Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces

The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded ‘amoeboid-like’ mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar ‘mesenchymal-like’ mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.     

Nutritional Surveillance of Christian Orthodox Minority Adolescents in Istanbul

Previous studies have shown that the diets of migrant populations are of poor quality; however, studies on populations remaining in one geographical region as a minority after an acute population movement are scarce. Therefore, the aim of the present study was to assess dietary intake and growth of Greek minority adolescents in Turkey. Anthropometric measurements and dietary assessment were performed in 103 Greek Orthodox students (aged 10–19 years old) of three minority schools in Istanbul. Prevalence of overweight and obesity according to the WHO growth charts was 39.8 %. Accordingly, 40 % of the sample exhibited excess body fat. Dietary intakes of protein, carbohydrate, fiber, vitamins E and D, folic acid and calcium were inadequate, while energy, total fat and iron intakes were considered adequate. Our results indicate that Greek minority adolescents living in Turkey have similar weight status compared to their counterparts in Greece, but greater body fat than Turkish coevals, while being at risk of several nutrient inadequacies.     

Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer's Disease

The lack of an adequate therapy for Alzheimer''s Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm “Multi-Target-Directed Ligands” (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches.     

The Relationship Between Social Support,HIV Serostatus,and Perceived Likelihood of Being HIV Positive Among Self-Settled Female,Foreign Migrants in Cape Town,South Africa

Female cross-border migrants experience elevated risks for HIV, and migrants in South Africa may face additional risks due to the country’s underlying HIV prevalence. These risks may be mitigated by the receipt of social support. A behavioral risk-factor survey was administered using respondent-driven sampling. Multivariable regression models assessed the relationships between social support and two HIV outcomes: HIV serostatus and perceived HIV status. Low social support was not significantly associated with HIV status (aOR?=?1.03, 95?% CI 0.43–2.46), but was significantly related to a perception of being HIV positive (aPR?=?1.36, 95?% CI 1.04–1.78). Age, marital status, and education level were significantly associated with HIV serostatus. Illegal border-crossing, length of time in South Africa, anal sex, and transactional sex were significantly associated with aperception of being HIV positive. Future research should investigate how HIV risks and the receipt of social support change throughout the migration process.     

Fibromyalgia Pathogenesis and Treatment Options Update

This review article presents and summarizes up-to-date literature on the clinical manifestations, diagnosis, pathophysiological mechanisms, and treatment options for fibromyalgia patients. First, the most recent diagnostic criteria for fibromyalgia, as put forth by the American College of Rheumatology will be summarized. Clinical features, including chronic widespread pain, hyperalgesia, mood disorders, anxiety, and disturbed sleep patterns will be explored in-depth. The pathogenesis and pathophysiology of fibromyalgia involves alterations in multiple ascending and descending central nervous system pathways, as well as peripheral pathways, leading to heightened pain sensitivity. Risk factors have been studied extensively, and the most recent research focuses on various genetic influences and the contributions of stress and poor sleep. Lastly, the discussion in this article focuses on treatment options for fibromyalgia; some have been mainstay options for many years. Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin reuptake inhibitors, norepinephrine/serotonin reuptake inhibitors, as well as some investigational agents. The evidence behind non-pharmacologic treatments, including massage therapy, exercise, and acupuncture, are discussed.     

Targeting the Human Cerebellum with Transcranial Direct Current Stimulation to Modulate Behavior: a Meta-Analysis

Transcranial direct current stimulation (tDCS) is increasingly used to study motor- and non-motor-related functions of the cerebellum. The aim of the present study was to quantitatively review available studies to estimate the efficacy of cerebellar tDCS in altering motor- and cognitive-related behavioral performance in healthy volunteers. The present meta-analysis included 32 sham-controlled studies. Results from random effects modeling of the cumulative effect size demonstrated that anodal and cathodal tDCS to the cerebellum were effective in changing performance. No evidence for polarity-dependent effects of cerebellar tDCS was found. Current findings establish the feasibility to target motor and non-motor-related cerebellar functions with tDCS, but arguably due to anatomical differences between the cerebellum and cerebral cortex, the polarity of tDCS is not predictive of the direction of the behavioral changes in healthy volunteers.