Abundance and Diversity of Holothuroids in Shallow Habitats of the Northern Red Sea

Holothuroid sea cucumbers are vital members of Coral Reefs and associated marine habitats and provide vital ecological services. In the southern regions of the Red Sea their populations have been decimated by overfishing. The main objective of this study was to test the hypothesis that the northern part of the Red Sea serves as an ecological refuge for the species threatened farther to the south. Accordingly, populations of sea cucumbers in 4 shallow sites south of Eilat, Israel (29°33′00N 34°57′14E), were repeatedly surveyed from November 2013 to April 2014. Overall 11 species were observed in these shallow sites. Their abundance and diversity differed significantly between sites, but not temporally. In sites in marine protected areas, with an intact fringing reef, diversity was high, with Holothuria edulis and Bohadschia sp. being the most common species. In areas with higher human use and characterized by rubble and scattered corals, diversity was low, and Actinopyga bannwarthi was the most common species. The observed abundance and diversity did not support the refuge hypothesis. These findings are discussed in relation to other surveys of abundance and diversity in similar habitats

Abundance and Diversity of Holothuroids in Shallow Habitats of the Northern Red Sea

Holothuroid sea cucumbers are vital members of Coral Reefs and associated marine habitats and provide vital ecological services. In the southern regions of the Red Sea their populations have been decimated by overfishing. The main objective of this study was to test the hypothesis that the northern part of the Red Sea serves as an ecological refuge for the species threatened farther to the south. Accordingly, populations of sea cucumbers in 4 shallow sites south of Eilat, Israel (29 ∘ 33 00N 34 ∘ 57 14E), were repeatedly surveyed from November 2013 to April 2014. Overall 11 species were observed in these shallow sites. Their abundance and diversity differed significantly between sites, but not temporally. In sites in marine protected areas, with an intact fringing reef, diversity was high, with Holothuria edulis and Bohadschia sp. being the most common species. In areas with higher human use and characterized by rubble and scattered corals, diversity was low, and Actinopyga bannwarthi was the most common species. The observed abundance and diversity did not support the refuge hypothesis. These findings are discussed in relation to other surveys of abundance and diversity in similar habitats

Dose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach

International audienceIt has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro. A first set of mathematical models, based on basic principles of pharmacokinetics/pharmacodynamics, did not appropriately describe the dose-dependence and duration of the host response regarding the effects on invasion. We therefore provide an alternative mathematical model with a dose-dependent threshold, instead of a concentration-dependent one, that describes better the data. This model is integrated into a global model defining all three host-mediated effects. It not only precisely describes the data, but also correctly predicts host-mediated effects at different doses as well as the duration of the host response. This mathematical model may serve as a tool to predict the host response to chemotherapy in cancer patients, and therefore may be used to design chemotherapy regimens with improved therapeutic outcome by minimizing host mediated effects

Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1

Radiotherapy induces immune-related responses in cancer patients by various mechanisms. Here, we investigate the immunomodulatory role of tumor-derived microparticles (TMPs)-extracellular vesicles shed from tumor cells-following radiotherapy. We demonstrate that breast carcinoma cells exposed to radiation shed TMPs containing elevated levels of immune-modulating proteins, one of which is programmed death-ligand 1 (PD-L1). These TMPs inhibit cytotoxic T lymphocyte (CTL) activity both in vitro and in vivo, and thus promote tumor growth. Evidently, adoptive transfer of CTLs pre-cultured with TMPs from irradiated breast carcinoma cells increases tumor growth rates in mice recipients in comparison with control mice receiving CTLs pre-cultured with TMPs from untreated tumor cells. In addition, blocking the PD-1-PD-L1 axis, either genetically or pharmacologically, partially alleviates TMP-mediated inhibition of CTL activity, suggesting that the immunomodulatory effects of TMPs in response to radiotherapy is mediated, in part, by PD-L1. Overall, our findings provide mechanistic insights into the tumor immune surveillance state in response to radiotherapy and suggest a therapeutic synergy between radiotherapy and immune checkpoint inhibitors

Macrophage-Induced Lymphangiogenesis and Metastasis following Paclitaxel Chemotherapy Is Regulated by VEGFR3

While chemotherapy strongly restricts or reverses tumor growth, the response of host tissue to therapy can counteract its anti-tumor activity by promoting tumor re-growth and/or metastases, thus limiting therapeutic efficacy. Here, we show that vascular endothelial growth factor receptor 3 (VEGFR3)-expressing macrophages infiltrating chemotherapy-treated tumors play a significant role in metastasis. They do so in part by inducing lymphangiogenesis as a result of cathepsin release, leading to VEGF-C upregulation by heparanase. We found that macrophages from chemotherapy-treated mice are sufficient to trigger lymphatic vessel activity and structure in naive tumors in a VEGFR3-dependent manner. Blocking VEGF-C/VEGFR3 axis inhibits the activity of chemotherapy-educated macrophages, leading to reduced lymphangiogenesis in treated tumors. Overall, our results suggest that disrupting the VEGF-C/VEGFR3 axis not only directly inhibits lymphangiogenesis but also blocks the pro-metastatic activity of macrophages in chemotherapy-treated mice

Patterns of care and dropout rates from outpatient mental healthcare in low-, middle- and high-income countries from the World Health Organization’s World Mental Health Survey Initiative

Background:There is a substantial proportion of patients who drop out of treatment beforethey receive minimally adequate care. They tend to have worse health outcomes than thosewho complete treatment. Our main goal is to describe the frequency and determinants ofdropout from treatment for mental disorders in low-, middle-, and high-income countries.Methods: Respondents from 13 low- or middle-income countries (N= 60 224) and 15 in high-income countries (N= 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for thosewho screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function. Results: Dropout rates are high, both in high-income (30%) and low/middle-income (45%)countries. Dropout mostly occurs during the first two visits. It is higher in general medicalrather than in specialist settings (nearly 60%v.20% in lower income settings). It is also higherfor mild and moderate than for severe presentations. The lack of financial protection for men-tal health services is associated with overall increased dropout from care.Conclusions:Extending financial protection and coverage for mental disorders may reducedropout. Efficiency can be improved by managing the milder clinical presentations at theentry point to the mental health system, providing adequate training, support and specialistsupervision for non-specialists, and streamlining referral to psychiatrists for more severe casesPeer ReviewedPostprint (author's final draft