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Roh, M.

Publications and source records attributed to Roh, M..

2 recordsLinked to original sources

The seasonality of diarrheal pathogens: A retrospective study of seven sites over three years

BackgroundPediatric diarrhea can be caused by a wide variety of pathogens, from bacteria to viruses to protozoa. Pathogen prevalence is often described as seasonal, peaking annually and associated with specific weather conditions. Although many studies have described the seasonality of diarrheal disease, these studies have occurred predominantly in temperate regions. In tropical and resource-constrained settings, where nearly all diarrhea-associated mortality occurs, the seasonality of many diarrheal pathogens has not been well characterized. As a retrospective study, we analyze the seasonal prevalence of diarrheal pathogens among children with moderate-to-severe diarrhea (MSD) over three years from the seven sites of the Global Enteric Multicenter Study (GEMS), a case-control study. Using data from this expansive study on diarrheal disease, we characterize the seasonality of different pathogens, their association with site-specific weather patterns, and consistency across study sites. Methodology/Principal FindingsUsing traditional methodologies from signal processing, we found that certain pathogens peaked at the same time every year, but not at all sites. We also found associations between pathogen prevalence and weather or "seasons", which are defined by applying modern machine-learning methodologies to site-specific weather data. In general, rotavirus was most prevalent during the drier "winter" months and out of phase with bacterial pathogens, which peaked during hotter and rainier times of year corresponding to "monsoon", "rainy", or "summer" seasons. Conclusions/SignificanceIdentifying the seasonally-dependent prevalence for diarrheal pathogens helps characterize the local epidemiology and inform the clinical diagnosis of symptomatic children. Our multi-site, multi-continent study indicates a complex epidemiology of pathogens that does not reveal an easy generalization that is consistent across all sites. Instead, our study indicates the necessity of local data to characterizing the epidemiology of diarrheal disease. Recognition of the local associations between weather conditions and pathogen prevalence suggests transmission pathways and could inform control strategies in these settings.

epidemiology↗

Blocking the Necroptosis Pathway Decreases RPE and Photoreceptor Damage Induced by NaIO3

PurposeSodium iodate (NaIO3) has been extensively used as a retinotoxin to induce RPE cell damage and degeneration of photoreceptors in vitro and in vivo. RIP-Kinase dependent programmed necrosis is an important redundant cell death pathway involved in photoreceptor cell death. We wanted to determine whether these pathways are actively involved in RPE and photoreceptor cell death after NaIO3 insult.\n\nMethodsARPE-19 cells were exposed to different concentrations of NaIO3 in the presence or absence of various concentrations of a RIPK inhibitor (Nec-1) or a pan-caspase inhibitor (Z-VAD), individually or combined. Cell death was determined at different time points by MTT (Sigma-Aldrich), LDH (Promega) and TUNEL (Millipore) assay. C57BL/6 and RIP3-/- mice were treated with a peritoneal injection of NaIO3 and eyes were enucleated at day 3 or 7. TUNEL staining was used to evaluate photoreceptor cell death. Photoreceptor cell loss was evaluated by measuring the thickness of outer nuclear layer (ONL). Microglia in the ONL were quantified in a retinal whole mount with Iba-1 antibody. RPE degeneration was also assessed in a RPE whole mount, with ZO-1 antibody.\n\nResultsNaIO3 resulted in significant cell death of ARPE-19 cells. Treatment with Nec-1 resulted in better protection than treatment with Z-VAD (P<0.01). A synergistic protective effect was observed when co-treating the cells with Nec-1 and Z-VAD. Nec-1 treatment also decreased the ARPE-19 mitochondrial damage caused by NaIO3. In vivo administration of NaIO3 resulted in significant RPE and photoreceptor destruction with substantial inflammatory cell infiltration. RIP3 knockout animals displayed considerably less RPE and photoreceptor cell loss, as well as drastically less inflammation.\n\nConclusionsProgrammed necrosis is an important cell death pathway mediating NaIO3 RPE and photoreceptor cell toxicity. Blocking the necroptosis pathway may serve as a novel therapeutic strategy for various RPE degenerative diseases.

biochemistry↗