• Levin Graham posted an update 1 year, 6 months ago

    To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM).

    A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100.

    Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE) -1.13 (0.05) % and Gla-100 -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference 0.02%, 95% CI -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed≤3.9mmol/L or severe) vs Gla-100 at any time of day or at night (0000-0559h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups.

    Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.

    Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.

    To determine the prevalence of Associated Autoimmune Diseases (AADs) in Latent Autoimmune Diabetes of Adults (LADA) versus autoimmune Type 1 Diabetes (T1D) and the role of glutamic-acid decarboxylase antibodies (GADA) and other factors.

    Adults with autoimmune diabetes mellitus (DM) were recruited from the Diabetes Center of Nikaia-Piraeus Hospital. Demographic and clinical parameters were recorded and anti-pancreatic and organ-specific antibodies were measured.

    Of 160 patients, 33.75% had one AAD and 24.37% had two or more. Patients with LADA had higher overall prevalence of AADs, mainly autoimmune thyroiditis and gastritis. Celiac disease was present only in T1D. GADA positive patients had higher prevalence of AADs and multiple autoimmunity, especially thyroiditis and gastritis. Patients with LADA had higher rates of positive GADA or islet-cell antibodies (ICA). After controlling for LADA, GADA remained a significant predictor of AADs. Female gender and chronological age were also significant predictors of AADs.

    AADs were present in 58.13% of patients. Patients with LADA were more prone to a generalized autoimmune disorder than those with T1D. AADs development was significantly associated with female sex, older age and positive GADA, which proved an independent marker of associated autoimmunity.

    AADs were present in 58.13% of patients. Patients with LADA were more prone to a generalized autoimmune disorder than those with T1D. AADs development was significantly associated with female sex, older age and positive GADA, which proved an independent marker of associated autoimmunity.Heterocyclic amines (HCAs) are a group of mutagenic compounds produced during thermal processing of protein-rich foods. One of the most abundant HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has potential carcinogenic and mutagenic effects on human organs, especially the colon. This study aimed to explore the toxic effects of PhIP on amino acid metabolism in the colon of Wistar rats using RNA-seq and LC-MS/MS. Exposure to PhIP for 4 weeks induced oxidative damage and DNA damage in the colons, and disrupted the expression of related genes involved in tryptophan metabolism, beta(β)-alanine metabolism, valine, leucine, and isoleucine degradation, and glutathione metabolic pathways. Moreover, the levels of fecal metabolites related to amino acid metabolism were affected by PhIP. Cumulatively, these results indicate that PhIP can induce colonic oxidative injury and disorders related to amino acid metabolism, thereby providing a new theoretical basis for the study of PhIP toxicity.

    Haemato-oncology patients are at increased risk of infection from atypical mycobacteria such as Mycobacterium chelonae which are commonly found in both domestic and hospital water systems.

    To describe the investigation and control measures following two patient cases of M.chelonae and positive water samples in the study hospital.

    Water testing was undertaken from outlets, storage tanks and mains supply. Whole-genome sequencing (WGS) was used to compare patient and positive water samples. The subsequent infection control measures implemented are described.

    The WGS results showed two main populations of M.chelonae within the group of sampled isolates. The results showed that the patient strains were unrelated to each other, but that the isolate from one patient was closely related to environmental samples from water outlets, supporting nosocomial acquisition.

    WGS was used to investigate two patient cases of M.chelonae and positive water samples from a hospital water supply. Relevant control measures and the potential for chemical dosing of water systems to enhance proliferation of atypical mycobacteria are discussed.

    WGS was used to investigate two patient cases of M. chelonae and positive water samples from a hospital water supply. Relevant control measures and the potential for chemical dosing of water systems to enhance proliferation of atypical mycobacteria are discussed.Invasion of bladder cancer (BC) cells from the mucosa into the muscle layer is canonical for BC progression while phospholipase D isoform 1 (PLD1) is known to mediate development of cancer through phosphatidic acid (PA) production. We therefore used in silico, in vitro and in vivo approaches to detail the effect of PLD1 on BC invasion. In BC patients, higher levels of PLD1 expression were associated with poor prognoses. PLD1 knockdown significantly suppressed cellular invasion by human BC cells and matrix metalloproteinase-13 (MMP-13) was observed to mediate this effect. In our mouse bladder carcinogenesis model, the development of invasive BCs was suppressed by PLD1 knockout and a global transcriptomic analysis in this model indicated MMP-13 as a potential tumor invasion gene with NF-κB (nuclear factor-kB) as its transcriptional regulator. find more Furthermore, PA administration increased MMP-13 expression in line with NF-κB p65 phosphorylation levels. Collectively, we demonstrate that PLD1 promotes tumor invasion of BC by regulation of MMP-13 expression through the NF-κB signaling pathway and that PLD1 might be a potential therapeutic target to prevent clinical progression in BC patients.

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