Isaac Lee

The gut microbiota is important for maintaining the integrity of the intestinal barrier, promoting immunological tolerance and carrying out metabolic activities that have not evolved in hosts. Intestinal dysbiosis is associated with chronic kidney disease and probiotic supplementation has been shown to be beneficial. However, it is not known whether gut microorganisms‑specifically, lactic acid bacteria (LAB) can protect against acute kidney injury (AKI). To address this issue, the present study investigated the effects of Lactobacillus salivarius BP121, an intestinal LAB isolated from the feces of newborns, in a rat model of cisplatin‑induced AKI and also in Caco‑2 human intestinal epithelial cells. BP121 prevented cisplatin‑induced AKI in rats, as demonstrated by decreases in inflammation and oxidative stress in kidney tissue and in serum levels of uremic toxins such as indoxyl sulfate (IS) and p‑cresol sulfate (PCS). BP121 also reduced intestinal permeability, as determined using fluorescein isothiocyanate‑dextran by immunohistochemical detection of tight junction (TJ) proteins such as zona occludens‑1 and occludin. The abundance of Lactobacillus spp., which are beneficial intestinal flora, was increased by BP121; this was accompanied by an increase in the concentrations of short‑chain fatty acids in feces. Additionally, H2O2‑induced TJ protein damage was reduced in Caco‑2 cells treated with BP121 culture supernatant, an effect that was reversed by the 5' AMP‑activated protein kinase (AMPK) inhibitor Compound C and Toll‑like receptor (TLR)4 inhibitor TLR4‑IN‑C34. In conclusion, this study demonstrated that L. salivarius BP121 protects against cisplatin‑induced AKI by decreasing inflammation and oxidative stress and this renoprotective effect is partially mediated by modulating the gut environment and thereby suppressing IS and PCS production as well as by regulating AMPK and TLR4 dependent TJ assembly.

Unaccustomed resistance exercise can initiate skeletal muscle remodeling and adaptive mechanisms that can confer protection from damage and enhanced strength with subsequent stimulation. The myofiber may provide the primary origin for adaptation, yet multiple mononuclear cell types within the surrounding connective tissue may also contribute. The purpose of this study was to evaluate the acute response of muscle-resident interstitial cells to contraction initiated by electrical stimulation (e-stim) and subsequently determine the contribution of pericytes to remodeling as a result of training. Mice were subjected to bilateral e-stim or sham treatment. Following a single session of e-stim, NG2 + CD45 − CD31 − (NG2 + Lin − ) pericyte, CD146 + Lin − pericyte, and PDGFRα + fibroadipogenic progenitor cell quantity and function were evaluated via multiplex flow cytometry and targeted quantitative PCR. Relative quantity was not significantly altered 24 h postcontraction, yet unique gene signatures were observed for each cell population at 3 h postcontraction. CD146 + Lin − pericytes appeared to be most responsive to contraction, and upregulation of genes related to immunomodulation and extracellular matrix remodeling was observed via RNA sequencing. Intramuscular injection of CD146 + Lin − pericytes did not significantly increase myofiber size yet enhanced ECM remodeling and angiogenesis in response to repeated bouts of e-stim for 4 wk. The results from this study provide the first evidence that CD146 + Lin − pericytes are responsive to skeletal muscle contraction and may contribute to the beneficial outcomes associated with exercise.

OBJECTIVE: This study evaluated the impact of eConsults on access to specialty care for uninsured patients in Central Texas. METHODS: eConsults for four specialties, cardiology, gastroenterology, rheumatology, and endocrinology, were implemented in a large, multi-site federally qualified health center. Data were collected on specialty care access and utilization for a one-year period before and after implementation of the new process. RESULTS: Prior to implementation, 23% of uninsured patients referred to the included specialties completed a visit with a specialist. After implementation, 62% received a specialty consultation either through an eConsult or with a face-to-face visit. Wait times for referrals improved from a median of 54 days to seven days. CONCLUSION: This project demonstrated that eConsults improve access and reduce wait times for specialty care for uninsured patients. Interventions such as this have the potential to reduce health inequalities by providing timely access to care for common specialty concerns.