI = 1.08-1.16, OR = 1.08, 95% CI = 1.04-1.12, OR = 1.13, 95% CI = 1.07-1.18, and OR = 1.15, 95% CI = 1.09-1.21, respectively). In conclusion, PCA can be used to reduce the indicators in complex survey data. Early alcohol, tobacco and drug use prior to 18 years old were found to be associated with increased odds of adult MDD.