Polo-like kinases (Plks) are characterized by the presence of a specific domain, known as the polo box (PBD), involved in protein-protein interactions. Plk1 to Plk4 are involved in centrosome biology as well as the regulation of mitosis, cytokinesis, and cell cycle checkpoints in response to genotoxic stress. We have analyzed here the new member of the vertebrate family, Plk5, a protein that lacks the kinase domain in humans. Plk5 does not seem to have a role in cell cycle progression; in fact, it is downregulated in proliferating cells and accumulates in quiescent cells. This protein is mostly expressed in the brain of both mice and humans, and it modulates the formation of neuritic processes upon stimulation of the brain-derived neurotrophic factor (BDNF)/nerve growth factor (NGF)-Ras pathway in neurons. The human PLK5 gene is significantly silenced in astrocytoma and glioblastoma multiforme by promoter hypermethylation, suggesting a tumor suppressor function for this gene. Indeed, overexpression of Plk5 has potent apoptotic effects in these tumor cells. Thus, Plk5 seems to have evolved as a kinase-deficient PBD-containing protein with nervous system-specific functions and tumor suppressor activity in brain cancer.
Objectives: To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population. Methods: A retrospective single-center analysis (2006–2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded. Results: One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9–63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years ( P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children. Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality. Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications ( P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN). Conclusions: Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.
IntroductionAdults with end-stage kidney disease (ESKD) treated with haemodialysis experience mortality of between 15% and 20% each year. Effective interventions that improve health outcomes for long-term dialysis patients remain unproven. Novel and testable determinants of health in dialysis are needed. Nutrition and dietary patterns are potential factors influencing health in other health settings that warrant exploration in multinational studies in men and women treated with dialysis. We report the protocol of the “DIETary intake, death and hospitalisation in adults with end-stage kidney disease treated with HaemoDialysis (DIET-HD) study,” a multinational prospective cohort study. DIET-HD will describe associations of nutrition and dietary patterns with major health outcomes for adults treated with dialysis in several countries.Methods and analysisDIET-HD will recruit approximately 10 000 adults who have ESKD treated by clinics administered by a single dialysis provider in Argentina, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden and Turkey. Recruitment will take place between March 2014 and June 2015. The study has currently recruited 8000 participants who have completed baseline data. Nutritional intake and dietary patterns will be measured using the Global Allergy and Asthma European Network (GA2LEN) food frequency questionnaire. The primary dietary exposures will be n-3 and n-6 polyunsaturated fatty acid consumption. The primary outcome will be cardiovascular mortality and secondary outcomes will be all-cause mortality, infection-related mortality and hospitalisation.Ethics and disseminationThe study is approved by the relevant Ethics Committees in participating countries. All participants will provide written informed consent and be free to withdraw their data at any time. The findings of the study will be disseminated through peer-reviewed journals, conference presentations and to participants via regular newsletters. We expect that the DIET-HD study will inform large pragmatic trials of nutrition or dietary interventions in the setting of advanced kidney disease.
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