HIV Antiretroviral Treatment Adherence and Its Impact on HIV Disease Indicators in the US Military HIV Natural History Cohort Study

Background: Treatment or medication adherence is an important factor in improving HIV disease indicators among HIV-infected patients. Among members of the US Military HIV Natural History Cohort Study (NHS), we compared self-report and pharmacy-based refill adherence measures and evaluated their association to HIV disease indicators (HIV RNA viral load and CD4 counts). Methods: Self-report adherence data was retrieved for 1572 individuals from the NHS cohort during 2006-2010 while pharmacy-based refill data was collected from 2005-2009 for 1458 NHS study participants to create pharmacy-based refill adherence measures (proportion of days covered). Adherence measures and repeated measures of HIV RNA viral load and CD4 counts were analyzed using a mixed effect model to evaluate whether antiretroviral adherence impacted disease progression in this cohort. Race/ethnicity and depressive symptoms (CESD =16) were included in the final model to assess their respective mediating effects on antiretroviral adherence and HIV disease indicators. Self-report and pharmacy-based refill adherence measures were compared using Cohen’s Kappa. Chi Square test was administered to detect differences in responses between African Americans (AA) and European Americans (EA) for reasons for missed doses (barriers to treatment adherence). Results: Level of agreement in identifying optimal adherers (>=90%) was low between self-report and pharmacy-based refill measures (Cohen’s Kappa: 0.05). Using self-report adherence in the mixed effects models resulted in a decrease of 0.14 log viral load and an increase of 8.8 cells/mm3 CD4 count for every 10% increase in adherence. Pharmacy-based refill adherence was not associated with HIV RNA viral load. Race/ethnicity was an independent predictor for viral load with AA having an increase of 0.09 log viral load compared to EA keeping other covariates constant. Depressive symptoms were not significantly associated with HIV RNA viral load after adjustment. Chi square tests were significant in detecting race differences (between AA and EA) for the majority of reasons for missed doses (barriers to adherence). Conclusions: Self-reported adherence was significantly associated with HIV RNA viral load and CD4 counts. The mediating effect of race (AA) was significant in evaluating the association between treatment adherence and HIV RNA viral load. AA reported more barriers to treatment adherence in comparison to EA in this cohort.Ph.D., Epidemiology -- Drexel University, 201

Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice

Epidemiological evidence suggests that low levels of vitamin D may predispose people to develop depression and cognitive impairment. While rodent studies have demonstrated that prenatal vitamin D deficiency is associated with altered brain development, there is a lack of research examining adult vitamin D (AVD) deficiency. The aim of this study was to examine the impact of AVD deficiency on behaviour and brain function in the mouse. Ten-week old male C57BL/6J and BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We assessed a broad range of behavioural domains, excitatory and inhibitory neurotransmission in brain tissue, and, in separate groups of mice, locomotor response to d-amphetamine and MK-801. Overall, AVD deficiency resulted in hyperlocomotion in a novel open field and reduced GAD65/67 levels in brain tissue. AVD-deficient BALB/c mice had altered behaviour on the elevated plus maze, altered responses to heat, sound and shock, and decreased levels of glutamate and glutamine, and increased levels of GABA and glycine. By contrast C57BL/6J mice had a more subtle phenotype with no further behavioural changes but significant elevations in serine, homovanillic acid and 5-hydroxyindoleacetic acid. Although the behavioural phenotype of AVD did not seem to model a specific disorder, the overall reduction in GAD65/67 levels associated with AVD deficiency may be relevant to a number of neuropsychiatric conditions. This is the first study to show an association between AVD deficiency and prominent changes in behaviour and brain neurochemistry in the mouse

Potential Role of Oxidative Stress-Induced Apoptosis in Mediating Chromosomal Rearrangements in Nasopharyngeal Carcinoma

Abstract Background Genetic aberrations have been identified in nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains elusive. There are increasing evidences that the apoptotic nuclease caspase-activated deoxyribonuclease (CAD) is one of the players leading to translocation in leukemia. Oxidative stress, which has been strongly implicated in carcinogenesis, is a potent apoptotic inducer. Most of the NPC etiological factors are known to induce oxidative stress. Although apoptosis is a cell death process, cells possess the potential to survive apoptosis upon DNA repair. Eventually, the surviving cells may carry rearranged chromosomes. We hypothesized that oxidative stress-induced apoptosis may cause chromosomal breaks mediated by CAD. Upon erroneous DNA repair, cells that survive apoptosis may harbor chromosomal rearrangements contributing to NPC pathogenesis. This study focused on the AF9 gene at 9p22, a common deletion region in NPC. We aimed to propose a possible model for molecular mechanism underlying the chromosomal rearrangements in NPC. Results In the present study, we showed that hydrogen peroxide (H2O2) induced apoptosis in NPC (HK1) and normal nasopharyngeal epithelial (NP69) cells, as evaluated by flow cytometric analyses. Activity of caspases 3/7 was detected in H2O2-treated cells. This activity was inhibited by caspase inhibitor (CI). By nested Inverse Polymerase Chain Reaction (IPCR), we demonstrated that oxidative stress-induced apoptosis in HK1 and NP69 cells resulted in cleavages within the breakpoint cluster region (BCR) of the AF9 gene. The gene cleavage frequency detected in the H2O2-treated cells was found to be significantly higher than untreated control. We further found that treatment with CI, which indirectly inhibits CAD, significantly reduced the chromosomal breaks in H2O2-cotreated cells. Intriguingly, a few breakpoints were mapped within the AF9 region that was previously reported to translocate with the mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemia (ALL) patient. Conclusions In conclusion, our findings suggested that oxidative stress-induced apoptosis could be one of the mechanisms underlying the chromosomal rearrangements in NPC. CAD may play an important role in chromosomal cleavages mediated by oxidative stress-induced apoptosis. A potential model for oxidative stress-induced apoptosis mediating chromosomal rearrangements in NPC is proposed

Preliminary findings of down-regulated genes in nasopharyngeal carcinoma

The cause and mechanism of nasopharyngeal carcinoma (NPC) progression are multifactorial and multigenic in nature. Despite the increasing number of genes found to be linked with NPC, the comprehensive list of associated genetic factors remains incomplete and the precise molecular pathways to this cancer are largely undefined. Here we show early evidence of possible association between several genes and the tumourigenesis of NPC. By employing the GeneFishingTM DEG Technique that allows the comparative analysis of expression profiles between normal and tumour nasopharyngeal biopsy tissues, we have identified 10 differentially expressed genes. These genes were down-regulated in tumours relative to normal control and have never been brought into the context of NPC tumourigenicity. Our findings represent preliminary yet novel clues of several associative genetic factors to neoplastic malignancy of the nasopharynx

Expression Trend of Selected Ribosomal Protein Genes in Nasopharyngeal Carcinoma

Ribosomal proteins are traditionally associated with protein biosynthesis until recent studies that implicated their extraribosomal functions in human diseases and cancers. Our previous studies using GeneFishingTM DEG method and microarray revealed underexpression of three ribosomal protein genes, RPS26, RPS27, and RPL32 in cancer of the nasopharynx. Herein, we investigated the expression pattern and nucleotide sequence integrity of these genes in nasopharyngeal carcinoma to further delineate their involvement in tumourigenesis. The relationship of expression level with clinicopathologic factors was also statistically studied

Reflections on the Doctoral Consortium

This paper provides a reflective commentary on the British HCI Doctoral Consortium from the perspective of the Organising Committee. We discuss the approach to holding a Human Computer Interaction Doctoral Consortium in July 2020 and the outcomes. We reflect on our lived experience pre, during and post event, flagging issues and perspectives that emerged from the day, and possible implications for doctoral consortiums and training for HCI

Effect of Military Deployment on Diabetes Mellitus in Air Force Personnel

Introduction: Military deployments relocate service members to austere locations with limited medical capabilities, raising uncertainties whether members with diabetes can participate safely. Military regulations require a medical clearance for service members with diabetes prior to deployment, but there is a dearth of data that can guide the provider in this decision. To alleviate the lack of evidence in this area, we analyzed the change in glycated hemoglobin (HbA1c) and body mass index (BMI) before and after a deployment among active duty U.S. Air Force personnel who deployed with diabetes. Materials and Methods: A retrospective analysis was conducted using HbA1c and BMI values obtained within 3 mo before and within 3 mo after repatriation from a deployment of at least 90 d between January 1, 2004 through December 31, 2014. The study population consisted of 103 and 195 subjects who had an available pre- and post-deployment HbA1c and BMI values, respectively. Paired t-tests were conducted to determine significant differences in HbA1C and BMI values. Results: The majority (73.8%) of members had a HbA1c7%. BMI declined for the overall population (28.3 kg/m2 vs. 27.7 kg/m2, p \u3c 0.0001) and for most of the subgroups. Conclusion: Air Force service members who deployed with diabetes, including those with a HbA1c \u3e 7%, experienced a statistically significant improvement in HbA1c and BMI upon repatriation. A prospective study design in the future can better reconcile the effect of a military deployment on a more comprehensive array of diabetes parameters

Fibroblast and Lymphoblast Gene Expression Profiles in Schizophrenia: Are Non-Neural Cells Informative?

Lymphoblastoid cell lines (LCLs) and fibroblasts provide conveniently derived non-neuronal samples in which to investigate the aetiology of schizophrenia (SZ) using gene expression profiling. This assumes that heritable mechanisms associated with risk of SZ have systemic effects and result in changes to gene expression in all tissues. The broad aim of this and other similar studies is that comparison of the transcriptomes of non-neuronal tissues from SZ patients and healthy controls may identify gene/pathway dysregulation underpinning the neurobiological defects associated with SZ. Using microarrays consisting of 18,664 probes we compared gene expression profiles of LCLs from SZ cases and healthy controls. To identify robust associations with SZ that were not patient or tissue specific, we also examined fibroblasts from an independent series of SZ cases and controls using the same microarrays. In both tissue types ANOVA analysis returned approximately the number of differentially expressed genes expected by chance. No genes were significantly differentially expressed in either tissue when corrected for multiple testing. Even using relaxed parameters (p≤0.05, without multiple testing correction) there were still no differentially expressed genes that also displayed ≥2-fold change between the groups of SZ cases and controls common to both LCLs and fibroblasts. We conclude that despite encouraging data from previous microarray studies assessing non-neural tissues, the lack of a convergent set of differentially expressed genes associated with SZ using fibroblasts and LCLs indicates the utility of non-neuronal tissues for detection of gene expression differences and/or pathways associated with SZ remains to be demonstrated