Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events

Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis. Perturbing positive feedback gave rise to a sluggish, variable entry and progression through mitosis and uncoupled duration of mitosis from variability in cell cycle length. We show that positive feedback is important to keep mitosis short, constant, and temporally insulated and anticipate it might be a commonly used regulatory strategy to create modularity in other biological systems

Interventions to prevent urinary catheter-associated infections in children and neonates: a systematic review.

INTRODUCTION: Few data are available to inform strategies for the prevention of catheter-associated urinary tract infection (CAUTI) in children and neonates. Many recommendations are derived from studies in adults and cannot be applied to the paediatric population. OBJECTIVE: This study was aimed to identify all studies that measured the efficacy of an intervention for the prevention of CAUTI in children and neonates. METHODS: A systematic review using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) was conducted. Eligible studies published between January 1st, 1995 and December 31st, 2017, were identified in PubMed, the Cochrane Database of Systematic Reviews, LILACS, SciELO and DOAJ if applying an intervention with the aim of CAUTI prevention in inpatient children, infants or neonates. The following study designs were included: controlled and non-controlled before-and-after studies, (controlled) interrupted time series analyses and randomized controlled trials. Quantitative or qualitative studies on interventions in both adults and children were eligible if data on children could be extracted. Reviews, case series, letters, notes, conference abstracts and opinion articles were excluded. RESULTS: Of 99 articles identified, six were included in the final analysis, after consensus from three independent investigators. Four studies used a multimodal strategy (using at least four or more different components at the same time) as follows: aseptic rules during catheter insertion and removal; cleaning the urethral meatus with sterile water; use of a new silicone catheter per insertion with a closed sterile drainage system by a sterile technique; daily evaluation of catheter requirement; placement of indwelling urinary catheters only for approved indications; reducing of urinary catheter days and positioning of the patient and collection device to assist in urine drainage. One study tested periurethral cleaning intervention to reduce CAUTI. One study described the association of the presence of a physician safety champion with urinary catheter device utilization ratios. Catheter-associated UTI reduction rates were reported in four studies; three achieved statistically significant decreases in CAUTI rates. Positive results were achieved only when a multimodal strategy was used with at least four or more components. This strategy could be adopted for paediatric healthcare institutions to reduce CAUTI rates in children and neonates. CONCLUSION: Evidence exists to support the use of a multimodal strategy for CAUTI reduction in hospitalized children and neonates

Metabolic responses to acute physical exercise in young rats recovered from fetal protein malnutrition with a fructose-rich diet

<p>Abstract</p> <p>Background</p> <p>Malnutrition <it>in utero </it>can "program" the fetal tissues, making them more vulnerable to metabolic disturbances. Also there is association between excessive consumption of fructose and the development of metabolic syndrome. However, there is little information regarding the acute effect of physical exercise on subjects recovered from malnutrition and/or fed with a fructose-rich diet. The objective of this study was to evaluate the metabolic aspects and the response to acute physical exercise in rats recovered from fetal protein malnutrition with a fructose-rich diet.</p> <p>Methods</p> <p>Pregnant Wistar rats were fed with a balanced (B) diet or a low-protein (L) diet. After birth and until 60 days of age, the offspring were distributed into four groups according to the diet received: B: B diet during the whole experiment; balanced/fructose (BF): B diet until birth and fructose-rich (F) diet afterwards; low protein/balanced (LB): L diet until birth and B diet afterwards; low protein/fructose (LF): L diet until birth and F diet afterwards.</p> <p>Results</p> <p>The excess fructose intake reduced the body weight gain, especially in the BF group. Furthermore, the serum total cholesterol and the LDL cholesterol were elevated in this group. In the LF group, the serum total cholesterol and the muscle glycogen increased. Acute physical exercise increased the serum concentrations of glucose, triglycerides, HDL cholesterol and liver lipids and reduced the concentrations of muscle glycogen in all groups.</p> <p>Conclusion</p> <p>An excess fructose intake induced some signs of metabolic syndrome. However, protein malnutrition appeared to protect against the short term effects of fructose. In other hand, most responses to acute physical exercise were not influenced by early malnutrition and/or by the fructose overload.</p

Cognitive decline in patients with prostate cancer: study protocol of a prospective cohort, NEON-PC

Introduction: Prostate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline. Methods: Participants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants' cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist. Ethics and dissemination: The study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education) under the project ‘NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017), and the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT) financed by national funds from FCT. SM was funded under the scope of the project ‘NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). Individual PhD grants attributed to ARC (SFRH/BD/102181/2014) and NA (SFRH/BD/119390/2016) were funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE)

Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

Interventions to prevent neonatal healthcare-associated infections in low-resource settings: a systematic review

Background: Clinically suspected and laboratory-confirmed bloodstream infections are frequent causes of morbidity and mortality during neonatal care. The most effective infection prevention and control (IPC) interventions for neonates in low-and-middle-income countries (LMIC) are unknown. Aim: To identify effective interventions in the prevention of hospital-acquired bloodstream infections in LMIC neonatal units. Methods: Medline, PUBMED, The Cochrane Database of Systematic Reviews, EMBASE, and PsychInfo (January 2003 – October 2020) were searched to identify studies reporting single or bundled interventions for prevention of bloodstream infections in LMIC neonatal units. Results: Our initial search identified 5206 articles; following application of filters, 27 publications met the inclusion and ICROMS assessment criteria and were summarised in the final analysis. No studies were carried out in low-income countries, only one in sub-Saharan Africa and just two in multiple countries. Of the 18 single intervention studies, most targeted skin (n=4) and gastrointestinal mucosal integrity (n=5). Whereas emollient therapy and lactoferrin achieved significant reductions in proven neonatal infection, glutamine and mixed probiotics showed no benefit. Chlorhexidine gluconate for cord care and kangaroo mother care reduced infection in individual single-centre studies. Of the nine studies evaluating bundles, most focused on prevention of device-associated infections and achieved significant reductions in catheter- and ventilator-associated infections. Conclusion: There is a limited evidence-base for the effectiveness of IPC interventions in LMIC neonatal units; bundled interventions targeting device-associated infections were most effective. More multi-site studies with robust study designs are needed to inform IPC intervention strategies in low-resource neonatal units

A pivotal role for starch in the reconfiguration of 14C-partitioning and allocation in Arabidopsis thaliana under short-term abiotic stress.

Plant carbon status is optimized for normal growth but is affected by abiotic stress. Here, we used 14C-labeling to provide the first holistic picture of carbon use changes during short-term osmotic, salinity, and cold stress in Arabidopsis thaliana. This could inform on the early mechanisms plants use to survive adverse environment, which is important for efficient agricultural production. We found that carbon allocation from source to sinks, and partitioning into major metabolite pools in the source leaf, sink leaves and roots showed both conserved and divergent responses to the stresses examined. Carbohydrates changed under all abiotic stresses applied; plants re-partitioned 14C to maintain sugar levels under stress, primarily by reducing 14C into the storage compounds in the source leaf, and decreasing 14C into the pools used for growth processes in the roots. Salinity and cold increased 14C-flux into protein, but as the stress progressed, protein degradation increased to produce amino acids, presumably for osmoprotection. Our work also emphasized that stress regulated the carbon channeled into starch, and its metabolic turnover. These stress-induced changes in starch metabolism and sugar export in the source were partly accompanied by transcriptional alteration in the T6P/SnRK1 regulatory pathway that are normally activated by carbon starvation