Publications

Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients ( = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R-package. Liquid chromatography-tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC Gene expression analysis showed augmented abundance of and , as well as down-regulated expression of (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR-34a and its targets and Survival analysis based on a subset of genes from our list EMT-related genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT-affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions.

OBJECTIVE

Among African Americans, the apolipoprotein L1 () risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease.

APPROACH AND RESULTS

In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, high-risk variants were associated with increased cardiovascular mortality.

CONCLUSIONS

Among African Americans with hypertension-attributed chronic kidney disease, risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.

OBJECTIVE

Obstructive sleep apnea (OSA) remains a prevalent condition, but its occupational burden is unclear. We carried out a systematic review to characterize the consistency and magnitude of occupational associations with OSA.

METHODS

We studied OSA within three occupational categories: commercial drivers, organic solvent-exposed workers, other selected occupations. We performed a meta-analysis on the prevalence of OSA among drivers and the risk of OSA associated with solvent exposure.

RESULTS

The pooled OSA prevalence in drivers was 41% (95% confidence interval [CI] 26% to 56%) for apnea hypopnea-index (AHI) is greater than 5, and 15% (95% CI 12% to 19%) for AHI is greater than 15. Exposure to solvents was associated with increased but non-statistically significant risk of OSA: summary relative risk, 2.38 (95% CI 0.89 to 6.32). Evidence of occupational association was inconsistent for other factors.

CONCLUSIONS

OSA is common among commercial drivers and potentially associated with occupations involving likely solvent exposure.

Little is known about associations between viral suppression, adherence, and duration of prior viral suppression in sub-Saharan Africa. Study participants were from the UARTO study in Mbarara, Uganda. We fit regression models to characterize relationships between average adherence, treatment interruptions, and rebound viremia (>400 copies/mL) following a previously undetectable result. Our goal was to understand the impact of prior viral suppression on these relationships. 396 participants contributed 2864 quarterly visits. Restricted to periods with average adherence <50 %, each 10 % increase in adherence reduced the odds of rebound viremia by 74 % [adjusted odds ratio (AOR) = 0.26, P = 0.002] and 29 % (AOR = 0.71, P = 0.057) during the first 12 months of suppression and beyond 12 months respectively, interaction term P = 0.018. Among periods with adherence ≥50 %, the risk of rebound viremia decreased with increasing adherence during the first 12 months of viral suppression (AOR = 0.73 for each 10 % increase, P = 0.001), but not thereafter (AOR = 1.09, P = 0.67), interaction term P = 0.027. In contrast, 72-h interruptions, were associated with increased rebound viremia during the first 12 months (AOR = 1.30, P = 0.009) and after (AOR = 1.39, P = 0.005), interaction term P = 0.69. Completing 12 months of viral suppression decreases the impact of average adherence, but not prolonged treatment interruptions, on risk of rebound viremia.

Identifying a relationship between depression and sexual risk behavior in HIV-infected patients could establish a mechanism to enhance prevention efforts. We conducted a cross-sectional analysis using data from the University of Pennsylvania Center for AIDS Research and used ordinal logistic regression to measure the association between depression and non-condom use. 716 men who have sex with men (MSM), 262 heterosexual men and 277 heterosexual women were included. The association between depression and non-condom use was strongest in heterosexual men with and without HIV-infected regular partners (OR 8.53, 95% CI 1.18-61.89 and OR 2.30, 95% CI 0.99-5.36 respectively), but absent in heterosexual women regardless of partner. Although the OR was low in MSM overall, an association was detected in MSM without HIV-infected regular partners (OR 2.44, 95% CI 1.39-4.31). In conclusion, we demonstrated an association between depression and non-condom use driven by heterosexual men and MSM without HIV-infected regular partners. Sexual risk should be addressed when intervening on depressive symptoms in these subgroups.