Unusual Presentation of Von Hippel-Lindau Syndrome With Gastric Variceal Bleeding.

Gastric varices are most commonly a complication of portal hypertension or splenic vein thrombosis (SVT). The presence of gastric varices due to portal hypertension is significantly less than the prevalence of esophageal varices. SVT is a known complication of pancreatitis due to inflammation or compression of the splenic vein coursing along the posterior surface of the pancreas. Occlusion of the splenic vein leads to left-sided portal hypertension. Left-sided portal hypertension results in the development of collateral vessels that bypass the splenic vein by connecting with the short gastric veins. The associated increased pressure within the gastric vessels results in gastric varices. Gastric varices due to SVT may occur in the absence of or be disproportionate to esophageal varices. We report an interesting case of gastrointestinal bleeding from gastric varices related to cirrhosis secondary to metabolic dysfunction-associated steatohepatitis and SVT secondary to chronic pancreatitis due to pancreatic neuroendocrine tumor (NET) in a patient diagnosed with von Hippel-Lindau (VHL) syndrome.

Shedding of SARS-CoV-2 in feces and urine and its potential role in person-to-person transmission and the environment-based spread of COVID-19.

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). A review of 48 independent studies revealed that severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 102-105 gc/ml) and feces (ca. 102-107 gc/ml) is much lower than in nasopharyngeal fluids (ca. 105-1011 gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the gut and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears much lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that tens of million cases of COVID-19 have occurred globally, but exposure to feces or wastewater has never been implicated as a transmission vector.

Structure and Role of BCOR PUFD in Noncanonical PRC1 Assembly and Disease.

Polycomb repression complex 1 (PRC1) is a multiprotein assembly that regulates transcription. The Polycomb group ring finger 1 protein (PCGF1) is central in the assembly of the noncanonical PRC1 variant called PRC1.1 through its direct interaction with BCOR (BCL-6-interacting corepressor) or its paralog, BCOR-like 1 (BCORL1). Previous structural studies revealed that the C-terminal PUFD domain of BCORL1 is necessary and sufficient to heterodimerize with the RAWUL domain of PCGF1 and, together, form a new protein-protein binding interface that associates with the histone demethylase KDM2B. Here, we show that the PUFD of BCOR and BCORL1 differ in their abilities to assemble with KDM2B. Unlike BCORL1, the PUFD of BCOR alone does not stably assemble with KDM2B. Rather, additional residues N-terminal to the BCOR PUFD are necessary for stable association. Nuclear magnetic resonance (NMR) structure determination and 15N T2 relaxation time measurements of the BCOR PUFD alone indicate that the termini of the BCOR PUFD, which are critical for binding PCGF1 and KDM2B, are disordered. This suggests a hierarchical mode of assembly whereby BCOR PUFD termini become structurally ordered upon binding PCGF1, which then allows stable association with KDM2B. Notably, BCOR internal tandem duplications (ITDs) leading to pediatric kidney and brain tumors map to the PUFD termini. Binding studies with the BCOR ITD indicate the ITD would disrupt PRC1.1 assembly, suggesting loss of the ability to assemble PRC1.1 is a critical molecular event driving tumorigenesis.

Predicted Impact of Climate Change on Trihalomethanes Formation in Drinking Water Treatment.

Quantitative predictions of impacts on public water supplies are essential for planning climate change adaptations. Monitoring data from five full-scale Scottish drinking water treatment plants (DWTPs) showed that significant correlations exist between conditionally carcinogenic trihalomethanes (THMs) levels, water temperature (r = 0.812, p = 0.0013) and dissolved organic carbon (DOC) (r = 0.892, p < 0.0001), respectively. The strong seasonality of these parameters demonstrated how climate can influence THMs formation. We quantified with laboratory experiments the sensitivity of THMs formation to changes in water temperature and DOC concentration. The laboratory data accurately reproduced real-world THM formation in the DWTPs. We then combined these validated relationships with information from the literature about future trends in mean summer temperatures and surface water DOC in the British Isles, to estimate future global warming impacts on THMs formation in DWTPs that use chlorine for disinfection. An increase in mean summer temperatures will likely increase THM formation, with a 1.8 °C temperature increase and 39% THMs increase by 2050 representing our mid-range scenario. Such an increase has major implications to potable water around the world, either an increased health risk or increased water treatment costs to maintain an equivalent quality potable supply.

Microbial community composition and diversity in rice straw digestion bioreactors with and without dairy manure.

Anaerobic digestion (AD) uses a range of substrates to generate biogas, including energy crops such as globally abundant rice straw (RS). Unfortunately, RS is high in lignocellulosic material and has high to C:N ratios (~80:1), which makes it (alone) a comparatively poor substrate for AD. Co-digestion with dairy manure (DM) has been promoted as a method for balancing C:N ratios to improve RS AD whilst also treating another farm waste and co-producing a potentially useful fertiliser. However, past co-digestion studies have not directly compared RS AD microbial communities with and without DM additions, which has made it hard to assess all impacts of DM addition to RS AD processes. Here, four RS:DM ratios were contrasted in identical semi-continuous-fed AD bioreactors, and 100% RS was found to produce the highest specific methane yields (112 mL CH4/g VS/day; VS, volatile solids), which is over double yields achieved in the reactor with the highest DM content (30:70 RS:DM by mass; 48 mL CH4/g VS/day). To underpin these data, microbial communities were sequenced and characterised across the four reactors. Dominant operational taxonomic units (OTUs) in the 100% RS unit were Bacteroidetes/Firmicutes, whereas the 30:70 RS:DM unit was dominated by Proteobacteria/Spirochaetes, suggesting major microbial community shifts occur with DM additions. However, community richness was lowest with 100% RS (despite higher specific yields), suggesting particular OTUs may be more important to yields than microbial diversity. Further, ambient VFA and VS levels were significantly higher when no DM was added, suggesting DM-amended reactors may cope better with higher organic loading rates (OLR). Results show that RS AD without DM addition is feasible, although co-digestion with DM will probably allow higher OLRs, resulting in great RS throughput in farm AD units.

Climatic, Geographic and Operational Determinants of Trihalomethanes (THMs) in Drinking Water Systems.

Trihalomethanes (THMs) are conditionally carcinogenic compounds formed during chlorine disinfection in water treatment processes around the world. THMs occur especially when source waters are subject to marine influences, high and-or regular precipitation, and elevated levels of organic matter. THMs formation is then rooted in geographic, operational and climatic factors, the relative importance of which can only be derived from large datasets and may change in the future. Ninety three full-scale Scottish water treatment plants (WTPs) were assessed from Jan 2011 to Jan 2013 to identify factors that promote THMs formation. Correlation analysis showed that ambient temperature was the primary THMs formation predictor in potable water (r2 = 0.66, p < 0.05) and water distribution systems (r2 = 0.43, p = 0.04), while dissolved organic carbon (r2 = 0.55, p < 0.001) and chloride (indicating marine influence; r2 = 0.41, p < 0.001) also affected THMs formation. GIS mapping of median THMs levels indicated brominated THMs were most prevalent in coastal areas and on islands. This real-world dataset confirms both geographic and climatic factors are key to THMs formation. If ambient temperatures increase, THMs control will become more challenging, substantiating concerns about the impact of global warming on water quality.

Dominant and novel clades of Candidatus Accumulibacter phosphatis in 18 globally distributed full-scale wastewater treatment plants.

Here we employed quantitative real-time PCR (qPCR) assays for polyphosphate kinase 1 (ppk1) and 16S rRNA genes to assess relative abundances of dominant clades of Candidatus Accumulibacter phosphatis (referred to Accumulibacter) in 18 globally distributed full-scale wastewater treatment plants (WWTPs) from six countries. Accumulibacter were not only detected in the 6 WWTPs performing biological phosphorus removal, but also inhabited in the other 11 WWTPs employing conventional activated sludge (AS) with abundances ranging from 0.02% to 7.0%. Among the AS samples, clades IIC and IID were found to be dominant among the five Accumulibacter clades. The relative abundance of each clade in the Accumulibacter lineage significantly correlated (p < 0.05) with the influent total phosphorus and chemical oxygen demand instead of geographical factors (e.g. latitude), which showed that the local wastewater characteristics and WWTPs configurations could be more significant to determine the proliferation of Accumulibacter clades in full-scale WWTPs rather than the geographical location. Moreover, two novel Accumulibacter clades (IIH and II-I) which had not been previously detected were discovered in two enhanced biological phosphorus removal (EBPR) WWTPs. The results deepened our understanding of the Accumulibacter diversity in environmental samples.

Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction.

OBJECTIVE: Peripheral insulin resistance is linked to an increase in reactive oxygen species (ROS), leading in part to the production of reactive lipid aldehydes that modify the side chains of protein amino acids in a reaction termed protein carbonylation. The primary enzymatic method for lipid aldehyde detoxification is via glutathione S-transferase A4 (GSTA4) dependent glutathionylation. The objective of this study was to evaluate the expression of GSTA4 and the role(s) of protein carbonylation in adipocyte function. RESEARCH DESIGN AND METHODS: GSTA4-silenced 3T3-L1 adipocytes and GSTA4-null mice were evaluated for metabolic processes, mitochondrial function, and reactive oxygen species production. GSTA4 expression in human obesity was evaluated using microarray analysis. RESULTS: GSTA4 expression is selectively downregulated in adipose tissue of obese insulin-resistant C57BL/6J mice and in human obesity-linked insulin resistance. Tumor necrosis factor-alpha treatment of 3T3-L1 adipocytes decreased GSTA4 expression, and silencing GSTA4 mRNA in cultured adipocytes resulted in increased protein carbonylation, increased mitochondrial ROS, dysfunctional state 3 respiration, and altered glucose transport and lipolysis. Mitochondrial function in adipocytes of lean or obese GSTA4-null mice was significantly compromised compared with wild-type controls and was accompanied by an increase in superoxide anion. CONCLUSIONS: These results indicate that downregulation of GSTA4 in adipose tissue leads to increased protein carbonylation, ROS production, and mitochondrial dysfunction and may contribute to the development of insulin resistance and type 2 diabetes.