Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers.

Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may play a role in the development of insulin resistance. A double-blind, placebo-controlled trial of olanzapine was performed in healthy volunteers. Twelve healthy volunteers were randomized to receive 10 mg/day of olanzapine for 7 days. Participants underwent skeletal muscle biopsies to analyze DNA methylation changes using a candidate gene approach for the insulin signaling pathway. Ninety-seven methylation sites were statistically significant (false discovery rate < 0.05 and beta difference between the groups of ≥10%). Fifty-five sites had increased methylation in the skeletal muscle of olanzapine-treated participants while 42 were decreased. The largest methylation change occurred at a site in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PPARGC1A) gene, which had 52% lower methylation in the olanzapine group. Antipsychotic treatment in healthy volunteers causes significant changes in skeletal muscle DNA methylation in the insulin signaling pathway. Future work will need to expand on these findings with expression analyses.

Comparison of brain imaging and physical health between research and clinical neuroimaging cohorts of ageing.

OBJECTIVES: To compare brain MRI measures between Adult Changes in Thought (ACT) participants who underwent research, clinical, or both MRI scans, and clinical health measures across the groups and non-MRI subjects. METHODS: Retrospective cohort study leveraging MRI, clinical, demographic, and medication data from ACT. Three neuroradiologists reviewed MRI scans using NIH Neuroimaging Common Data Elements (CDEs). Total brain and white matter hyperintensity (WMH) volumes, clinical characteristics, and outcome measures of brain and overall health were compared between groups. 1166 MRIs were included (77 research, 1043 clinical, and 46 both) and an additional 3146 participants with no MRI were compared. RESULTS: Compared to the group with research MRI only, the clinical MRI group had higher prevalence of the following: acute infarcts, chronic haematoma, subarachnoid haemorrhage, subdural haemorrhage, haemorrhagic transformation, and hydrocephalus (each P < .001). Quantitative WMH burden was significantly lower (P < .001) and total brain volume significantly higher (P < .001) in research MRI participants compared to other MRI groups. Prevalence of hypertension, self-reported cerebrovascular disease, congestive heart failure, dementia, and recent hospitalization (all P < .001) and diabetes (P = .002) differed significantly across groups, with smaller proportions in the research MRI group. CONCLUSION: In ageing populations, significant differences were observed in MRI metrics between research MRI and clinical MRI groups, and clinical health metric differences between research MRI, clinical MRI, and no-MRI groups. ADVANCES IN KNOWLEDGE: This questions whether research cohorts can adequately represent the greater ageing population undergoing imaging. These findings may also be useful to radiologists when interpreting neuroimaging of ageing.

Profiling the Skeletal Muscle Proteome in Patients on Atypical Antipsychotics and Mood Stabilizers.

Atypical antipsychotics (AAP) are used in the treatment of severe mental illness. They are associated with several metabolic side effects including insulin resistance. The skeletal muscle is the primary tissue responsible for insulin-stimulated glucose uptake. Dysfunction of protein regulation within the skeletal muscle following treatment with AAPs may play a role in the associated metabolic side effects. The objective of this study was to measure protein abundance in the skeletal muscle of patients on long-term AAP or mood stabilizer treatment. Cross-sectional muscle biopsies were obtained from patients with bipolar disorder and global protein abundance was measured using stable isotope labeling by amino acid (SILAC) combined with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Sixteen patients completed muscle biopsies and were included in the proteomic analyses. A total of 40 proteins were significantly different between the AAP group and the mood stabilizer group. In-silico pathway analysis identified significant enrichment in several pathways including glucose metabolism, cell cycle, apoptosis, and folate metabolism. Proteome abundance changes also differed based on protein biological processes and function. In summary, significant differences in proteomic profiles were identified in the skeletal muscle between patients on AAPs and mood stabilizers. Future work is needed to validate these findings in prospectively sampled populations.

Personal genotyping and student outcomes in genetic and pharmacogenetic teaching: a systematic review and meta-analysis.

Aim: Teaching of genetics and pharmacogenetics with personal genotyping (PGT) is becoming commonplace. We aimed to perform a systematic review and meta-analysis to understand the effects of PGT on student outcomes. Methods: A systematic review was performed on studies that reported the effects of PGT on student attitudes, perceptions or knowledge. Extracted data were summarized qualitatively and when possible, quantitatively. Results: Student PGT has a positive effect on student attitude and perceptions survey responses in studies without a control group (p = 0.009) and in studies with a control group (p = 0.025). Knowledge increased after the use of PGT (p < 0.001) in studies without a control group. Conclusion: The findings here suggest that perceptions, attitudes and knowledge increase with PGT in the classroom.

Bibliometric data based on the Pharm.D. and Ph.D. degree in United States research-intensive colleges of pharmacy.

OBJECTIVES: The objective of this work was to compare bibliometrics based on doctoral degrees within United States colleges of pharmacy to understand productivity differences. Secondary objectives were to provide quantitative data based on degree that could be utilized by individual faculty, administration and other key stakeholders in academic pharmacy. METHODS: Bibliometric indices were obtained from Scopus and Web of Science for faculty from research-intensive United States pharmacy schools. Scholarly metrics that included publication number, total citations, highest cited article and H-index were compared between degrees using multivariate regression adjusted for academic rank and years since first publication. A correction for multiple testing was applied. KEY FINDINGS: All collected scholarly metrics were higher for Ph.D.-only and Pharm.D./Ph.D. faculty when compared to Pharm.D.-only faculty. Ph.D.-only faculty significantly differed compared to Pharm.D./Ph.D. faculty for Web of Science average citations per document. CONCLUSIONS: Differences are apparent between the major doctoral degrees at research-intensive, federally funded colleges of pharmacy; however, these differences were primarily identified for Pharm.D.-only compared to the other doctoral degree types Future work should analyse the potential variables that explain the scholarly metrics differences between degrees and aim to analyse other areas of faculty impact beyond scholarly metrics.

Epigenetic Responses to Acute Resistance Exercise in Trained vs. Sedentary Men.

Bagley, JR, Burghardt, KJ, McManus, R, Howlett, B, Costa, PB, Coburn, JW, Arevalo, JA, Malek, MH, and Galpin, AJ. Epigenetic responses to acute resistance exercise in trained vs. sedentary men. J Strength Cond Res 34(6): 1574-1580, 2020-Acute resistance exercise (RE) alters DNA methylation, an epigenetic process that influences gene expression and regulates skeletal muscle adaptation. This aspect of cellular remodeling is poorly understood, especially in resistance-trained (RT) individuals. The study purpose was to examine DNA methylation in response to acute RE in RT and sedentary (SED) young men, specifically targeting genes responsible for metabolic, inflammatory, and hypertrophic muscle adaptations. Vastus lateralis biopsies were performed before (baseline), 30 minutes after, and 4 hours after an acute RE bout (3 × 10 repetitions at 70% 1 repetition maximum [1RM] leg press and leg extension) in 11 RT (mean ± SEM: age = 26.1 ± 1.0 years; body mass = 84.3 ± 0.2 kg; leg press 1RM = 412.6 ± 25.9 kg) and 8 SED (age = 22.9 ± 1.1 years; body mass = 75.6 ± 0.3 kg; leg press 1RM = 164.8 ± 22.5 kg) men. DNA methylation was analyzed through methylation sensitive high-resolution melting using real-time polymerase chain reaction. Separate 2 (group) × 3 (time) repeated-measures analyses of variance and analyses of covariance were performed to examine changes in DNA methylation for each target gene. Results showed that acute RE (a) hypomethylated LINE-1 (measure of global methylation) in RT but not SED, (b) hypermethylated metabolic genes (GPAM and SREBF2) in RT, while lowering SREBF2 methylation in SED, and (c) did not affect methylation of genes associated with inflammation (IL-6 and TNF-α) or hypertrophy (mTOR and AKT1). However, basal IL-6 and TNF-α were lower in SED compared with RT. These findings indicate the same RE stimulus can illicit different epigenetic responses in RT vs. SED men and provides a molecular mechanism underpinning the need for differential training stimuli based on subject training backgrounds.

A bibliometric analysis of the top 50 NIH-Funded colleges of pharmacy using two databases.

BACKGROUND: Scholarly productivity is an essential component of college of pharmacy activities and may depend on university rank, faculty type, faculty rank and department. Bibliometric measures provide a means to analyze scholarly productivity from colleges of pharmacy while accounting for these various factors. OBJECTIVES: To analyze bibliometric data from two databases based on Carnegie Research Classification and NIH-funding rank; provide descriptions of bibliometric data based on department type and faculty classification; and examine the distribution of publications in the top 50 NIH-funded Colleges of Pharmacy. METHODS: Faculty rosters were gathered for the top 50 NIH-funded colleges of pharmacy, and names were searched in Scopus and Web of Science to establish bibliometric records. Bibliometric indices were compared based on Carnegie Basic Classification and between the NIH funding ranks 1-25 versus 26-50 using WOS bibliometric data. Descriptive statistics were presented, and Pareto distributions were developed for total publications across all schools included. RESULTS: Schools in the top 25 for NIH funding and schools with a Carnegie R1 classification had significantly higher bibliometric measures compared to schools ranked 26-50 and schools classified as R2, respectively. For faculty members with a bibliometric record (i.e., at least one publication), 20% provide approximately 60% of the publications. Additionally, approximately 90% of publications are provided by 50% of faculty records. Faculty records from basic science departments, as compared to clinical pharmacy departments, represent the highest contributing groups in the Pareto analysis. CONCLUSION: Bibliometric indices are higher at colleges of pharmacy with greater NIH funding or an R1 Carnegie classification. A minority of faculty provides most publications in colleges of pharmacy, which is composed of members from basic science departments. The descriptive data provided here is useful for understanding readily available bibliometric data based on department type and faculty classification and rank.

Skeletal muscle DNA methylation modifications and psychopharmacologic treatment in bipolar disorder.

Both severe mental illness and atypical antipsychotics have been independently associated with insulin resistance and weight gain. Altered regulation of skeletal muscle DNA methylation may play a role. We aimed to evaluate DNA methylation modifications in human skeletal muscle samples to further understand its potential role in the metabolic burden observed in psychiatric patients and psychopharmacologic treatment. Subjects were included in our study if they had a bipolar diagnosis and were currently treated with a mood stabilizer or atypical antipsychotic. A healthy control group free of psychiatric or physical disease was also included for comparisons. Anthropometric, BMI and hemoglobin A1C (HbA1C%) were measured. Fasting skeletal muscle biopsies were obtained and methylation levels of 5-methycytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 5-formylcytosine (5-fC) were measured. Skeletal muscle global methylation of 5-mC and 5-fC were significantly higher in bipolar subjects compared to healthy controls. 5-mC was significantly higher in the AAP group compared to the mood stabilizer group. Significant correlations were observed between 5-fC methylation and HbA1C%. Our findings suggest that psychiatric disease and treatment may influence some methylation measures in the skeletal muscle of patients with bipolar disorder, which may be further influenced by medication treatment.

Atypical Antipsychotics and the Human Skeletal Muscle Lipidome.

Atypical antipsychotics (AAPs) are a class of medications associated with significant metabolic side effects, including insulin resistance. The aim of this study was to analyze the skeletal muscle lipidome of patients on AAPs, compared to mood stabilizers, to further understand the molecular changes underlying AAP treatment and side effects. Bipolar patients on AAPs or mood stabilizers underwent a fasting muscle biopsy and assessment of insulin sensitivity. A lipidomic analysis of total fatty acids (TFAs), phosphatidylcholines (PCs) and ceramides (CERs) was performed on the muscle biopsies, then lipid species were compared between treatment groups, and correlation analyses were performed with insulin sensitivity. TFAs and PCs were decreased and CERs were increased in the AAP group relative to those in the mood stabilizer group (FDR q-value <0.05). A larger number of TFAs and PCs were positively correlated with insulin sensitivity in the AAP group compared to those in the mood stabilizer group. In contrast, a larger number of CERs were negatively correlated with insulin sensitivity in the AAP group compared to that in the mood stabilizer group. The findings here suggest that AAPs are associated with changes in the lipid profiles of human skeletal muscle when compared to mood stabilizers and that these changes correlate with insulin sensitivity.

Changes in the relative abundance and movement of insect pollinators during the flowering cycle of Brassica rapa crops: implications for gene flow.

The potential movement of transgenes from genetically modified crops to non-genetically modified crops via insect-mediated pollen dispersal has been highlighted as one of the areas of greatest concern in regards to genetically modified crops. Pollen movement depends sensitively on spatial and temporal variation in the movement of insect pollinators between crop fields. This study tested the degree of variation in the diversity and relative abundance of flower-visiting insects entering versus leaving pak choi, Brassica rapa var. chinensis L. (Brassicales: Brassicaceae), crops throughout different stages of the flowering cycle. The relative abundance of flower-visiting insects varied significantly with Brassica crop phenology. Greater numbers of flower-visiting insects were captured inside rather than outside the crop fields, with the highest capture rates of flower-visitors coinciding with the peak of flowering in both spring-flowering and summer-flowering crops. Moreover, the ratio of flower-visiting insects entering versus leaving crop fields also varied considerably with changing crop phenology. Despite high variation in relative capture rates, the data strongly indicate non-random patterns of variation in insect movement in relation to crop phenology, with early-season aggregation of flower-visiting insects entering and remaining in the crop, and then mass emigration of flower-visiting insects leaving the crop late in the flowering season. Although pollen movement late in the flowering cycle might contribute relatively little to total seed set (and hence crop production), the findings here suggest that extensive late-season pollinator redistribution in the landscape could contribute disproportionately to long-distance gene movement between crops.