Helboraahauge0042

OBJECTIVE Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA. RESEARCH DESIGN AND METHODS Blood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea Cardiovascular End Points (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A1c (HbA1c) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded. RESULTS Median follow-up was 4.3 years. In those with preexisting diabetes (n = 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA1c, or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n = 452) or in new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable. CONCLUSIONS Among patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation. © 2020 by the American Diabetes Association.Retinal regeneration is robust in some cold-blooded vertebrates, but this process is ineffective in warm-blooded vertebrates. Understanding the mechanisms that suppress the reprogramming of Müller glia into neurogenic progenitors is key to harnessing the regenerative potential of the retina. Inflammation and reactive microglia are known to influence the formation of Müller glia-derived progenitor cells (MGPCs), but the mechanisms underlying this interaction are unknown. Indole-3-acetic acid sodium We used the chick model in vivo to investigate Nuclear Factor kappa B (NF-κB) signaling, a critical regulator of inflammation, during the reprogramming of Müller glia into proliferating progenitors. We find that components of the NF-κB pathway are dynamically regulated by Müller glia after neuronal damage or treatment with growth factors. Inhibition of NF-κB enhances, whereas activation suppresses the formation of proliferating MGPCs. Following microglia ablation, the effects of NF-κB-agonists on MGPC-formation are reversed, suggesting that signals provided by reactive microglia influence how NF-κB impacts Müller glia reprogramming. We propose that NF-κB is an important signaling "hub" that suppresses the reprogramming of Müller glia into proliferating MGPCs and this "hub" coordinates signals provided by reactive microglia. © 2020. Published by The Company of Biologists Ltd.Powerful regeneration ability enables plants survival when plants are wounded. For example, adventitious roots can regenerate from the cutting site in detached Arabidopsis thaliana leaf explants even in the absence of any exogenous plant hormone treatment. This process is known as de novo root regeneration (DNRR). Although the developmental program underlying DNRR is revealed, the precise regulatory mechanisms during DNRR are not completely understood. Here, we show that ethylene treatment or genetic activation of transcription factor ETHYLENE INSENSITIVE 3 (EIN3) strongly suppresses DNRR rates, while a mutant lacking EIN3 and its homolog EIL1 (ein3 eil1) displays a higher DNRR capacity. Previous reports have shown that the sequential induction of WUSCHEL RELATED HOMEOBOX 11 (WOX11)/WOX12 and WOX5/WOX7 expression is required for the establishment of DNRR. We found that EIN3 directly targets WOX11 and WOX5 promoter regions to suppress their transcription. Furthermore, older plants show enhanced EIN3 activity, and repressed expression of WOX11 and WOX5 Taken together, these results illustrate that plant aging at least partially takes advantage of EIN3 as a negative regulator to suppress DNRR through inhibiting the activation of WOX genes. © 2020. Published by The Company of Biologists Ltd.BACKGROUND AND OBJECTIVES Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demogtients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Deutsches Register für Klinische Studien (DRKS; German national database of clinical studies), DRKS00003971. Copyright © 2020 by the American Society of Nephrology.BACKGROUND AND OBJECTIVES Oxidative stress is a hallmark and mediator of CKD. Diminished antioxidant defenses are thought to be partly responsible. However, there is currently no way to prospectively assess antioxidant defenses in humans. Tin protoporphyrin (SnPP) induces mild, transient oxidant stress in mice, triggering increased expression of select antioxidant proteins (e.g., heme oxygenase 1 [HO-1], NAD[P]H dehydrogenase [quinone] 1 [NQO1], ferritin, p21). Hence, we tested the hypothesis that SnPP can also variably increase these proteins in humans and can thus serve as a pharmacologic "stress test" for gauging gene responsiveness and antioxidant reserves. DESIGN , setting, participants, & measurementsA total of 18 healthy volunteers and 24 participants with stage 3 CKD (n=12; eGFR 30-59 ml/min per 1.73 m2) or stage 4 CKD (n=12; eGFR 15-29 ml/min per 1.73 m2) were injected once with SnPP (9, 27, or 90 mg). Plasma and/or urinary antioxidant proteins were measured at baseline and for up to 4 days post-SnPP dosing.