Hypertonicity counteracts MCL 1 and renders BCL XL a synthetic lethal target in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is an aggressive and difficult‐to‐treat cancer entity. Current therapies ultimately aim to activate the mitochondria‐controlled (intrinsic) apoptosis pathway, but complex alterations in intracellular signaling cascades and the extracellular microenvironment hamper treatment response. On the one hand, proteins of the BCL‐2 family set the threshold for cell death induction and prevent accidental cellular suicide. On the other hand, controlling a cell's readiness to die also determines whether malignant cells are sensitive or resistant to anticancer treatments. Here, we show that HNSCC cells upregulate the proapoptotic BH3‐only protein NOXA in response to hyperosmotic stress. Induction of NOXA is sufficient to counteract the antiapoptotic properties of MCL‐1 and switches HNSCC cells from dual BCL‐XL/MCL‐1 protection to exclusive BCL‐XL addiction. Hypertonicity‐induced functional loss of MCL‐1 renders BCL‐XL a synthetically lethal target in HNSCC, and inhibition of BCL‐XL efficiently kills HNSCC cells that poorly respond to conventional therapies. We identify hypertonicity‐induced upregulation of NOXA as link between osmotic pressure in the tumor environment and mitochondrial priming, which could perspectively be exploited to boost efficacy of anticancer drugs

Benzodiazepine use in Santiago, Chile.

INTRODUCTION: To describe benzodiazepine use in the adult population from Santiago, Chile and attempt to establish associations with different sociodemographic and medical variables. METHODS: This is a cross-sectional study whose sampling frame was the adult population, aged 16 to 64 years (n = 3,237,286). The sampling strategy was probabilistic, poly-stage and stratified. RESULTS: A total of 3,870 persons were interviewed. Prevalence of benzodiazepine use was 3.84 %. Statistically significant associations were found between benzodiazepine use and gender, age, marital status, income, presence of a common mental disorder and health perception. DISCUSSION: Training of the general practitioner to regulate the use of benzodiazepine is necessary

Sleep disorders in the adult population of Santiago of Chile and its association with common psychiatric disorders Trastornos del sueño en la población adulta de Santiago de Chile y su asoeiación eon trastornos psiquiátricos eomunes

Introduction: Sleep disorders are a frequent problem and they are a usual reason of primary care consultation, because they are associated to significant deterioration in quality of life. Insomnia is the most common sleep disorder whose estimated total prevalence in adults is 19.1%, 85% of which are chronic insomnia. This, in turn, is closely related to psychiatric disorders and has been described as a depressive episode marker. Aims: To characterize the Santiago adult population suffering from sleep disorders and analyze their statistical association with common mental disorders. Methodology: It corresponds to a secondary analysis of the survey "Common Mental Disorders in Santiago." A cross-sectional survey that used the adult population of Santiago whose ages ranged from 16 to 64 years as a sample was carried out. A structured interview covering sociodemographic factors and the Revised Clinical Interview Schedule (CIS-R) to measure emotional symptoms were applied. Results: 3867 peop

Intimate partner violence in older women in Spain: prevalence, health consequences, and service utilization

The purpose of this study is to estimate the prevalence of lifetime intimate partner violence (IPV) in older women and to analyze its effect on women's health and Healthcare Services utilization. Women aged 55 years and over (1,676) randomly sampled from Primary Healthcare Services around Spain were included. Lifetime IPV prevalence, types, and duration were calculated. Descriptive and multivariate procedures using logistic and multiple lineal regression models were used. Of the women studied, 29.4% experienced IPV with an average duration of 21 years. Regardless of the type of IPV experienced, abused women showed significantly poorer health and higher healthcare services utilization compared to women who had never been abused. The high prevalence detected long standing duration, negative health impact, and high healthcare services utilization, calling attention to a need for increased efforts aimed at addressing IPV in older women