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Apoptosis and necroptosis are major forms of regulated cell death (10). Necroptosis involves in part molecules also found to regulate apoptosis but depends on the formation of the necrosome, consisting [...], Metastasis is the leading cause of cancer-related death in humans. It is a complex multistep process during which individual tumour cells spread primarily through the circulatory system to colonize distant organs (1-3). Once in the circulation, tumour cells remain vulnerable, and their metastatic potential largely depends on a rapid and efficient way to escape from the blood stream by passing the endothelial barrier (4-9). Evidence has been provided that tumour cell extravasation resembles leukocyte transendothelial migration (7-9). However, it remains unclear how tumour cells interact with endothelial cells during extravasation and how these processes are regulated on a molecular level. Here we show that human and murine tumour cells induce programmed necrosis (necroptosis) of endothelial cells, which promotes tumour cell extravasation and metastasis. Treatment of mice with the receptor-interacting serine/threonineprotein kinase 1 (RIPKl)-inhibitor necrostatin-1 or endothelial-cell-specific deletion of RIPK3 reduced tumour-cell-induced endothelial necroptosis, tumour cell extravasation and metastasis. In contrast, pharmacological caspase inhibition or endothelial-cell-specific loss of caspase-8 promoted these processes. We furthermore show in vitro and in vivo that tumour-cell-induced endothelial necroptosis leading to extravasation and metastasis requires amyloid precursor protein expressed by tumour cells and its receptor, death receptor 6 (DR6), on endothelial cells as the primary mediators of these effects. Our data identify a new mechanism underlying tumour cell extravasation and metastasis, and suggest endothelial DR6-mediated necroptotic signalling pathways as targets for anti-metastatic therapies.

Rates of alcohol use and alcohol use disorder (AUD) vary with geographic location. Research on risks for AUD associated with living in a rural versus urban setting is complicated by [...]

Alcohol use and misuse account for 3.3 million deaths every year, or 6 percent of all deaths worldwide. The harmful effects of alcohol misuse are far reaching and range from [...]

Introduction Maternal smoking during pregnancy is a serious and preventable risk factor that is associated with poor pregnancy outcomes. In the United States, measures of both infant morbidity and mortality [...], Poor pregnancy and birth outcomes are major problems in the United States, and maternal smoking during pregnancy has been identified as one of the most preventable risk factors associated with these outcomes. This study examines less explored risk factors of smoking among underserved African American pregnant women. A cross-sectional survey was conducted at an outpatient obstetrics-gynecology clinic of an inner-city university hospital in Virginia from March 2009 through January 2011 in which pregnant women (N = 902) were interviewed at their first prenatal care visit. Survey questions included items related to women's sociodemographic characteristics as well as their pregnancy history; criminal history; receipt of social services; child protective services involvement; insurance status; and history of substance abuse, domestic violence, and depression. Multiple logistic regression was conducted to calculate odds ratios and 95% confidence intervals depicting the relationship between these factors and smoking during pregnancy. The analysis reported that maternal age [OR = 1.08, 95% CI = 1.05-1.12], less than high school education [OR = 4.30, 95% CI = 2.27-8.14], unemployed [OR = 2.33, 95% CI = 1.35-4.04], criminal history [OR = 1.66, 95% CI = 1.05-2.63], receipt of social services [OR = 2.26, 95% CI = 1.35-3.79] alcohol use [OR = 2.73, 95% CI = 1.65-4.51] and illicit drug use [OR = 1.97, 95% CI = 1.044-3.74] during pregnancy were statistically significant risk factors associated with smoking during pregnancy. In addition to the well known risk factors, public health professionals should be aware that criminal history and receipt of social services are important factors associated with smoking during pregnancy. Social service providers such as WIC and prisons and jails may offer a unique opportunity for education and cessation interventions during the preconception or interconception period. Keywords Smoking during pregnancy * Correlates of smoking * Criminal history * Social services * Preconception health

Social work's person-in-environment perspective requires that practitioners consider the social and physical environment--its problems, supports, and opportunities--and, specifically, individuals' goodness of fit with it. Yet the development of models for [...], This article reviews recent theory and research on geographic disparities in mental health and their implications for social work. It focuses on work emerging from the fields of mental health geography, psychiatric epidemiology, and social work, arguing that a wide range of spatial disparities in mental health are important to understand but that of greatest relevance are inequities, or disparities, that violate fundamental norms of fairness and social justice. Research is reviewed on geographic variations in subjective well-being and mental health, on personality (using the five-factor model), and on psychopathology as well as several studies on the disparate implementation of mental health policy and services. Critical is the need to simultaneously assess, on the one hand, differential patterns of mental health conditions and, on the other, the services and policies designed to address them-the fact that considering only one dimension often leads to unintended consequences. Many of the most outstanding disparities have been found to exist at the local level, between towns and neighborhoods, and are based on socioeconomic conditions. This review concludes by discussing the implications of geographic disparities in mental health for allocation decisions and for social work practice, including decisions about the most efficacious mix of services at both the community and clinical practice levels. KEY WORDS: geography of mental health; health disparities; quality of life; spatiality; subjective well-being

Introduction Non-small cell lung cancer (NSCLC) is a major health problem worldwide (Alberg and Samet 2003). Surgery is the only potential curative treatment, despite the fact that most patients undergoing [...], Non-small cell lung cancer (NSCLC) is a major health problem. Surgery is the only potential curative treatment, in spite of the high recurrence and mortality rates. Low molecular weight heparins (LMWH) have been suggested to have a positive impact on the outcome of various cancers, mainly attributed to their anticoagulant properties; yet a direct antineoplastic effect has not been excluded. We thought to evaluate the direct effect of the LMWH enoxaparin on the human lung adenocarcinomic epithelial cell line A549 and to determine potential antiproliferative and antimetastatic effects that could guide future trials. A549 cells were cultured with different concentrations of enoxaparin (1-30 U/mL). Cell counting was performed at 24, 48, and 72 h. Detection of c-Myc protein and CD44 protein was performed by electrophoresis and Western blotting. Statistical analysis was performed using paired Student's t tests. Cell counts were decreased with increasing concentrations and time of exposure to enoxaparin. This corresponds to decreased expression of c-Myc and CD44. In conclusion, enoxaparin displayed a direct dose and exposure duration dependent suppressor effect on A549 cell proliferation and the expression of both c-Myc and CD44 in vitro, suggesting reduced proliferative and metastatic potentials of these cells. Key words: CD44, c-Myc, low molecular weight heparins, non-small cell lung cancer, A549 cell line, pulmonary adenocarcinoma, lung cancer. Le cancer du poumon non a petites cellules (CPNPC) constitue un probleme de sante majeur. La chirurgie est le seul traitement curatif possible, malgre les hauts taux de recurrence et de mortalite. Les heparines de bas poids moleculaire (HBPM) pourraient avoir un impact sur revolution de divers cancers, en raison principalement de leurs proprietes anticoagulantes, bien qu'on ne puisse exclure un effet direct antineoplasique. Nous avons eu pour objectif d'evaluer l'effet direct de l'HBPM enoxaparine sur la lignee de cellules A549 issues d'adenocarcinomes de poumon humain et de determiner les effets antiproliferatifs et antimetastatiques qui pourraient guider les futures etudes. Nous avons cultive les cellules A549 avec differentes concentrations d'enoxaparine (1-30 U/mL), et effectue la numerotation des cellules a 24, 48 et 72 h. Nous avons detecte les proteines c-Myc et CD44 par electrophorese et transfert Western, et realise l'analyse statistique par un test t pour echantillons apparies. Les numerotations des cellules ont diminue avec l' augmentation des concentrations et du temps d' exposition a l'enoxaparine, ceci allant de pair avec la diminution de l'expression de c-Myc et CD44. Ainsi, l'enoxaparine a un effet suppresseur dependant de la dose et de la duree d'exposition sur la proliferation des cellules A549 et l'expression de c-Myc et de CD44 in vitro, ce qui autorise a penser a une diminution des potentiels proliferatif et metastatique de ces cellules. Mots-cles : CD44, c-Myc, heparines de bas poids moleculaire, cancer du poumon non a petites cellules, lignee cellulaire A549, adenocarcinome bronchique, cancer du poumon. [Traduit par la Redaction]

In addition to increasing beverage taxes or prices as a means to reduce alcohol accessibility, policymakers also may limit alcohol availability through laws and regulations that (1) proscribe sales to [...]

It has been widely recognized that an epidemiological study limited to individual risk factors will not be adequate to address the current public health challenges of human immunodeficiency virus (HIV)/acquired [...]

Adolescents are facing a growing array of socioemotional and mental health issues. Marsh (2004) notes, for instance, that approximately 4.5 to 6.3 million children and adolescents in the United States [...], Approximately 4.5 to 6.3 million youth experience serious emotional disturbances. Unfortunately, many of them have unmet mental health needs. Tools used in personality assessment can offer unparalleled assistance in diagnosis, and assist in designing appropriate interventions. Unfortunately, not all psychologists embrace personality assessment as a key component in conducting a comprehensive psychological evaluation. In this article the effective use of personality assessment tools is described, with particular attention to issues of comorbidity. Guidelines for effective practice are also offered.

During the past few decades, social gerontologists have debated the compression of morbidity thesis (Quadagno, 2002). This debate was initiated in 1980 by James Fries, a physician teaching at Stanford [...]

Hypertensive disease can lead to cardiac hypertrophy and heart failure and is a major cause of death in developed countries. The heart failure that follows prolonged hypertension is characterized by [...], Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes taken from hypertensive rats (Dahl SS/Jr) and SH-HF rats in heart failure. Confocal microscopy and patch-clamp methods were used to examine excitation-contraction (EC) coupling, and the relation between the plasma membrane calcium current ([I.sub.Ca]) and evoked calcium release from the sarcoplasmic reticulum (SR), which was visualized as 'calcium sparks.' The ability of [I.sub.Ca] to trigger calcium release from the SR in both hypertrophied and failing hearts was reduced. Because [I.sub.Ca] density and SR calcium-release channels were normal, the defect appears to reside in a change in the relation between SR calcium-release channels and sarcolemmal calcium channels. Β-adrenergic stimulation largely overcame the defect in hypertrophic but not failing heart cells. Thus, the same defect in EC coupling that develops during hypertrophy may contribute to heart failure when compensatory mechanisms fail.

1. Introduction Peroxisome proliferator-activated receptor gamma (PPARG) gene is a member of nuclear hormone receptor superfamily, and it regulates the transcription of several genes involved in glucose metabolism, adipocyte differentiation, [...], Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes--particularly diabetic women with the proliferative retinopathy--were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not. Copyright [C] 2009 Valerio Costa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How do you get a perfect sphere to acquire a front and back, right-hand and left-hand sides? Such is the challenge addressed during oogenesis, when the molecular signals that initiate [...]