Hesselbergtermansen2013

Mortality is an important outcome for all dialysis stakeholders. We examined associations between dialysis modality and mortality in the modern era.

Observational study comparing dialysis inception cohorts 1998-2002, 2003-2007, 2008-2012, and 2013-2017.

Australia and New Zealand (ANZ) dialysis population.

The primary exposure was dialysis modality facility hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), automated PD (APD), or home HD.

The main outcome was death.

Cause-specific proportional hazards models with shared frailty and subdistribution proportional hazards (Fine and Gray) models, adjusting for available confounding covariates.

In 52,097 patients, the overall death rate improved from ~15 deaths per 100 patient-years in 1998-2002 to ~11 in 2013-2017, with the largest cause-specific contribution from decreased infectious death. Relative to facility HD, mortality with CAPD and APD has improved over the years, with adjusted hazard ratios in 2013-2017 of 0.88 (95% CI, 0.782017 appears greater than the survival for patients on facility HD in ANZ. Additional research is needed to assess whether changing clinical risk profiles over time, varied dialysis prescription, and morbidity from dialysis access contribute to these findings.Previous studies have demonstrated that the activation of delta opioid receptors is neuroprotective against neonatal hypoxia-ischemia (HI) brain injury. The aim of this study was to investigate the neuroprotective effects of biphalin, a dimeric opioid peptide, in a mouse model of neonatal HI and the underlying mechanisms. On postnatal day 10, mouse pups were subjected to unilateral carotid artery ligation followed by 1 h of hypoxia (10 % O2 in N2). For treatment, biphalin (5 mg/kg, 10 mg/kg, 20 mg/kg) was administered intraperitoneally immediately after HI. The opioid antagonist naloxone or phosphatidylinositol-3-kinase inhibitor Ly294002 was administered to determine the underlying mechanisms. Infarct volume, brain edema, phosphorylated Akt and apoptosis-related proteins levels were evaluated by using a combination of 2,3,5-triphenyltetrazolium chloride staining, brain water content and Western blotting at 24 h after HI. The long-term effects of biphalin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests at 3 weeks post-HI. Biphalin (10 mg/kg) significantly reduced the infarct volume and ameliorated brain edema. Biphalin also had long-term protective effects against the loss of ipsilateral brain tissue and resulted in improvements in neurobehavioral outcomes. However, naloxone or Ly294002 abrogated the neuroprotective effects of biphalin. learn more Furthermore, biphalin treatment significantly preserved phosphorylated Akt expression, increased Bcl-2 levels, and decreased Bax and cleaved caspase 3 levels after HI. These effects were also reversed by naloxone and Ly294002 respectively. In conclusion, biphalin protects against HI brain injury in neonatal mice, which might be through activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway.Accumulated evidence from genetically modified cell and animal models indicates that centrosome amplification (CA) can initiate tumorigenesis with metastatic potential and enhance cell invasion. Multiple human diseases are associated with CA and carcinogenesis as well as metastasis, including infection with oncogenic viruses, type 2 diabetes, toxicosis by environmental pollution and inflammatory disease. In this review, we summarize (1) the evidence for the roles of CA in tumorigenesis and tumor cell invasion; (2) the association between diseases and carcinogenesis as well as metastasis; (3) the current knowledge of CA in the diseases; and (4) the signaling pathways of CA. We then give our own thinking and discuss perspectives relevant to CA in carcinogenesis and cancer metastasis in human diseases. In conclusion, investigations in this area might not only identify CA as a biological link between these diseases and the development of cancer but also prove the causal role of CA in cancer and progression under pathophysiological conditions, potentially taking cancer research into a new era.Autophagy is a highly conserved metabolic process involved in the degradation of intracellular components including proteins and organelles. Consequently, it plays a critical role in recycling metabolic energy for the maintenance of cellular homeostasis in response to various stressors. In cancer, autophagy either suppresses or promotes cancer progression depending on the stage and cancer type. Epithelial-mesenchymal transition (EMT) and cancer metastasis are directly mediated by oncogenic signal proteins including SNAI1, SLUG, ZEB1/2, and NOTCH1, which are functionally correlated with autophagy. In this report, we discuss the crosstalk between oncogenic signaling pathways and autophagy followed by possible strategies for cancer treatment via regulation of autophagy. Although autophagy affects EMT and cancer metastasis, the overall signaling pathways connecting cancer progression and autophagy are still illusive. In general, autophagy plays a critical role in cancer cell survival by providing a minimum level of energy via self-digestion. Thus, cancer cells face nutrient limitations and challenges under stress during EMT and metastasis. Conversely, autophagy acts as a potential cancer suppressor by degrading oncogenic proteins, which are essential for cancer progression, and by removing damaged components such as mitochondria to enhance genomic stability. Therefore, autophagy activators or inhibitors represent possible cancer therapeutics. We further discuss the regulation of autophagy-dependent degradation of oncogenic proteins and its functional correlation with oncogenic signaling pathways, with potential applications in cancer therapy.Sepsis-associated encephalopathy (SAE) is characterized by diffuse cerebral and central nervous system (CNS) dysfunction. Microglia play a vital role in protecting the brain from neuronal damage, which is closely related to inflammatory responses. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has an impact on microglial and neuronal injury. Here, we mainly explored the molecular mechanism by which Hydrogen (H2) regulates neuroinflammation in SAE and the role of Nrf2 in this process. An in vivo model of SAE was generated by cecal ligation and puncture (CLP). Primary microglia and neurons were cultured to establish an in vitro model. Microglia, neurons and brain tissue were obtained to detect Nrf2 expression, inflammation, cell injury, apoptosis, and microglial polarization. Escape latency, the number of platform crossings and the time spent in the target quadrant were measured to assess cognitive function. H2 attenuated microglial polarization from the M1 to the M2 phenotype, cytokine release and TLR/NF-κb activation and protected neurons from lipopolysaccharide (LPS)-activated microglia-induced injury via the Nrf2 pathway.