Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma

Standardised description of health and social care: A systematic review of use of the ESMS/DESDE (European Service Mapping Schedule/Description and Evaluation of Services and DirectoriEs)

Background: Evidence-informed planning and interpretation of research results both require standardised description of local care delivery context. Such context analysis descriptions should be comparable across regions and countries to allow benchmarking and organizational learning, and for research findings to be interpreted in context. The European Service Mapping Schedule (ESMS) is a classification of adult mental health services that was later adapted for the assessment of health and social systems research (Description and Evaluation of Services and DirectoriEs - DESDE). The aim of the study was to review the diffusion and use of the ESMS/DESDE system in health and social care and its impact in health policy and decision-making. Method: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (1997–2018). Results: Out of 155 papers mentioning ESMS/DESDE, 71 have used it for service research and planning. The classification has been translated into eight languages and has been used by seven international research networks. Since 2000, it has originated 11 instruments for health system research with extensive analysis of their metric properties. The ESMS/DESDE coding system has been used in 585 catchment areas in 34 countries for description of services delivery at local, regional and national levels. Conclusions: The ESMS/DESDE system provides a common terminology, a classification of care services, and a set of tools allowing a variety of aims to be addressed in healthcare and health systems research. It facilitates comparisons across and within countries for evidence-informed planning

Regional controls on holocene sedminentation patterns along the Peru contonental margin; long term implications for El Niño-Southern Oscillation

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The impact of a change on the size of the smoke compartment in the evacuation of health care facilities

Evacuation in health-care facilities is complex due to the physical impairment of the patients. This kind of evacuation usually requires the assistance of the workforce members. A proposed change of NFPA 101, Life Safety Code, would increase the maximum allowable size of a smoke compartment (a space within the building enclosed by smoke barriers on all sides that restricts the movement of smoke) in health-care occupancies from 2090 m2 to 3700 m2, almost double the size. This study aims to analyse the impact of this change in the required time for evacuating patients during a fire in order to understand the consequences of that potential change. This paper is focused on the area where the patient?s rooms are located. The evacuation scenario is a floor plan comprised of four smoke compartments. To analyse the proposed change, the smoke barriers between two adjacent compartments were removed in a floor plan and three ratios of number of patients per one staff member were considered (4:1, 3:1 and 2:1). A computational methodology was conducted to calibrate the model STEPS for simulating assisted evacuation processes. In addition, Fire Dynamic Simulator (FDS) was used to simulate the fire and smoke spread in a table and a PC to compare fire and evacuation results The evacuation results show that the change of the smoke compartment size increases the mean evacuation time by 23%; however, the fire results show that the available safe egress time is 16 min for both smaller and large smoke compartment. The ratio of the number of patients per staff member is also a strong factor that increases the evacuation up to 82% when comparing the ratios of 2 patients per staff member and 4 patients per staff member

Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration: ClinicalTrials.gov NCT0200571

Predicting the onset and persistence of episodes of depression in primary health care. The predictD-Spain study: Methodology

Background: The effects of putative risk factors on the onset and/or persistence of depression remain unclear. We aim to develop comprehensive models to predict the onset and persistence of episodes of depression in primary care. Here we explain the general methodology of the predictD-Spain study and evaluate the reliability of the questionnaires used. Methods: This is a prospective cohort study. A systematic random sample of general practice attendees aged 18 to 75 has been recruited in seven Spanish provinces. Depression is being measured with the CIDI at baseline, and at 6, 12, 24 and 36 months. A set of individual, environmental, genetic, professional and organizational risk factors are to be assessed at each follow-up point. In a separate reliability study, a proportional random sample of 401 participants completed the test-retest (251 researcher-administered and 150 self-administered) between October 2005 and February 2006. We have also checked 118,398 items for data entry from a random sample of 480 patients stratified by province. Results: All items and questionnaires had good test-retest reliability for both methods of administration, except for the use of recreational drugs over the previous six months. Cronbach's alphas were good and their factorial analyses coherent for the three scales evaluated (social support from family and friends, dissatisfaction with paid work, and dissatisfaction with unpaid work). There were 191 (0.16%) data entry errors. Conclusion: The items and questionnaires were reliable and data quality control was excellent. When we eventually obtain our risk index for the onset and persistence of depression, we will be able to determine the individual risk of each patient evaluated in primary health car

Kanamycin uptake into Escherichia coli is facilitated by OmpF and OmpC porin channels located in the outer membrane

Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of Escherichia coli. Our analysis revealed that, despite its relatively large size, about 10–20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 μM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a defined set of E. coli porin mutants provide evidence that translocation of kanamycin via porins is relevant for antibiotic potency. The values are discussed with respect to other antibiotics