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BackgroundThe COVID-19 pandemic disrupted medical care in the US, leading to a significant drop in utilization of some types of health services. We sought to quantify how the pandemic influenced obstetrics and gynecology care at two large health care organizations.Materials and methodsComparing 2020 to 2019, we quantified changes to obstetrics and gynecology care at two large health care organizations in the United States, Allegheny Health Network (in western Pennsylvania) and Johns Hopkins University (in Maryland). The analysis considered the numbers of surgical encounters, in-person visits, and telemedicine visits. For each system, we quantified temporal changes in surgical volume, in-person and telemedicine visits, and financial impact related to professional fee revenues. We used segmented regression to evaluate longitudinal effects.ResultsAt both institutions, the volume of care was similar in the first few months of 2020 compared to 2019 but dropped precipitously in March 2020. From April to June 2020, surgical volumes were 67% of the same period in 2019 at Allegheny Health and 48% of the same period in 2019 at Johns Hopkins. During that same interval, televisits accounted for approximately 21% of all ambulatory care at both institutions. Although surgical and ambulatory volumes recovered in the second half of 2020, annual surgical volumes in 2020 were significantly lower than 2019 at both institutions (pConclusionsObstetrical and gynecologic ambulatory visits and gynecologic surgeries were sharply reduced during the COVID-19 pandemic. Although care volumes returned to 2019 levels in late 2020, we observed an overall reduction in the volume of care provided and a 9% reduction in professional revenue for both institutions.

BackgroundWe previously reported in a cross-sectional analysis an adverse relationship between weight cycling and HDL-cholesterol but not angiographic obstructive coronary artery disease (CAD) among women undergoing coronary angiography for suspected ischemia in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE). We now examine the relationship between weight cycling and prospective adverse cardiovascular outcome in this group.Methods795 women enrolled between 1996-2001 in the WISE undergoing coronary angiography for evaluation of suspected ischemia and followed for a median of 6.0 years (interquartile range = 3.4 years). Adverse outcome was defined as a composite of all-cause death, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. Weight cycling was defined as the intentional loss of at least 10 lbs. (4.5 kgs.) at least three times during the women's lifetime.ResultsWomen (n = 224) who reported a history of weight cycling were younger; more often white and better educated compared those without this history. At baseline, women with a weight cycling history had lower HDL-C values, higher body mass index, larger waist circumferences and higher values for fasting blood sugar, but no difference in obstructive CAD prevalence or severity. There was an inverse relationship between weight cycling and adverse composite cardiovascular outcome, whereby fewer of women with a history of weight cycling experienced an adverse outcome as compared to non-cyclers (21% vs 29%, respectively, p = 0.03).ConclusionsDespite an adverse association with HDL-cholesterol in women undergoing coronary angiography for suspected ischemia, weight cycling was associated with a lower adverse outcome rate in women with suspected ischemia.

BACKGROUND:Community water supplies in underserved areas of the United States may be associated with increased microbiological contamination and risk of gastrointestinal disease. Microbial and health risks affecting such systems have not been systematically characterized outside outbreak investigations. The objective of the study was to evaluate associations between self-reported gastrointestinal illnesses (GII) and household-level water supply characteristics. METHODS:We conducted a cross-sectional study of water quality, water supply characteristics, and GII in 906 households served by 14 small and medium-sized community water supplies in Alabama's underserved Black Belt region. RESULTS:We identified associations between respondent-reported water supply interruption and any symptoms of GII (adjusted odds ratio (aOR): 3.01, 95% confidence interval (CI) = 1.65-5.49), as well as low water pressure and any symptoms of GII (aOR: 4.51, 95% CI = 2.55-7.97). We also identified associations between measured water quality such as lack of total chlorine and any symptoms of GII (aOR: 5.73, 95% CI = 1.09-30.1), and detection of E. coli in water samples and increased reports of vomiting (aOR: 5.01, 95% CI = 1.62-15.52) or diarrhea (aOR: 7.75, 95% CI = 2.06-29.15). CONCLUSIONS:Increased self-reported GII was associated with key water system characteristics as measured at the point of sampling in a cross-sectional study of small and medium water systems in rural Alabama in 2012 suggesting that these water supplies can contribute to endemic gastro-intestinal disease risks. Future studies should focus on further characterizing and managing microbial risks in systems facing similar challenges.

Marine diseases are of increasing concern for coral reef ecosystems, but often their causes, dynamics and impacts are unknown. The current study investigated the epidemiology of Aplysina Red Band Syndrome (ARBS), a disease affecting the Caribbean sponge Aplysina cauliformis, at both the individual and population levels. The fates of marked healthy and ARBS-infected sponges were examined over the course of a year. Population-level impacts and transmission mechanisms of ARBS were investigated by monitoring two populations of A. cauliformis over a three year period using digital photography and diver-collected data, and analyzing these data with GIS techniques of spatial analysis. In this study, three commonly used spatial statistics (Ripley's K, Getis-Ord General G, and Moran's Index) were compared to each other and with direct measurements of individual interactions using join-counts, to determine the ideal method for investigating disease dynamics and transmission mechanisms in this system. During the study period, Hurricane Irene directly impacted these populations, providing an opportunity to assess potential storm effects on A. cauliformis and ARBS.Infection with ARBS caused increased loss of healthy sponge tissue over time and a higher likelihood of individual mortality. Hurricane Irene had a dramatic effect on A. cauliformis populations by greatly reducing sponge biomass on the reef, especially among diseased individuals. Spatial analysis showed that direct contact between A. cauliformis individuals was the likely transmission mechanism for ARBS within a population, evidenced by a significantly higher number of contact-joins between diseased sponges compared to random. Of the spatial statistics compared, the Moran's Index best represented true connections between diseased sponges in the survey area. This study showed that spatial analysis can be a powerful tool for investigating disease dynamics and transmission in a coral reef ecosystem.

Marine sponges can associate with abundant and diverse consortia of microbial symbionts. However, associated bacteria remain unexamined for the majority of host sponges and few studies use phylogenetic metrics to quantify symbiont community diversity. DNA fingerprinting techniques, such as terminal restriction fragment length polymorphisms (T-RFLP), might provide rapid profiling of these communities, but have not been explicitly compared to traditional methods.We investigated the bacterial communities associated with the marine sponges Hymeniacidon heliophila and Haliclona tubifera, a sympatric tunicate, Didemnum sp., and ambient seawater from the northern Gulf of Mexico by combining replicated clone libraries with T-RFLP analyses of 16S rRNA gene sequences. Clone libraries revealed that bacterial communities associated with the two sponges exhibited lower species richness and lower species diversity than seawater and tunicate assemblages, with differences in species composition among all four source groups. T-RFLP profiles clustered microbial communities by source; individual T-RFs were matched to the majority (80.6%) of clone library sequences, indicating that T-RFLP analysis can be used to rapidly profile these communities. Phylogenetic metrics of community diversity indicated that the two sponge-associated bacterial communities include dominant and host-specific bacterial lineages that are distinct from bacteria recovered from seawater, tunicates, and unrelated sponge hosts. In addition, a large proportion of the symbionts associated with H. heliophila were shared with distant, conspecific host populations in the southwestern Atlantic (Brazil).The low diversity and species-specific nature of bacterial communities associated with H. heliophila and H. tubifera represent a distinctly different pattern from other, reportedly universal, sponge-associated bacterial communities. Our replicated sampling strategy, which included samples that reflect the ambient environment, allowed us to differentiate resident symbionts from potentially transient or prey bacteria. Pairing replicated clone library construction with rapid community profiling via T-RFLP analyses will greatly facilitate future studies of sponge-microbe symbioses.

Parkinson disease (PD) involves progressive neurodegeneration, including loss of dopamine (DA) neurons from the substantia nigra. Select genes associated with rare familial forms of PD function in cellular pathways, such as the ubiquitin-proteasome system (UPS), involved in protein degradation. The misfolding and accumulation of proteins, such as alpha-synuclein, into inclusions termed Lewy Bodies represents a clinical hallmark of PD. Given the predominance of sporadic PD among patient populations, environmental toxins may induce the disease, although their nature is largely unknown. Thus, an unmet challenge surrounds the discovery of causal or contributory neurotoxic factors that could account for the prevalence of sporadic PD. Bacteria within the order Actinomycetales are renowned for their robust production of secondary metabolites and might represent unidentified sources of environmental exposures. Among these, the aerobic genera, Streptomyces, produce natural proteasome inhibitors that block protein degradation and may potentially damage DA neurons. Here we demonstrate that a metabolite produced by a common soil bacterium, S. venezuelae, caused DA neurodegeneration in the nematode, Caenorhabditis elegans, which increased as animals aged. This metabolite, which disrupts UPS function, caused gradual degeneration of all neuronal classes examined, however DA neurons were particularly vulnerable to exposure. The presence of DA exacerbated toxicity because neurodegeneration was attenuated in mutant nematodes depleted for tyrosine hydroxylase (TH), the rate-limiting enzyme in DA production. Strikingly, this factor caused dose-dependent death of human SH-SY5Y neuroblastoma cells, a dopaminergic line. Efforts to purify the toxic activity revealed that it is a highly stable, lipophilic, and chemically unique small molecule. Evidence of a robust neurotoxic factor that selectively impacts neuronal survival in a progressive yet moderate manner is consistent with the etiology of age-associated neurodegenerative diseases. Collectively, these data suggest the potential for exposures to the metabolites of specific common soil bacteria to possibly represent a contributory environmental component to PD.

The study of protein-protein interactions is becoming increasingly important for understanding the regulation of many cellular processes. The ability to quantify the strength with which two binding partners interact is desirable but the accurate determination of equilibrium binding constants is a difficult process. The use of Luminescence Resonance Energy Transfer (LRET) provides a homogeneous binding assay that can be used for the detection of protein-protein interactions. Previously, we developed an LRET assay to screen for small molecule inhibitors of the interaction of sigma70 with thebeta' coiled-coil fragment (amino acids 100-309). Here we describe an LRET binding assay used to monitor the interaction of E. coli sigma70 and sigma32 with core RNA polymerase along with the controls to verify the system. This approach generates fluorescently labeled proteins through the random labeling of lysine residues which enables the use of the LRET assay for proteins for which the creation of single cysteine mutants is not feasible. With the LRET binding assay, we are able to show that the interaction of sigma70 with core RNAP is much more sensitive to NaCl than to potassium glutamate (KGlu), whereas the sigma32 interaction with core RNAP is insensitive to both salts even at concentrations >500 mM. We also find that the interaction of sigma32 with core RNAP is stronger than sigma70 with core RNAP, under all conditions tested. This work establishes a consistent set of conditions for the comparison of the binding affinities of the E.coli sigma factors with core RNA polymerase. The examination of the importance of salt conditions in the binding of these proteins could have implications in both in vitro assay conditions and in vivo function.