Regulation of CD4+NKG2D+ Th1 cells in patients with metastatic melanoma treated with sorafenib : role of IL-15Rα and NKG2D triggering

Beyond cancer-cell intrinsic factors, the immune status of the host has a prognostic impact on patients with cancer and influences the effects of conventional chemotherapies. Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents. Here, we show that a multi-tyrosine kinase inhibitor, sorafenib, upregulates interleukin (IL)-15Rα in vitro and in vivo in patients with melanoma, and in conjunction with natural killer (NK) group 2D (NKG2D) ligands, contributes to the Th1 polarization and accumulation of peripheral CD4+NKG2D+ T cells. Hence, the increase of blood CD4+NKG2D+ T cells after two cycles of sorafenib (combined with temozolomide) was associated with prolonged survival in a prospective phase I/II trial enrolling 63 patients with metastatic melanoma who did not receive vemurafenib nor immune checkpoint-blocking antibodies. In contrast, in metastatic melanoma patients treated with classical treatment modalities, this CD4+NKG2D+ subset failed to correlate with prognosis. These findings indicate that sorafenib may be used as an "adjuvant" molecule capable of inducing or restoring IL-15Rα/IL-15 in tumors expressing MHCclass I-related chain A/B (MICA/B) and on circulating monocytes of responding patients, hereby contributing to the bioactivity of NKG2D+ Th1 cells.peer-reviewe

The relationship between childhood adversity, recent stressors, and depression in college students attending a South African university

Background College students are at risk of depression. This risk may be increased by the experience of childhood adversity and/or recent stressors. This study examined the association between reported experiences of childhood adversity, recent stressors and depression during the last 12 months in a cohort of South African university students. Methods Six hundred and eighty-six first year students at Stellenbosch University in South Africa completed a health-focused e-survey that included items on childhood adversity, recent stressors and mood. Individual and population attributable risk proportions (PARP) between experiences of childhood adversity and 12-month stressful experiences and 12-month depression were estimated using multivariate binomial logistic regression analysis. Results About one in six students reported depression during the last 12 months. Being a victim of bullying and emotional abuse or emotional neglect during childhood were the strongest predictors of depression in the past year at both individual and population level. With regard to recent stressors, a romantic partner being unfaithful, serious ongoing arguments or break-ups with some other close friend or family member and a sexual or gender identity crisis were the strongest predictors of depression. The predictor effect of recent stressors was significantly reduced in the final model that adjusted for the type and number of childhood traumatic experiences. At a population level, academic stress, serious ongoing arguments or break-ups with a close friend or family member, and serious betrayal by someone close were the variables that yielded the highest PARP. Conclusions Our findings suggest a significant relationship between early adversity, recent stressors, and depression here and throughout, consistent with the broader literature on predictors of depression. This study contributes to the limited data on college students’ mental health in low and middle income countries including on the African continent. The findings provide information on the population level effect sizes of trauma as a risk factor for depression, as well as on the relationship between specific recent stressors and depression in college students

The MACC-II 2007-2008 reanalysis: atmospheric dust validation and characterization over northern Africa and Middle East

Presentación realizada en: MACC-II Open Science Conference celebrada en Bruselas del 27 al 30 de enero de 2014

The importance of physical and mental health in explaining health-related academic role impairment among college students

Research consistently documents high rates of mental health problems among college students and strong associations of these problems with academic role impairment. Less is known, though, about prevalence and effects of physical health problems in relation to mental health problems. The current report investigates this by examining associations of summary physical and mental health scores from the widely-used Short-Form 12 (SF-12) Health Survey with self-reported academic role functioning in a self-report survey of 3,855 first-year students from five universities in the northeastern United States (US; mean age 18.5; 53.0% female). The mean SF-12 physical component summary (PCS) score (55.1) was half a standard deviation above the benchmark US adult population mean. The mean SF-12 mental component summary (MCS) score (38.2) was more than a full standard deviation below the US adult population mean. Two-thirds of students (67.1%) reported at least mild and 10.5% severe health-related academic role impairment on a modified version of the Sheehan Disability Scale. Both PCS and MCS scores were significantly and inversely related to these impairment scores, but with nonlinearities and interactions and much stronger associations involving MCS than PCS. Simulation suggests that an intervention that improved the mental health of all students with scores below the MCS median to be at the median would result in a 61.3% reduction in the proportion of students who experienced severe health-related academic role impairment. Although low-cost scalable interventions exist to address student mental health problems, pragmatic trials are needed to evaluate the effectiveness of these interventions in reducing academic role impairment

Reduced Cortisol Metabolism during Critical Illness

Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism.status: publishe

The MACC-II 2007–2008 reanalysis: atmospheric dust evaluation and characterization over northern Africa and the Middle East

In the present work, atmospheric mineral dust from a MACC-II short reanalysis run for 2 years (2007–2008) has been evaluated over northern Africa and the Middle East using satellite aerosol products (from MISR, MODIS and OMI satellite sensors), ground-based AERONET data, in situ PM10 concentrations from AMMA, and extinction vertical profiles from two ground-based lidars and CALIOP satellite-based lidar. The MACC-II aerosol optical depth (AOD) spatial and temporal (seasonal and interannual) variability shows good agreement with those provided by satellite sensors. The capability of the model to reproduce the AOD, Ångström exponent (AE) and dust optical depth (DOD) from daily to seasonal time-scale is quantified over 26 AERONET stations located in eight geographically distinct regions by using statistical parameters. Overall DOD seasonal variation is fairly well simulated by MACC-II in all regions, although the correlation is significantly higher in dust transport regions than in dust source regions. The ability of MACC-II in reproducing dust vertical profiles has been assessed by comparing seasonal averaged extinction vertical profiles simulated by MACC-II under dust conditions with corresponding extinction profiles obtained with lidar instruments at M'Bour and Santa Cruz de Tenerife, and with CALIOP.This work has been supported by EU-project Monitoring Atmospheric Composition and Climate (MACC-II) under the European Union Seventh Framework Programme, grant agreement number 283576. J. M. Baldasano and S. Basart acknowledge the Severo Ochoa (SEV-2011-00067) program of the Spanish Government and the mobility program from the Catalan Government (BE-DGR 2012)

The impact of lifetime suicidality on academic performance in college freshmen

Background While suicidal thoughts and behaviors (STB) among college students are common, the associations between STB and academic performance are not well understood. Methods As part of the World Mental Health Surveys International College Student project, web-based self-reported STB of KU Leuven (Leuven, Belgium) incoming freshmen (N=4921; response rate=65.4%) was collected, as well as academic year percentage (AYP), and the departments to which students belong. Single- and multilevel multivariate analyses were conducted, adjusted for gender, age, parental educational level, and comorbid lifetime emotional problems. Results Lifetime suicide plan and attempt upon college entrance were associated with significant decreases in AYP (3.6% and 7.9%, respectively). A significant interaction was found with average departmental AYP, with STB more strongly associated with reduced AYP in departments with lower than higher average AYP. Limitations Limited sample size precluded further investigation of interactions between department-level and student-level variables. No information was available on freshman secondary school academic performance. Conclusions Lifetime STB has a strong negative association with academic performance in college. Our study suggests a potential role for the college environment as target for treatment and prevention interventions.Psycholog

Thirty-day suicidal thoughts and behaviours in the Spanish adult general population during the first wave of the Spain COVID-19 pandemic

To investigate the prevalence of suicidal thoughts and behaviours (STB; i.e. suicidal ideation, plans or attempts) in the Spanish adult general population during the first wave of the Spain coronavirus disease 2019 (COVID-19) pandemic (March−July, 2020), and to investigate the individual- and population-level impact of relevant distal and proximal STB risk factor domains. Cross-sectional study design using data from the baseline assessment of an observational cohort study (MIND/COVID project). A nationally representative sample of 3500 non-institutionalised Spanish adults (51.5% female; mean age = 49.6 [ = 17.0]) was taken using dual-frame random digit dialing, stratified for age, sex and geographical area. Professional interviewers carried out computer-assisted telephone interviews (1-30 June 2020). Thirty-day STB was assessed using modified items from the Columbia Suicide Severity Rating Scale. Distal (i.e. pre-pandemic) risk factors included sociodemographic variables, number of physical health conditions and pre-pandemic lifetime mental disorders; proximal (i.e. pandemic) risk factors included current mental disorders and a range of adverse events-experiences related to the pandemic. Logistic regression was used to investigate individual-level associations (odds ratios [OR]) and population-level associations (population attributable risk proportions [PARP]) between risk factors and 30-day STB. All data were weighted using post-stratification survey weights. Estimated prevalence of 30-day STB was 4.5% (1.8% active suicidal ideation; n = 5 [0.1%] suicide attempts). STB was 9.7% among the 34.3% of respondents with pre-pandemic lifetime mental disorders, and 1.8% among the 65.7% without any pre-pandemic lifetime mental disorder. Factors significantly associated with STB were pre-pandemic lifetime mental disorders (total PARP = 49.1%) and current mental disorders (total PARP = 58.4%), i.e. major depressive disorder (OR = 6.0; PARP = 39.2%), generalised anxiety disorder (OR = 5.6; PARP = 36.3%), post-traumatic stress disorder (OR = 4.6; PARP = 26.6%), panic attacks (OR = 6.7; PARP = 36.6%) and alcohol/substance use disorder (OR = 3.3; PARP = 5.9%). Pandemic-related adverse events-experiences associated with STB were lack of social support, interpersonal stress, stress about personal health and about the health of loved ones (PARPs 32.7-42.6%%), and having loved ones infected with COVID-19 (OR = 1.7; PARP = 18.8%). Up to 74.1% of STB is potentially attributable to the joint effects of mental disorders and adverse events−experiences related to the pandemic. STB at the end of the first wave of the Spain COVID-19 pandemic was high, and large proportions of STB are potentially attributable to mental disorders and adverse events−experiences related to the pandemic, including health-related stress, lack of social support and interpersonal stress. There is an urgent need to allocate resources to increase access to adequate mental healthcare, even in times of healthcare system overload. NCT0455656