Sessile serrated adenoma/polyp detection rate of water exchange, Endocuff, and cap colonoscopy: A network meta-analysis.

BACKGROUND AND AIM: Sessile serrated adenoma/polyp (SSA/P) may contribute to interval cancer. In a recent meta-analysis, water exchange (WE) was shown to be superior to Endocuff and cap colonoscopy at adenoma and advanced adenoma detection. The strong positive correlation between adenoma detection rate (ADR), advanced adenoma detection rate (AADR), and sessile serrated adenoma/polyp detection rate (SSA/PDR) prompted us to hypothesize that WE could significantly improve SSA/PDR compared with Endocuff and cap colonoscopy. METHODS: The literature was searched for all randomized controlled trials (RCTs) that reported SSA/PDR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing SSA/PDR of each method using air insufflation as the control and reported the odds ratios (ORs) with 95% confidence interval (CI). Performances were ranked based on P-score. RESULTS: A total of 531 articles resulted from initial keywords search. Eleven RCTs were included in the analysis. A total of 7856 patients underwent air insufflation, WE, Endocuff, or cap colonoscopy. WE significantly increased SSA/PDR (OR 2.04; 95% CI 1.33-3.13). Endocuff (OR 1.15; 95% CI 0.94-1.41) and cap (OR 1.08; 95% CI 0.42-2.74) did not significantly impact SSA/P detection. P-scores for WE (0.96), Endocuff (0.49), cap (0.37), and air insufflation (0.17) suggested that WE had the highest SSA/PDR. The results did not change after adjusting for mean withdrawal time and indication for colonoscopy. CONCLUSION: Water exchange significantly increases SSA/PDR and is superior to Endocuff and cap colonoscopy at detecting SSA/P.

Adenoma and Advanced Adenoma Detection Rates of Water Exchange, Endocuff, and Cap Colonoscopy: A Network Meta-Analysis with Pooled Data of Randomized Controlled Trials.

BACKGROUND AND AIMS: A network meta-analysis showed that low-cost optimization of existing resources was as effective as distal add-on devices in increasing adenoma detection rate (ADR). We assessed the impacts of water exchange (WE), Endocuff, and cap colonoscopy on ADR and advanced adenoma detection rate (AADR). We hypothesized that WE may be superior at improving ADR and AADR. METHODS: The literature was searched for all randomized controlled trials (RCTs) that reported ADR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing ADR and AADR of each method using air insufflation (AI) as the control and reported the odds ratios with 95% confidence interval. Performances were ranked based on P-score. RESULTS: Twenty-one RCTs met inclusion criteria. Fourteen RCTs also reported AADR. Both WE [1.46 (1.20-1.76)] and Endocuff [1.39 (1.17-1.66)] significantly increase ADR, while cap has no impact on ADR [1.00 (0.82-1.22)]. P-scores for WE (0.88), Endocuff (0.79), cap (0.17), and AI (0.17) suggest WE has the highest ADR. WE [1.38 (1.12-1.70)], but not Endocuff [0.96 (0.76-1.21)] or cap [1.06 (0.85-1.32)], significantly increases AADR. P-scores for WE (0.98), cap (0.50), AI (0.31), and Endocuff (0.21) suggest WE is more effective at increasing AADR. The results did not change after adjusting for age, proportion of males, and withdrawal time. CONCLUSION: WE may be the modality of choice to maximally improve ADR and AADR.

Structure and function of enterotoxigenic Escherichia coli fimbriae from differing assembly pathways.

Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here, we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared with colonization factor antigen I (CFA/I) fimbriae, which are two ETEC fimbriae assembled via different pathways, and with P-fimbriae from uropathogenic E. coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology.

Biogeochemical controls on the product of microbial U(VI) reduction.

Biologically mediated immobilization of radionuclides in the subsurface is a promising strategy for the remediation of uranium-contaminated sites. During this process, soluble U(VI) is reduced by indigenous microorganisms to sparingly soluble U(IV). The crystalline U(IV) phase uraninite, or UO2, is the preferable end-product of bioremediation due to its relatively high stability and low solubility in comparison to biomass-associated nonuraninite U(IV) species that have been reported in laboratory and under field conditions. The goal of this study was to delineate the geochemical conditions that promote the formation of nonuraninite U(IV) versus uraninite and to decipher the mechanisms of its preferential formation. U(IV) products were prepared under varying geochemical conditions and characterized with X-ray absorption spectroscopy (XAS), scanning transmission X-ray microscopy (STXM), and various wet chemical methods. We report an increasing fraction of nonuraninite U(IV) species with decreasing initial U concentration. Additionally, the presence of several common groundwater solutes (sulfate, silicate, and phosphate) promote the formation of nonuraninite U(IV). Our experiments revealed that the presence of those solutes promotes the formation of bacterial extracellular polymeric substances (EPS) and increases bacterial viability, suggesting that the formation of nonuraninite U(IV) is due to a biological response to solute presence during U(VI) reduction. The results obtained from this laboratory-scale research provide insight into biogeochemical controls on the product(s) of uranium reduction during bioremediation of the subsurface.

Secondary Kwashiorkor Disease in a Patient with Gastric Bypass Surgery and Short Gut Syndrome.

BACKGROUND Kwashiorkor disease is a subtype of severe acute protein malnutrition characterized by peripheral edema associated with hypoalbuminemia and ascites. It can result from both protein deficiency and protein loss. In resource-poor countries, the disease often is caused by inadequate dietary intake, but in resource-rich countries, it can be seen as a rare complication of severe malabsorption. CASE REPORT We present the case of a 60-year-old woman who presented with 1 week of progressive anasarca in the setting of decreased dietary intake and poor tolerance of total parenteral nutrition (TPN). She had a history of Roux-en-Y gastric bypass surgery which was complicated by a strangulated internal hernia that required an exploratory laparotomy and small bowel resection. She subsequently developed short gut syndrome with TPN dependence. Work-up revealed hypoalbuminemia with several micronutrient deficiencies consistent with secondary kwashiorkor disease. With a multidisciplinary approach that included Gastroenterology, Pharmacy, and Nutrition, she was treated with albumin, furosemide, nutritional supplementation, and ultimately rechallenged with TPN. At discharge, her swelling had improved, her weight had decreased, and her albumin improved to the normal range. CONCLUSIONS This case is a unique presentation of secondary kwashiorkor disease. In our patient, the combination of gastric bypass surgery and short gut syndrome with poor TPN tolerance likely led to severe protein malabsorption. This underscores the importance of recognizing the signs and symptoms of kwashiorkor disease and understanding the associated complications so that treatment can be instituted promptly. Furthermore, the case demonstrates how an interdisciplinary approach to management can increase the chance of a successful outcome.

A review of water exchange and artificial intelligence in improving adenoma detection.

Water exchange (WE) and artificial intelligence (AI) have made critical advances during the past decade. WE significantly increases adenoma detection and AI holds the potential to help endoscopists detect more polyps and adenomas. We performed an electronic literature search on PubMed using the following keywords: water-assisted and water exchange colonoscopy, adenoma and polyp detection, artificial intelligence, deep learning, neural networks, and computer-aided colonoscopy. We reviewed relevant articles published in English from 2010 to May 2020. Additional articles were searched manually from the reference lists of the publications reviewed. We discussed recent advances in both WE and AI, including their advantages and limitations. AI may mitigate operator-dependent factors that limit the potential of WE. By increasing bowel cleanliness and improving visualization, WE may provide the platform to optimize the performance of AI for colonoscopies. The strengths of WE and AI may complement each other in spite of their weaknesses to maximize adenoma detection.

Alcohol use disorder treatment and outcomes among hospitalized adults with alcoholic hepatitis.

Purpose: : The burden of alcohol-associated liver disease (ALD) in the United States (US) has continued to worsen in the background of rising rates of alcohol use disorder. Patients with ALD present to care at a late stage, often with the sequela of liver decompensation, such as gastrointestinal bleeding and infection. ALD is now the leading indication for liver transplantation. We aimed to measure the quality of care delivered to hospitalized patients with alcoholic hepatitis (AH) across 3 domains: 1) alcohol-use disorder (AUD) care, 2) inpatient cirrhosis care, and 3) alcohol-associated liver disease (ALD) care-and observe associations between quality of care and outcomes. Methods: : We included hospital encounters between January 1, 2016 and January 1, 2019 to a large, diverse integrated health system for AH with active alcohol use within the prior 60 days. The diagnosis of AH was determined based on previously published clinical and laboratory criteria. Quality indicator (QI) pass rates were calculated as the proportion of patients eligible for each indicator who received the QI within the timeframe specified. We then evaluated the association between the receipt of all QIs and 6-month mortality, as well as AUD-specific QIs and 30-day readmission. Results: : Of the 179 patients, the median age was 47 years-old, 59.2% were male and 49.2% were non-Hispanic White. The median Model for End-Stage Liver Disease-Sodium score was 25, while the median discriminant function was 33. Patients were followed for an average of 21 months. Overall, 14% of patients died during the index hospitalization while 17.3% died following discharge and 24.8% were re-admitted within 30-days. QI pass-rates were variable across the different domains. Few patients received AUD care-pass rates for receipt of pharmacotherapy and behavioral therapy at 6 months were only 19.1% and 35.1%, respectively. There was a significant association between receiving behavioral therapy and 6-month mortality-3% vs 18%, p = 0.05. Conclusion: : The quality of care received during hospital encounters for AH is variable, and AUD-specific therapy is low. Future quality of care initiatives are warranted to link patients to AUD treatment to ensure optimal care and maximize patients survival in this at-risk population.

Direct-acting Antiviral Therapy Improves the Outcome of Chronic Hepatitis C/intermediate-stage B Hepatocellular Carcinoma Patients.

BACKGROUND/AIM: The benefit of direct-acting antiviral therapy (DAA) in chronic hepatitis C (CHC) infected patients who received curative treatment for early-stage hepatocellular carcinoma (HCC) is well known, but is unclear for intermediate stage HCC. PATIENTS AND METHODS: CHC patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC receiving chemoembolization were identified. Univariate, multivariate analyses, and Kaplan-Meier curve were used to identify factors associated with survival outcomes. RESULTS: Among 113 included patients, the median survival of DAA treated group (n=14) and non-treated group (n=99) were 40.1 months and 22.9 months, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score, DAA, and serum albumin were key independent factors associated with overall survival. Moreover, the time-to-complete remission (TTCR) was improved in the DAA treated group. CONCLUSION: ECOG, DAA, and serum albumin were prognostic factors for CHC/intermediate-stage HCC patients. DAA was also a beneficial factor for TTCR.

Gastroenterology visitation and reminders predict surveillance uptake for patients with adenomas with high-risk features.

Individuals diagnosed with colorectal adenomas with high-risk features during screening colonoscopy have increased risk for the development of subsequent adenomas and colorectal cancer. While US guidelines recommend surveillance colonoscopy at 3 years in this high-risk population, surveillance uptake is suboptimal. To inform future interventions to improve surveillance uptake, we sought to assess surveillance rates and identify facilitators of uptake in a large integrated health system. We utilized a cohort of patients with a diagnosis of ≥ 1 tubular adenoma (TA) with high-risk features (TA ≥ 1 cm, TA with villous features, TA with high-grade dysplasia, or ≥ 3 TA of any size) on colonoscopy between 2013 and 2016. Surveillance colonoscopy completion within 3.5 years of diagnosis of an adenoma with high-risk features was our primary outcome. We evaluated surveillance uptake over time and utilized logistic regression to detect factors associated with completion of surveillance colonoscopy. The final cohort was comprised of 405 patients. 172 (42.5%) patients successfully completed surveillance colonoscopy by 3.5 years. Use of a patient reminder (telephone, electronic message, or letter) for due surveillance (adjusted odds = 1.9; 95%CI = 1.2-2.8) and having ≥ 1 gastroenterology (GI) visit after diagnosis of an adenoma with high-risk features (adjusted odds = 2.6; 95%CI = 1.6-4.2) significantly predicted surveillance colonoscopy completion at 3.5 years. For patients diagnosed with adenomas with high-risk features, surveillance colonoscopy uptake is suboptimal and frequently occurs after the 3-year surveillance recommendation. Patient reminders and visitation with GI after index colonoscopy are associated with timely surveillance completion. Our findings highlight potential health system interventions to increase timely surveillance uptake for patients diagnosed with adenomas with high-risk features.

Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.

Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance (p < 0.033) and a trend of enrichment in Bacteroidetes (p < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group (p < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses.

Health benefit of vegetable/fruit juice-based diet: Role of microbiome.

The gut microbiota is an important contributor to human health. Vegetable/fruit juices provide polyphenols, oligosaccharides, fiber and nitrate (beet juice), which may induce a prebiotic-like effect. Juice-based diets are becoming popular. However, there is a lack of scientific evidence of their health benefits. It was our hypothesis that changes in the intestinal microbiota induced by a juice-based diet play an important role in their health benefits. Twenty healthy adults consumed only vegetable/fruit juices for 3 days followed by 14 days of customary diet. On day 4 we observed a significant decrease in weight and body mass index (p = 2.0E-05), which was maintained until day 17 (p = 3.0E-04). On day 4 the proportion of the phylum Firmicutes and Proteobacteria in stool was significantly decreased and Bacteroidetes and Cyanobacteria was increased compared to baseline and was partially reversed on day 17. On day 4 plasma and urine nitric oxide was increased by 244 ± 89% and 450 ± 360%, respectively, and urinary lipid peroxidation marker malondialdehyde was decreased by 32 ± 21% compared to baseline. General well-being score was increased at the end of the study. In summary a 3-day juice-based diet altered the intestinal microbiota associated with weight loss, increase in the vasodilator NO, and decrease in lipid oxidation.

Optical High Content Nanoscopy of Epigenetic Marks Decodes Phenotypic Divergence in Stem Cells.

While distinct stem cell phenotypes follow global changes in chromatin marks, single-cell chromatin technologies are unable to resolve or predict stem cell fates. We propose the first such use of optical high content nanoscopy of histone epigenetic marks (epi-marks) in stem cells to classify emergent cell states. By combining nanoscopy with epi-mark textural image informatics, we developed a novel approach, termed EDICTS (Epi-mark Descriptor Imaging of Cell Transitional States), to discern chromatin organizational changes, demarcate lineage gradations across a range of stem cell types and robustly track lineage restriction kinetics. We demonstrate the utility of EDICTS by predicting the lineage progression of stem cells cultured on biomaterial substrates with graded nanotopographies and mechanical stiffness, thus parsing the role of specific biophysical cues as sensitive epigenetic drivers. We also demonstrate the unique power of EDICTS to resolve cellular states based on epi-marks that cannot be detected via mass spectrometry based methods for quantifying the abundance of histone post-translational modifications. Overall, EDICTS represents a powerful new methodology to predict single cell lineage decisions by integrating high content super-resolution nanoscopy and imaging informatics of the nuclear organization of epi-marks.

Combined scanning transmission X-ray and electron microscopy for the characterization of bacterial endospores.

Endospores (also referred to as bacterial spores) are bacterial structures formed by several bacterial species of the phylum Firmicutes. Spores form as a response to environmental stress. These structures exhibit remarkable resistance to harsh environmental conditions such as exposure to heat, desiccation, and chemical oxidants. The spores include several layers of protein and peptidoglycan that surround a core harboring DNA as well as high concentrations of calcium and dipicolinic acid (DPA). A combination of scanning transmission X-ray microscopy, scanning transmission electron microscopy, and energy dispersive spectroscopy was used for the direct quantitative characterization of bacterial spores. The concentration and localization of DPA, Ca(2+) , and other elements were determined and compared for the core and cortex of spores from two distinct genera: Bacillus subtilis and Desulfotomaculum reducens. This micro-spectroscopic approach is uniquely suited for the direct study of individual bacterial spores, while classical molecular and biochemical methods access only bulk characteristics.

Characterization of the surfaceome of the metal-reducing bacterium Desulfotomaculum reducens.

Desulfotomaculum reducens strain MI-1 is a Gram-positive, sulfate-reducing bacterium also capable of reducing Fe(III). Metal reduction in Gram-positive bacteria is poorly understood. Here, we investigated Fe(III) reduction with lactate, a non-fermentable substrate, as the electron donor. Lactate consumption is concomitant to Fe(III) reduction, but does not support significant growth, suggesting that little energy can be conserved from this process and that it may occur fortuitously. D. reducens can reduce both soluble [Fe(III)-citrate] and insoluble (hydrous ferric oxide, HFO) Fe(III). Because physically inaccessible HFO was not reduced, we concluded that reduction requires direct contact under these experimental conditions. This implies the presence of a surface exposed reductase capable of transferring electrons from the cell to the extracellular electron acceptor. With the goal of characterizing the role of surface proteins in D. reducens and of identifying candidate Fe(III) reductases, we carried out an investigation of the surface proteome (surfaceome) of D. reducens. Cell surface exposed proteins were extracted by trypsin cell shaving or by lysozyme treatment, and analyzed by liquid chromatography-tandem mass spectrometry. This investigation revealed that the surfaceome fulfills many functions, including solute transport, protein export, maturation and hydrolysis, peptidoglycan synthesis and modification, and chemotaxis. Furthermore, a few redox-active proteins were identified. Among these, three are putatively involved in Fe(III) reduction, i.e., a membrane-bound hydrogenase 4Fe-4S cluster subunit (Dred_0462), a heterodisulfide reductase subunit A (Dred_0143) and a protein annotated as alkyl hydroperoxide reductase but likely functioning as a thiol-disulfide oxidoreductase (Dred_1533).

Neurokinin B induces c-fos transcription via protein kinase C and activation of serum response factor and Elk-1 in immortalized GnRH neurons.

Mutations in neurokinin B (NKB) and its receptor, NK3R, were identified in human patients with hypogonadotropic hypogonadism, a disorder characterized by lack of puberty and infertility. Further studies have suggested that NKB acts at the level of the hypothalamus to control GnRH neuron activity, either directly or indirectly. We recently reported that treatment with senktide, a NK3R agonist, induced GnRH secretion and expression of c-fos mRNA in GT1-7 cells. Here, we map the responsive region in the murine c-fos promoter to between -400 and -200 bp, identify the signal transducer and activator of transcription (STAT) (-345) and serum response element (-310) sites as required for induction, a modulatory role for the Ets site (-318), and show that induction is protein kinase C dependent. Using gel shift and Gal4 assays, we further show that phosphorylation of Elk-1 leads to binding to DNA in complex with serum response factor at serum response element and Ets sites within the c-fos promoter. Thus, we determine molecular mechanisms involved in NKB regulation of c-fos induction, which may play a role in modulation of GnRH neuron activation.

Neurokinin B causes acute GnRH secretion and repression of GnRH transcription in GT1-7 GnRH neurons.

Genetic studies in human patients with idiopathic hypogonadotropic hypogonadism (IHH) identified mutations in the genes that encode neurokinin B (NKB) and the neurokinin 3 receptor (NK3R). However, determining the mechanism whereby NKB regulates gonadotropin secretion has been difficult because of conflicting results from in vivo studies investigating the luteinizing hormone (LH) response to senktide, a NK3R agonist. NK3R is expressed in a subset of GnRH neurons and in kisspeptin neurons that are known to regulate GnRH secretion. Thus, one potential source of inconsistency is that NKB could produce opposing direct and indirect effects on GnRH secretion. Here, we employ the GT1-7 cell model to elucidate the direct effects of NKB on GnRH neuron function. We find that GT1-7 cells express NK3R and respond to acute senktide treatment with c-Fos induction and increased GnRH secretion. In contrast, long-term senktide treatment decreased GnRH secretion. Next, we focus on the examination of the mechanism underlying the long-term decrease in secretion and determine that senktide treatment represses transcription of GnRH. We further show that this repression of GnRH transcription may involve enhanced c-Fos protein binding at novel activator protein-1 (AP-1) half-sites identified in enhancer 1 and the promoter, as well as chromatin remodeling at the promoter of the GnRH gene. These data indicate that NKB could directly regulate secretion from NK3R-expressing GnRH neurons. Furthermore, whether the response is inhibitory or stimulatory toward GnRH secretion could depend on the history or length of exposure to NKB because of a repressive effect on GnRH transcription.