207 research outputs found

    6-Formyl-2-meth­oxy-3-nitro­phenyl 4-toluene­sulfonate

    Get PDF
    In the title compound, C15H13NO7S, the inter­planar angle between the two aromatic rings is 26.04 (3)°. The crystal structure is stabilized by C—H⋯O interactions

    Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study

    Get PDF
    OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an established treatment for type 2 diabetes and obesity. The study objective was to establish RYGB's effects on glycemic variability (GV) and hypoglycemia. RESEARCH DESIGN AND METHODS: This was a prospective observational study of 10 participants with obesity and prediabetes or type 2 diabetes who underwent RYGB. Patients were studied before RYGB (Pre) and 1 month, 1 year, and 2 years postsurgery with continuous glucose measurement (CGM). A mixed-meal test (MMT) was conducted at Pre, 1 month, and 1 year. RESULTS: After RYGB, mean CGM decreased (at 1 month, 1 year, and 2 years), and GV increased (at 1 year and 2 years). Five of the 10 participants had a percent time in range (%TIR) <3.0 mmol/L (54 mg/dL) greater than the international consensus target of 1% at 1 or 2 years. Peak glucagon-like peptide-1 (GLP-1) and glucagon area under the curve during MMT were positively and negatively associated, respectively, with contemporaneous %TIR <3.0 mmol/L. CONCLUSIONS: Patients undergoing RYGB are at risk for development of postbariatric hypoglycemia due to a combination of reduced mean glucose, increased GV, and increased GLP-1 response

    The Distribution of Fecal Contamination in an Urbanized Tropical Lake and Incidence of Acute Diarrheal Disease

    Get PDF
    Aquatic ecosystems of tropical countries are vulnerable to fecal contamination that could cause spikes in the incidences of acute diarrheal disease (ADD) and challenge public health management systems. Vembanad lake, situated along the southwest coast of India, was monitored for one year (2018−2019). Escherichia coli, an indicator of fecal contamination, was prevalent in the lake throughout the year. Multiple antibiotic resistance among more than 50% of the E. coli isolates adds urgency to the need to control this contamination. The high abundance of E. coli and incidence of ADD were recorded during the early phase of the southwest monsoon (June−July), prior to the once-in-a-century floods that affected the region in the later phase (August). The extent of inundation in the low-lying areas peaked in August, but E. coli in the water peaked in July, suggesting that contamination occurred even prior to extreme flooding. During the COVID-19-related lockdown in March−May 2021, fecal contamination in the lake and incidence of ADD reached minimum values. These results indicate the need for improving sewage treatment facilities and city planning in flood-prone areas to avoid the mixing of septic sewage with natural waters during extreme climate events or even during the normal monsoon

    Dynamics of Vibrio cholerae in a Typical Tropical Lake and Estuarine System: Potential of Remote Sensing for Risk Mapping

    Get PDF
    Vibrio cholerae, the bacterium responsible for the disease cholera, is a naturally-occurring bacterium, commonly found in many natural tropical water bodies. In the context of the U.N. Sus�tainable Development Goals (SDG) targets on health (Goal 3), water quality (Goal 6), life under water (Goal 14), and clean water and sanitation (Goal 6), which aim to “ensure availability and sustain�able management of water and sanitation for all”, we investigated the environmental reservoirs of V. cholerae in Vembanad Lake, the largest lake in Kerala (India), where cholera is endemic. The response of environmental reservoirs of V. cholerae to variability in essential climate variables may play a pivotal role in determining the quality of natural water resources, and whether they might be safe for human consumption or not. The hydrodynamics of Vembanad Lake, and the man-made barrier that divides the lake, resulted in spatial and temporal variability in salinity (1–32 psu) and temperature (23 to 36 ◦C). The higher ends of this salinity and temperature ranges fall outside the preferred growth conditions for V. cholerae reported in the literature. The bacteria were associated with filtered water as well as with phyto- and zooplankton in the lake. Their association with benthic organisms and sediments was poor to nil. The prevalence of high laminarinase and chitinase enzyme expression (more than 50 µgmL−1 min−1 ) among V. cholerae could underlie their high association with phyto- and zooplankton. Furthermore, the diversity in the phytoplankton community in the lake, with dominance of genera such as Skeletonema sp., Microcystis sp., Aulacoseira sp., and Anabaena sp., which changed with location and season, and associated changes in the zooplankton community, could also have affected the dynamics of the bacteria in the lake. The probability of presence or absence of V. cholerae could be expressed as a function of chlorophyll concentration in the water, which suggests that risk maps for the entire lake can be generated using satellite-derived chlorophyll data. In situ observations and satellite-based extrapolations suggest that the risks from environmental V. cholerae in the lake can be quite high (with probability in the range of 0.5 to 1) everywhere in the lake, but higher values are encountered more frequently in the southern part of the lake. Remote sensing has an important role to play in meeting SDG goals related to health, water quality and life under water, as demonstrated in this example related to cholera

    Type 2 diabetes remission 2 years post Roux‐en‐Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores

    Get PDF
    AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem Type 2 diabetes remission prediction score uses HbA1c , age and Type 2 diabetes medications but not Type 2 diabetes duration. The aim of this study was to compare the predictive value of the DiaRem score with the DiaBetter score that includes Type 2 diabetes duration, upon combined (complete plus partial) 2-year post-surgery Type 2 diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and Type 2 diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with Type 2 diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a separate validation cohort study (173) were undertaken. Type 2 diabetes remission, per cent weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between per cent weight loss and Type 2 diabetes remission was investigated using logistic regression with multivariate adjustments. RESULTS: The proportion of people achieving Type 2 diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores, and lowest in those with the highest scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95% CI: 0.817-0.916); DiaRem: 0.865 (95% CI: 0.814-0.915), P = 0.856]. Two-year per cent weight loss was higher post RYGB [26.6 (95% CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95% CI: 18.3-22.8), P < 0.001]. RYGB had 151% higher odds of Type 2 diabetes CR compared with sleeve gastrectomy [OR 2.51 (95% CI: 1.12-5.60), P = 0.025]. This association became non-significant when adjusted for per cent weight loss. CONCLUSION: DiaBetter and DiaRem scores predict Type 2 diabetes remission following RYGB and sleeve gastrectomy. Two-year per cent weight loss plays a key role in determining Type 2 diabetes remission. This article is protected by copyright. All rights reserved

    Discovery of Dual-Action Membrane-Anchored Modulators of Incretin Receptors

    Get PDF
    The glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP-1) receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ligand (MTL) technology, the present study focused on defining optimized modulators of these receptors, as well as exploring how local anchoring influences soluble peptide function.Serial substitution of residue 7 in membrane-tethered GIP (tGIP) led to a wide range of activities at the GIP receptor, with [G(7)]tGIP showing enhanced efficacy compared to the wild type construct. In contrast, introduction of G(7) into the related ligands, tGLP-1 and tethered exendin-4 (tEXE4), did not affect signaling at the cognate GLP-1 receptor. Both soluble and tethered GIP and GLP-1 were selective activators of their respective receptors. Although soluble EXE4 is highly selective for the GLP-1 receptor, unexpectedly, tethered EXE4 was found to be a potent activator of both the GLP-1 and GIP receptors. Diverging from the pharmacological properties of soluble and tethered GIP, the newly identified GIP-R agonists, (i.e. [G(7)]tGIP and tEXE4) failed to trigger cognate receptor endocytosis. In an attempt to recapitulate the dual agonism observed with tEXE4, we conjugated soluble EXE4 to a lipid moiety. Not only did this soluble peptide activate both the GLP-1 and GIP receptors but, when added to receptor expressing cells, the activity persists despite serial washes.These findings suggest that conversion of a recombinant MTL to a soluble membrane anchored equivalent offers a means to prolong ligand function, as well as to design agonists that can simultaneously act on more than one therapeutic target
    corecore