Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.     

Selective anticancer effects of a synthetic flavagline on human Oct4-expressing cancer stem-like cells via a p38 MAPK-dependent caspase-3-dependent pathway

Cancer stem cells (CSCs) are considered as the initiators of the carcinogenic process and are therefore emerging targets for innovative anticancer therapies. In order to evaluate the anticancer chemopreventive activity of flavagline derivatives, we used the pluripotent teratocarcinomal cell as a model of Oct4-expressing cancer stem-like cell and determined the underlying cellular and molecular mechanisms induced by a synthetic flavagline. We precisely investigated the effects of the flavagline derivative FL3 on the human embryonal carcinoma (EC) cell line NT2/D1 and compared the responses to those of a normal more restrictive pluripotent stem cell line (i.e. BJ fibroblast cell line). FL3 selectively inhibited the proliferation of NT2/D1 cells by inducing G₁ phase cell cycle arrest in a dose-dependent manner. Moreover, FL3 treatment specifically triggered apoptosis in association with an induction of the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and caspase-3 activation followed by a drastic downregulation of the master regulator of stemness Oct4. Forced inhibition of p38 MAPK activity by the specific pharmacological inhibitor SB203580 or by p38 MAPK gene knockdown using small-interfering RNA (siRNA) counteracted the effects of FL3, demonstrating that its chemopreventive action is related to growth inhibition and a p38-dependent caspase-3-dependent induction of apoptosis in Oct4-expressing CSCs. This study also shows that FL3 selectively kills poorly differentiated and highly aggressive carcinomal cells, but has little effect on normal stem-like cells. Thus FL3 offers great promise for cancer treatment since it is able to target the carcinogenic process without affecting normal cells.     

The effects of acute exercise on tobacco cravings and withdrawal symptoms in temporary abstinent pregnant smokers

Introduction

Smoking during pregnancy is common, and quitting at any point during pregnancy can yield benefits to both the fetus and mother. Smoking cessation is typically followed by withdrawal symptoms and a strong desire to smoke, both of which are likely to contribute to relapse. Research has shown that a bout of exercise minimizes cravings and tobacco withdrawal symptoms (TWS) after temporary abstinence in smokers, but these findings have not been replicated in pregnant smokers. This study examined the effect of 20 min of exercise on cravings (primary outcome) and TWS (secondary outcomes) among temporary abstinent, inactive pregnant smokers.

Methods

Thirty female smokers (Mean(M) age = 25.7 years, Standard Deviation(SD) = 5.5; M weeks pregnant = 18.2, SD = 5.3; Fagerstrom Test for Cigarette Dependence = 3.3, SD = 2.2; M 9.3 cigarettes/day, SD = 4.7; M hours abstained = 17.2, SD = 2.8) were randomized to 20 min of mild-to-moderate intensity exercise (EC; n = 14) or passive (PC; n = 16) condition. Cravings and TWS were assessed immediately before, during (at 10 min), immediately post, and at 10, 20, and 30 min post-condition.

Results

A 2 (condition) × 6 (time) repeated measures ANOVA revealed that the EC significantly (p < 0.05) reduced cravings (?² = 0.46) compared with the PC, across time. Non-significant, but nevertheless, large effects were evident favouring the EC over time for TWS restlessness (?² = 0.34), stress (?² = 0.24), irritability (?² = 0.21), tension (?² = 0.15), and depression (?² = 0.14).

Conclusions

Consistent with previous research, this study reveals that in pregnant smokers, a bout of exercise is associated with a reduction in cravings and similar patterns exist for TWS. Therefore, exercise may have the potential to assist in the initial stages of smoking cessation attempts during pregnancy.     

Prevalence of marijuana use at college entry and risk factors for initiation during freshman year

Background

Marijuana is currently the most commonly used drug on college campuses. Marijuana use among college students is increasing, and many students begin using marijuana during college. The goal of this study was to investigate predictors of lifetime marijuana use at college entry and initiation during freshman year.

Methods

We used responses from the first two semesters of a longitudinal study of 3146 students from 11 colleges in North Carolina and Virginia. Random-effects logistic regression models were constructed to identify factors that predict lifetime marijuana use at college entry and initiation during freshman year.

Results

Nearly 30% of students reported ever having used marijuana at college entry. Among students who had never used marijuana prior to college, 8.5% initiated use during freshman year. In multivariable logistic regression models, having at least $100 per month in spending money; attending church rarely or never; current use of cigarettes, alcohol, and hookah tobacco; lifetime use of other illicit drugs; and a higher propensity toward sensation seeking were associated with a higher likelihood of having used marijuana at least once at college entry. Hispanic ethnicity, living on campus, and current use of cigarettes and alcohol were associated with a higher likelihood of initiating marijuana use during freshman year.

Conclusion

These results have implications for targeting substance abuse prevention programs on college campuses.     

Pharmacy Students’ Ability to Identify Plagiarism After an Educational Intervention

Objective. To determine if an educational intervention in a doctor of pharmacy (PharmD) degree program increases pharmacy students’ ability to identify plagiarism.Methods. First-year (P1), second-year (P2), and third-year (P3) pharmacy students attended an education session during which types of plagiarism and methods for avoiding plagiarism were reviewed. Students completed a preintervention assessment immediately prior to the session and a postintervention assessment the following semester to measure their ability.Results. Two hundred fifty-two students completed both preintervention and postintervention assessments. There was a 4% increase from preintervention to postintervention in assessment scores for the overall student sample (p<0.05). The mean change was greatest for P1 and P2 students (5% and 4.8%, respectively).Conclusion. An educational intervention about plagiarism can significantly improve students’ ability to identify plagiarism.     

A Formal Mentorship Program for Faculty Development

Objective. To describe the development, implementation, and evaluation of a formal mentorship program at a college of pharmacy.Methods. After extensive review of the mentorship literature within the health sciences, a formal mentorship program was developed between 2006 and 2008 to support and facilitate faculty development. The voluntary program was implemented after mentors received training, and mentors and protégés were matched and received an orientation. Evaluation consisted of conducting annual surveys and focus groups with mentors and protégés.Results. Fifty-one mentor-protégé pairs were formed from 2009 to 2012. A large majority of the mentors (82.8%-96.9%) were satisfied with the mentorship program and its procedures. The majority of the protégés (≥70%) were satisfied with the mentorship program, mentor-protégé relationship, and program logistics. Both mentors and protégés reported that the protégés most needed guidance on time management, prioritization, and work-life balance. While there were no significant improvements in the proteges’ number of grant submissions, retention rates, or success in promotion/tenure, the total number of peer-reviewed publications by junior faculty members was significantly higher after program implementation (mean of 7 per year vs 21 per year, p=0.03) in the college’s pharmacy practice and administration department.Conclusions. A formal mentorship program was successful as measured by self-reported assessments of mentors and protégés.     

Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms—Workshop Report

Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.     

Insulin Resistance,Diabetes Mellitus,and Brain Structure in Bipolar Disorders

Type 2 diabetes mellitus (T2DM) damages the brain, especially the hippocampus, and frequently co-occurs with bipolar disorders (BD). Reduced hippocampal volumes are found only in some studies of BD subjects and may thus be secondary to the presence of certain clinical variables. Studying BD patients with abnormal glucose metabolism could help identify preventable risk factors for hippocampal atrophy in BD. We compared brain structure using optimized voxel-based morphometry of 1.5T MRI scans in 33 BD subjects with impaired glucose metabolism (19 with insulin resistance/glucose intolerance (IR/GI), 14 with T2DM), 15 euglycemic BD participants and 11 euglycemic, nonpsychiatric controls. The group of BD patients with IR, GI or T2DM had significantly smaller hippocampal volumes than the euglycemic BD participants (corrected p=0.02) or euglycemic, nonpsychiatric controls (corrected p=0.004). Already the BD subjects with IR/GI had smaller hippocampal volumes than euglycemic BD participants (t(32)=−3.15, p=0.004). Age was significantly more negatively associated with hippocampal volumes in BD subjects with IR/GI/T2DM than in the euglycemic BD participants (F(2, 44)=9.96, p=0.0003). The gray matter reductions in dysglycemic subjects extended to the cerebral cortex, including the insula. In conclusion, this is the first study demonstrating that T2DM or even prediabetes may be risk factors for smaller hippocampal and cortical volumes in BD. Abnormal glucose metabolism may accelerate the age-related decline in hippocampal volumes in BD. These findings raise the possibility that improving diabetes care among BD subjects and intervening already at the level of prediabetes could slow brain aging in BD.