Obesity and risk of death or dialysis in younger and older patients on specialized pre-dialysis care

Obesity is associated with increased mortality and accelerated decline in kidney function in the general population. Little is known about the effect of obesity in younger and older pre-dialysis patients. The aim of this study was to assess the extent to which obesity is a risk factor for death or progression to dialysis in younger and older patients on specialized pre-dialysis care.In a multicenter Dutch cohort study, 492 incident pre-dialysis patients (>18y) were included between 2004-2011 and followed until start of dialysis, death or October 2016. We grouped patients into four categories of baseline body mass index (BMI): <20, 20-24 (reference), 25-29, and ≥30 (obesity) kg/m2 and stratified patients into two age categories (<65y or ≥65y).The study population comprised 212 patients younger than 65 years and 280 patients 65 years and older; crude cumulative risk of dialysis and mortality at the end of follow-up were 66% and 4% for patients <65y and 64% and 14%, respectively, for patients ≥65y. Among the <65y patients, the age-sex standardized combined outcome rate was 2.3 times higher in obese than those with normal BMI, corresponding to an excess rate of 35 events/100 patient-years. After multivariable adjustment the hazard ratios (HR) (95% CI) for the combined endpoint by category of increasing BMI were, for patients <65y, 0.92 (0.41-2.09), 1 (reference), 1.76 (1.16-2.68), and 1.81 (1.17-2.81). For patients ≥65y the BMI-specific HRs were 1.73 (0.97-3.08), 1 (reference), 1.25 (0.91-1.71) and 1.30 (0.79-1.90). In the competing risk analysis, taking dialysis as the event of interest and death as a competing event, the BMI-specific multivariable adjusted subdistribution HRs (95% CI) were, for patients <65y, 0.90 (0.38-2.12), 1 (reference), 1.47 (0.96-2.24) and 1.72 (1.15-2.59). For patients ≥65y the BMI-specific SHRs (95% CI) were 1.68 (0.93-3.02), 1 (reference), 1.50 (1.05-2.14) and 1.80 (1.23-2.65).We found that obesity in younger pre-dialysis patients and being underweight in older pre-dialysis patients are risk factors for starting dialysis and for death, compared with those with a normal BMI

Co-evolution of eukaryotes and ocean oxygenation in the Neoproterozoic era

The Neoproterozoic era (about 1,000 to 542 million years ago) was a time of turbulent environmental change. Large fluctuations in the carbon cycle were associated with at least two severe-possible Snowball Earth-glaciations. There were also massive changes in the redox state of the oceans, culminating in the oxygenation of much of the deep oceans. Amid this environmental change, increasingly complex life forms evolved. The traditional view is that a rise in atmospheric oxygen concentrations led to the oxygenation of the ocean, thus triggering the evolution of animals. We argue instead that the evolution of increasingly complex eukaryotes, including the first animals, could have oxygenated the ocean without requiring an increase in atmospheric oxygen. We propose that large eukaryotic particles sank quickly through the water column and reduced the consumption of oxygen in the surface waters. Combined with the advent of benthic filter feeding, this shifted oxygen demand away from the surface to greater depths and into sediments, allowing oxygen to reach deeper waters. The decline in bottom-water anoxia would hinder the release of phosphorus from sediments, potentially triggering a potent positive feedback: phosphorus removal from the ocean reduced global productivity and ocean-wide oxygen demand, resulting in oxygenation of the deep ocean. That, in turn, would have further reinforced eukaryote evolution, phosphorus removal and ocean oxygenation

De-escalation techniques in various settings

Introduction. Severe mental disorders represent a risk factor for violent episodes. Aggressiveness and violence can be expressed verbally or behaviorally, and aggression events may occur in different clinical settings during any stage of mental disorder’s course. We sought to define a set of communication techniques and guidelines in order to improve prevention and reduce aggressive and violent episodes’ damage risk in mental healthcare. De-escalation is conceived as a process comprising the ability to gradually resolve a potentially violent situation. It consists of different steps of communication, both verbal and nonverbal, aimed to defuse a potentially violent situation. Neurobiological correlates. De-escalation acts on potential aggressive manifestations which are influenced by common neurophysiological underpinnings: these neurobiological correlates involve the HPA axis (hypothalamic-pituitary-adrenal axis) which is strongly associated with stress reaction, leading to a profound cortisol release and activation of neurotransmitter pathways and hormonal systems. Techniques and methods. Structured procedures involving different communication techniques, based on specific clinical needs, are required. De-escalation is intended to interrupt emotional activation, to establish a relationship with the agitated individual, and to provide the opportunity to resettle a functional emotional management. Conclusions. Dysfunctional conducts and aggressive behaviors may arise from mental health issues. Mental health operators should develop communication techniques and de-escalation abilities aimed to effectively manage critical situations and prevent critical interactions or physical aggression

A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells

The zinc-finger protein A20/TNFAIP3, an inhibitor of nuclear factor-kappaB (NF-kappaB) activation, has been shown to protect MCF-7 breast carcinoma cells from TNFalpha-induced apoptosis. As estrogen receptor (ER) status is an important parameter in the development and progression of breast cancer, we analysed the effect of 17beta-estradiol (E2) treatment on the expression of A20. We found that A20 is a new E2-regulated gene, whose expression correlates with ER expression in both cell lines and tumor samples. With the aim of investigating the impact of A20 expression on MCF-7 cells in response to ER ligands, we established stably transfected-MCF-7 cells overexpressing A20 (MCF-7-A20). These cells exhibited a phenotype of resistance to the 4-hydroxy-tamoxifen cytostatic and pro-apoptotic actions and of hyper-response to E2. Dysregulations in bax, bcl2, bak, phospho-bad, cyclin D1, cyclin E2, cyclin D2 and cyclin A2 proteins expression were shown to be related to the resistant phenotype developed by the MCF-7-A20 cells. Interestingly, we found that A20 was also overexpressed in MVLN and VP tamoxifen-resistant cell lines. Furthermore, high A20 expression levels were observed in more aggressive breast tumors (ER-negative, progesterone receptor-negative and high histological grade). These overall findings strongly suggest that A20 is a key protein involved in tamoxifen resistance, and thus represents both a new breast cancer marker and a promising target for developing new strategies to prevent the emergence of acquired mechanisms of drug resistance in breast cancer