Oligophrenin-1: the link between calcium-regulated exocytosis and compensatory endocytosis in neuroendocrine cells

In neuroendocrine cells, hormones and neuropeptides are released from large-dense core vesicles (secretory granules) by calcium-regulated exocytosis. Following exocytosis, compensatory uptake of membrane is required to maintain membrane homeostasis and allow recycling of secretory vesicle membranes. How these cells initiate and regulate this compensatory endocytosis remains poorly understood. Our recent data suggests that oligophrenin-1 (OPHN1) is a link coupling calcium-regulated exocytosis to compensatory endocytosis of secretory granules in the adrenal chromaffin cells (Houy et al., 2015, J Neurosci. 2015, 35:11045-55). Here, we highlight the major evidence and discuss how OPHN1 could couple these two processes

Searching for maintenance in exercise interventions for cancer survivors

Translating evidence-based exercise interventions into practice is important for expanding the capacity to support cancer survivors. Using the reach, efficacy/effectiveness, adoption, implementation, and maintenance (RE-AIM) framework and scoping study methodology, we addressed the research question, “What is known about the maintenance of exercise interventions for cancer survivors that would inform translation from research to practice and community settings?” Maintenance was investigated at the individual and setting level

Gene expression signature discriminates sporadic from post-radiotherapy-induced thyroid tumors

Both external and internal exposure to ionizing radiation are strong risk factors for the development of thyroid tumors. Until now, the diagnosis of radiation-induced thyroid tumors has been deduced from a network of arguments taken together with the individual history of radiation exposure. Neither the histological features nor the genetic alterations observed in these tumors have been shown to be specific fingerprints of an exposure to radiation. The aim of our work is to define ionizing radiation-related molecular specificities in a series of secondary thyroid tumors developed in the radiation field of patients treated by radiotherapy. To identify molecular markers that could represent a radiation-induction signature, we compared 25K microarray transcriptome profiles of a learning set of 28 thyroid tumors, which comprised 14 follicular thyroid adenomas (FTA) and 14 papillary thyroid carcinomas (PTC), either sporadic or consecutive to external radiotherapy in childhood. We identified a signature composed of 322 genes which discriminates radiation-induced tumors (FTA and PTC) from their sporadic counterparts. The robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 29 tumors (16 FTA and 13 PTC). After the histology code break by the clinicians, 26/29 tumors were well classified regarding tumor etiology, 1 was undetermined, and 2 were misclassified. Our results help shed light on radiation-induced thyroid carcinogenesis, since specific molecular pathways are deregulated in radiation-induced tumors

The impact of behavioral and mental health risk assessments on goal setting in primary care

Patient-centered health risk assessments (HRAs) that screen for unhealthy behaviors, prioritize concerns, and provide feedback may improve counseling, goal setting, and health. To evaluate the effectiveness of routinely administering a patient-centered HRA, My Own Health Report, for diet, exercise, smoking, alcohol, drug use, stress, depression, anxiety, and sleep, 18 primary care practices were randomized to ask patients to complete My Own Health Report (MOHR) before an office visit (intervention) or continue usual care (control). Intervention practice patients were more likely than control practice patients to be asked about each of eight risks (range of differences 5.3-15.8 %, p < 0.001), set goals for six risks (range of differences 3.8-16.6 %, p < 0.01), and improve five risks (range of differences 5.4-13.6 %, p < 0.01). Compared to controls, intervention patients felt clinicians cared more for them and showed more interest in their concerns. Patient-centered health risk assessments improve screening and goal setting.Trial RegistrationClinicaltrials.gov identifier: NCT01825746

CRH – Centre de recherches historiques

Hinnerk Bruhns, directeur de recherche au CNRSCatherine Colliot-Thélène, professeur à l’Université Rennes-IPatrice Duran, professeur à l’ENS-Cachan Autour de Max Weber Au cours de l’année ont été abordées, dans différents domaines des sciences sociales, des questions relevant des œuvres de Max Weber et de ses contemporains, ainsi que de leur postérité au cours du vingtième siècle. Le séminaire s’est ouvert le 16 novembre 2010 par une conférence de Monsieur Ulrich Bielefeld, directeur de l’uni..

Frailty Intervention Trial (FIT)

<p>Abstract</p> <p>Background</p> <p>Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity). Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty.</p> <p>We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people.</p> <p>Methods and Design</p> <p>A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period.</p> <p>Discussion</p> <p>This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a new approach to the treatment of older people at risk of further functional decline and institutionalisation. The strategies to be examined are readily transferable to routine clinical practice and are applicable broadly in the setting of aged care health services.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trails Registry: ACTRN12608000250336.</p

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake