• Herrera Carr posted an update 6 months ago

    MALAT1 rs3200401 increases GC susceptibility and might affect GC development. Further studies are needed to validate our results in large populations and different ethnic groups.Studies suggest a link between the gut microbiome and metastatic renal cell carcinoma (mRCC) outcomes, including evidence that mRCC patients possess a lower abundance of Bifidobacterium spp. compared to healthy adults. EZM0414 in vivo We sought to assess if a Bifidobacterium-containing yogurt product could modulate the gut microbiome and clinical outcome from vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs). mRCC patients initiating VEGF-TKIs, regardless of the line of therapy, were randomized to probiotic-supplemented (two 4 oz. servings of the probiotic yogurt product daily) or probiotic-restricted arms. Stool samples were collected prior to therapy and at weeks 2, 3, 4, and 12. Microbiome composition was assessed using whole-metagenome sequencing. A total of 20 patients were randomized. Bifidobacterium animalis, the active ingredient of the probiotic supplement, reached detectable levels in all patients in the probiotic-supplemented arm versus two patients in the probiotic-restricted arm. Clinical benefit rate was similar in probiotic-supplemented versus probiotic-restricted arms (70% vs. 80%, p = 0.606). Linear discriminant analysis (LDA) effect size analysis of MetaPhIAn2 abundance data predicted 25 enriched species demonstrating an LDA score >3 in either clinical benefit or no clinical benefit. In patients with clinical benefit (vs. no clinical benefit), Barnesiella intestinihominis and Akkermansia muciniphila were significantly more abundant (p = 7.4 × 10-6 and p = 5.6 × 10-3 , respectively). This is the first prospective randomized study demonstrating modulation of the gut microbiome with a probiotic in mRCC. Probiotic supplementation successfully increased the Bifidobacterium spp. levels. Analysis of longitudinal stool specimens identified an association between B. intestinihominis, A. muciniphila, and clinical benefit with therapy. Trial Registration NCT02944617.A fixed-dose combination (FDC) product of a selective sodium-glucose cotransporter 2 inhibitor ertugliflozin and immediate-release metformin is approved for type 2 diabetes mellitus in the United States, European Union countries, Canada, and other countries. Two studies were conducted to assess the bioequivalence of metformin in the ertugliflozin/metformin FDC tablets to the corresponding doses of Canadian-sourced metformin (Glucophage) coadministered with ertugliflozin. Both studies were phase 1 randomized, open-label, 2-period, single-dose crossover studies (n = 32) in which healthy subjects received an ertugliflozin/metformin FDC tablet (2.5/500 mg or 7.5/850 mg) and the respective doses of the individual components (ertugliflozin coadministered with Canadian-sourced metformin) under fasted (n = 18) or fed (n = 14) conditions. Blood samples were collected 72 hours postdose to determine metformin concentrations. The 90% confidence intervals were within the bioequivalence acceptance criteria for the adjusted geometric mean ratios (FDCcoadministered) for metformin area under the plasma concentration-time curve from time zero to time t, where t is the last point with a measurable concentration and peak observed plasma concentration for both dose strengths under fasted and fed conditions. All study medications were well tolerated. Bioequivalence was demonstrated for the metformin component of the ertugliflozin/metformin FDC tablets and the corresponding doses of the Canadian-sourced metformin coadministered with ertugliflozin.This study investigated changes in calcitonin cells (C-cells) and parathyroid glands (PTG) induced by microcystin LR (MCLR) exposure to rats and evaluated ameliorative effects of jamun (Syzygium cumini) seed (JSE) and orange (Citrus sinensis) peel (OPE) extracts. Wistar rats were treated as-Group A (control), Group B (MCLR), Group C (MCLR + JSE), Group D (MCLT + OPE), Group E (OPE) and Group F (JSE). Microcystin dose was (10 μg/kg body wt/day whereas OPE and JSE dose was 200 mg/kg body wt/day. Thyroid and PTG were fixed on 15 and 30 days following the treatment. C-cells of treated rats for 15 days with MCLR; MCLR + JSE and MCLR + OPE exhibit degranulation, mitochondrial swelling and prominent RER. In MCLR treated rats few cells completely lack secretory granules. After 30 days MCLR treatment accumulation of secretory granules and degeneration were noticed in C-cells. C-cell nuclear volume (NV) of MCLR, MCLR + JSE and MCLT + OPE treated rats show an increase. In MCLR, MCLR + JSE and MCLR + OPE treated rats PTG exhibit hyperchromatic nuclei, nuclear elongation and increased NV after 15 days. After 30 days MCLR treatment nuclei of PTG become more hyperchromatic, more elongated, show degeneration of nuclei and increase in NV. NV is increased in Group C and Group D. PTG remain unaltered 30 days following treatment with OPE and JSE. Microcystin LR provoke physiological effects on the blood calcium and alterations in C cells and PTG, which cause serious threat to organism. These changes can be protected by JSE and OPE.

    Registry-based studies have become more common due to the availability of a large study cohort. However, the validity of findings is dependent on the completeness of the registry. This study aimed to validate the capture rate of the New Zealand Joint Registry (NZJR) by matching procedures that have been recorded separately via clinical coding by the New Zealand Government’s National Surgical Site Infection Improvement Programme (SSIIP).

    The National Health Index, a unique identification code for all patients, was combined with the arthroplasty procedure performed (primary total knee arthroplasty (TKA), primary total hip arthroplasty (THA), revision TKA or revision THA) and operation side. Publicly funded procedures recorded in the NZJR were matched with procedures recorded by the SSIIP on a record-by-record basis. This identified the total number of arthroplasty procedures performed in New Zealand, which was used as the denominator value to calculate the procedure capture rate of the NZJR.

    Between 2013 and 2018, 24 556 primary TKA, 28 970 primary THA, 2107 revision TKA and 4263 revision THA procedures were recorded by both datasets.

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