Rationale and design of the Kidney Precision Medicine Project

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Overcoming HIV Stigma? A Qualitative Analysis of HIV Cure Research and Stigma Among Men Who Have Sex with Men Living with HIV

Despite global progress in HIV stigma reduction, persistent HIV stigma thwarts effective HIV service delivery. Advances in HIV biomedical research toward a cure may shift perceptions of people living with HIV and HIV stigma. The purpose of this study was to examine how men who have sex with men (MSM) living with HIV in Guangzhou, China perceive HIV cure research and its potential impact on MSM and HIV stigma. We conducted in-depth interviews with 26 MSM living with HIV about their perceptions of HIV cure research and the potential impact of an HIV cure on their lives. Thematic coding was used to identify themes and structure the analysis. Two overarching themes emerged. First, participants stated that an HIV cure may have a limited impact on MSM-related stigma. Men noted that most stigma toward MSM was linked to stereotypes of promiscuity and high rates of sexual transmitted diseases in the MSM community and might persist even after a cure. Second, participants believed that an HIV cure could substantially reduce enacted, anticipated, and internalized stigma associated with HIV. These findings suggest that a biomedical cure alone would not remove the layered stigma facing MSM living with HIV. Comprehensive measures to reduce stigma are needed.     

Meta‐analysis of massively parallel reporter assays enables prediction of regulatory function across cell types

Deciphering the potential of noncoding loci to influence gene regulation has been the subject of intense research, with important implications in understanding genetic underpinnings of human diseases. Massively parallel reporter assays (MPRAs) can measure regulatory activity of thousands of DNA sequences and their variants in a single experiment. With increasing number of publically available MPRA data sets, one can now develop data‐driven models which, given a DNA sequence, predict its regulatory activity. Here, we performed a comprehensive meta‐analysis of several MPRA data sets in a variety of cellular contexts. We first applied an ensemble of methods to predict MPRA output in each context and observed that the most predictive features are consistent across data sets. We then demonstrate that predictive models trained in one cellular context can be used to predict MPRA output in another, with loss of accuracy attributed to cell‐type‐specific features. Finally, we show that our approach achieves top performance in the Fifth Critical Assessment of Genome Interpretation “Regulation Saturation” Challenge for predicting effects of single‐nucleotide variants. Overall, our analysis provides insights into how MPRA data can be leveraged to highlight functional regulatory regions throughout the genome and can guide effective design of future experiments by better prioritizing regions of interest.     

A subcostal approach is favorable compared to sternotomy for left ventricular assist device exchange field of research: artificial heart (clinical)

Journal of Artificial Organs - This is a single-center retrospective study to summarize clinical outcomes of patients requiring surgical continuous-flow left ventricular assist device (HeartMate...     

Oral malodor reduction by a palatal mucoadhesive tablet containing herbal formulation

OBJECTIVE: The aim of the present study was to test the effect of a palatal mucoadhesive tablet containing an herbal formulation on oral malodor production and volatile sulfide compound (VSC) levels, and to evaluate its antimicrobial activity. METHODS: A total of 56 healthy young volunteers participated in experiments 1 and 2. The palatal adhesive tablets were prepared with different active ingredients (herbal formulation, zinc and chlorhexidine), or without an active ingredient as control (placebo). Measurement included odor judge scores (two judges) and VSC readings by a sulfide monitor (Halimeter). In experiment 3, the antimicrobial activity of the herbal formulation ingredients (i.e. sage, Echinacea, Lavender and Mastic gum) were tested against three oral pathogens (Streptoccocus mutans, Porphyromonas gingivalis and Candida albicans) by the agar diffusion test. RESULTS: Application of the palatal adhesive tablets containing herbal formulation resulted in a significant reduction in both oral malodor scores (p<0.001) and VSC levels (p=0.013). Herbal formulation showed higher significance in VSC reduction (p=0.001), as compared to zinc and chlorhexidine (p=0.024 and 0.032, respectively). Sage, Lavender and Mastic gum showed antimicrobial activity against all three oral pathogens. CONCLUSIONS: Results of the present study suggest that the palatal adhesive tablets containing herbal formulation may serve as an effective means of treatment for patients complaining of oral malodor.     

Ultralow doses of cannabinoid drugs protect the mouse brain from inflammation‐induced cognitive damage

In our previous studies, we found that a single ultralow dose of tetrahydrocannabinol (THC; 0.002 mg/kg, three to four orders of magnitude lower than the conventional doses) protects the brain from different insults that cause cognitive deficits. Because various insults may trigger a neuroinflammatory response that leads to secondary damage to the brain, the current study tested whether this extremely low dose of THC could protect the brain from inflammation‐induced cognitive deficits. Mice received a single injection of THC (0.002 mg/kg) 48 hr before or 1–7 days after treatment with lipopolysccharide (LPS; 10 mg/kg) and were examined with the object recognition test 3 weeks later. LPS caused long‐lasting cognitive deficits, whereas the application of THC before or after LPS protected the mice from this LPS‐induced damage. The protective effect of THC was blocked by the cannabinoid (CB) 1 receptor antagonist SR14176A but not by the CB2 receptor antagonist SR141528 and was mimicked by the CB1 agonist ACEA but not by the CB2 agonist HU308. The protective effect of THC was also blocked by pretreatment with GW9662, indicating the involvement of peroxisome proliferator‐activated receptor‐γ. Biochemical examination of the brain revealed a long‐term (at least 7 weeks) elevation of the prostaglandin‐producing enzyme cyclooxygenase‐2 in the hippocampus and in the frontal cortex following the injection of LPS. Pretreatment with the extremely low dose of THC tended to attenuate this elevation. Our results suggest that an ultralow dose of THC that lacks any psychotrophic activity protects the brain from neuroinflammation‐induced cognitive damage and might be used as an effective drug for the treatment of neuroinflammatory conditions, including neurodegenerative diseases. © 2014 Wiley Periodicals, Inc.     

A motor learning-based intervention to ameliorate freezing of gait in subjects with Parkinson’s disease

Freezing of gait (FOG) is an episodic gait disturbance that is commonly seen in Parkinson’s disease (PD). To date, treatment efficacy is limited. We tested the hypothesis that an intervention that utilizes motor learning provided through intensive cueing can alleviate this symptom. Fifteen subjects with PD suffering from FOG participated in a 6 week progressive motor learning program (three training sessions per week—open trial). A training session included FOG-provoking situations (e.g., turns). Prior to each presumed FOG provocation (e.g., just before a turn), rhythmic auditory stimulation (RAS) was elicited and the subject was trained to walk rhythmically, coordinate left–right stepping and to increase step size, utilizing the RAS cueing. Net training duration increased from week to week and secondary cognitive tasks while walking were added to increase FOG propensity. FOG symptom burden was assessed before, immediately, and 4 weeks after the training period. The mean number of FOG episodes (±SEM) per 10 m of walking in a standardized gait assessment decreased from 0.52 ± 0.29 in the pre-testing to 0.15 ± 0.04 in the post-testing (p < 0.05). The duration of FOG episodes decreased from 4.3 ± 2.1 to 2.6 ± 0.6 s (p < 0.05). Additional measures (e.g., FOG questionnaire, gait speed) varied in their responsiveness to the treatment. These effects were retained 4 weeks after the training. The results of this open label study support the possibility that a motor learning-based intervention is apparently effective in reducing FOG burden, suggesting that RAS can deliver ‘anti-FOG’ training.