Cancer: Linking Powerhouses to Suicidal Bags.

Membrane-bound organelles are integrated into cellular networks and work together for a common goal: regulating cell metabolism, cell signaling pathways, cell fate, cellular maintenance, and pathogen defense. Many of these interactions are well established, but little is known about the interplay between mitochondria and lysosomes, and their deregulation in cancer. The present review focuses on the common signaling pathways of both organelles, as well as the processes in which they both physically interact, their changes under pathological conditions, and the impact on targeting those organelles for treating cancer

Dietary animal and plant protein intakes and their associations with obesity and cardio-metabolic indicators in European adolescents: The HELENA cross-sectional study

Background: Previous studies suggest that dietary protein might play a beneficial role in combating obesity and its related chronic diseases. Total, animal and plant protein intakes and their associations with anthropometry and serum biomarkers in European adolescents using one standardised methodology across European countries are not well documented. Objectives: To evaluate total, animal and plant protein intakes in European adolescents stratified by gender and age, and to investigate their associations with cardio-metabolic indicators (anthropometry and biomarkers). Methods: The current analysis included 1804 randomly selected adolescents participating in the HELENA study (conducted in 2006-2007) aged 12.5-17.5 y (47% males) who completed two non-consecutive computerised 24-h dietary recalls. Associations between animal and plant protein intakes, and anthropometry and serum biomarkers were examined with General linear Model multivariate analysis. Results: Average total protein intake exceeded the recommendations of World Health Organization and European Food Safety Authority. Mean total protein intake was 96 g/d (59% derived from animal protein). Total, animal and plant protein intakes (g/d) were significantly lower in females than in males and total and plant protein intakes were lower in younger participants (12.5-14.9 y). Protein intake was significantly lower in underweight subjects and higher in obese ones; the direction of the relationship was reversed after adjustments for body weight (g/(kg.d)). The inverse association of plant protein intakes was stronger with BMI z-score and body fat percentage (BF%) compared to animal protein intakes. Additionally, BMI and BF% were positively associated with energy percentage of animal protein. Conclusions: This sample of European adolescents appeared to have adequate total protein intake. Our findings suggest that plant protein intakes may play a role in preventing obesity among European adolescents. Further longitudinal studies are needed to investigate the potential beneficial effects observed in this study in the prevention of obesity and related chronic diseases

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

High Diazotrophic Diversity but Low N2 Fixation Activity in the Northern Benguela Upwelling System Confirming the Enigma of Nitrogen Fixation in Oxygen Minimum Zone Waters

Oxygen minimum zones (OMZs) have been suggested as a suitable niche for the oxygen-sensitive process of biological fixation of dinitrogen (N2) gas. However, most N2 fixation rates reported from such waters are low. This low N2 fixation activity has been proposed to result from the unusual community of N2 fixers, in which cyanobacteria were typically underrepresented. The Northern Benguela Upwelling System (North BUS) is part of one of the most productive marine ecosystems and hosts a well-developed OMZ. Although previous observations indicated low to absent N2 fixation rates, the community composition of diazotrophs needed to understand the North BUS has not been described. Here, we present a first detailed analysis of the diazotrophic diversity in the North BUS OMZ and the Angola tropical zone (ATZ), based on genetic data and isotope speciation. Consistent with a previous study, we detected a slight N deficit in the OMZ, but isotope data did not indicate any active or past N2 fixation. The diazotroph community in the North BUS was dominated by non-cyanobacterial microbes clustering with members of gamma-proteobacteria, as is typical for other OMZ regions. However, we found a strikingly high diversity of Cluster III diazotrophs not yet described in other OMZs. In contrast to previous observations, we could also identify cyanobacteria of the clades Trichodesmium sp., UCYN-A and Cyanothece sp., in surface waters connected to or above the OMZ, which were potentially active as shown by the presence of genes and transcripts of the key functional marker gene for N2 fixation, nifH. While the detection of diazotrophs and the absence of active N2 fixation (based on isotopic speciation) are consistent with other OMZ observations, the detected regional variation in the diversity and presence of cyanobacteria indicate that we still are far from understanding the role of diazotrophs in OMZs, which, however, is relevant for understanding the N cycle in OMZ waters, as well for predicting the future development of OMZ biogeochemistry in a changing ocean

Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues.

This study investigated the role of CDK4 in the oxidative metabolism of brown adipose tissue (BAT). BAT from Cdk4 <sup>-/-</sup> mice exhibited fewer lipids and increased mitochondrial volume and expression of canonical thermogenic genes, rendering these mice more resistant to cold exposure. Interestingly, these effects were not BAT cell-autonomous but rather driven by increased sympathetic innervation. In particular, the ventromedial hypothalamus (VMH) is known to modulate BAT activation via the sympathetic nervous system. We thus examined the effects of VMH neuron-specific Cdk4 deletion. These mice display increased sympathetic innervation and enhanced cold tolerance, similar to Cdk4 <sup>-/-</sup> mice, in addition to browning of scWAT. Overall, we provide evidence showing that CDK4 modulates thermogenesis by regulating sympathetic innervation of adipose tissue depots through hypothalamic nuclei, including the VMH. This demonstrates that CDK4 not only negatively regulates oxidative pathways, but also modulates the central regulation of metabolism through its action in the brain

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice : A multicentre cohort study

Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization

Correlates of ideal cardiovascular health in European adolescents: The HELENA study

The ideal cardiovascular health (iCVH) construct consists of 4 health behaviors (smoking status, body mass index, physical activity and diet) and 3 health factors (total cholesterol, blood pressure and fasting glucose). A greater number of iCVH components in adolescence are related to better cardiovascular health, but little is known about the correlates of iCVH in adolescents. Thus, the aim of the study was to examine correlates of iCVH in European adolescents. METHODS AND RESULTS: The study comprised 637 European adolescents with complete iCVH data. Participants were part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional, multicenter study conducted in 9 different European countries. Correlates investigated were sex and age, family affluence scale, maternal education, geographic location, sleep time, television viewing, duration of pregnancy, birth weight and breastfeeding. Younger adolescents, those whose mothers had medium/high education or those who watched television less than 2 h per day had a greater number of iCVH components compared to those who were older, had a mother with low education or watched television 2 h or more daily (P ≤ 0.01). CONCLUSION: Since in our study older adolescents had worse iCVH than younger adolescents, early promotion of cardiovascular health may be important. Future studies may also investigate the usefulness of limiting television viewing to promote iCVH. Finally, since adolescents of mothers with low education had poorer iCVH, it may be of special interest to tailor public health promotion to adolescents from families with low socioeconomic status