New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effects Of High-dose Cisplatin Chemotherapy And Conventional Radiotherapy On Urinary Oxidative And Nitrosative Stress Biomarkers In Patients With Head And Neck

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Cisplatin is a chemotherapeutic agent widely used in the treatment of several solid tumours. For patients with advanced head and neck squamous cell carcinoma in whom surgery is contraindicated, treatment with high-dose cisplatin administered every 21 days for 3 cycles concomitantly with conventional radiotherapy is recommended [1-3]. Its anticancer mechanism is mediated by DNA binding, which leads to the formation of inter-and intrastrand crosslinks and results in defective DNA templates, arrest of DNA synthesis and replication, DNA damage and, finally, cell death [4]. In addition, cisplatin accumulates in human cells (normal and tumour cells) resulting in enhanced production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which leads to mitochondrial damage and dysfunction [5,6]. In addition, there is a decrease in the antioxidant defence system mediated primarily by links formed between cisplatin and glutathione, which culminates in the depletion of glutathione [7]. The excessive generation of ROS and RNS damages biomolecules, resulting in lipid, protein and DNA/RNA oxidation and causing toxicities including nephrotoxicity, neurotoxicity, ototoxicity and hepatotoxicity [8-11]. The intensity of biomolecular damage can be determined by oxidative/nitrosative stress biomarkers. In this study, we used malondialdehyde (MDA) and lipid hydroperoxides, which are indicators of lipid peroxidation/oxidative stress biomarkers and nitrite, a nitrosative stress biomarker. Therefore, the aim of this study was to determine the effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary levels of MDA, lipid hydroperoxides and nitrite biomarkers in patients with head and neck11818386Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary oxidative and nitrosative stress biomarkers in patients with head and neck

Cisplatin is a chemotherapeutic agent widely used in the treatment of several solid tumours. For patients with advanced head and neck squamous cell carcinoma in whom surgery is contraindicated, treatment with high-dose cisplatin administered every 21 days for 3 cycles concomitantly with conventional radiotherapy is recommended [1-3]. Its anticancer mechanism is mediated by DNA binding, which leads to the formation of inter-and intrastrand crosslinks and results in defective DNA templates, arrest of DNA synthesis and replication, DNA damage and, finally, cell death [4]. In addition, cisplatin accumulates in human cells (normal and tumour cells) resulting in enhanced production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which leads to mitochondrial damage and dysfunction [5,6]. In addition, there is a decrease in the antioxidant defence system mediated primarily by links formed between cisplatin and glutathione, which culminates in the depletion of glutathione [7]. The excessive generation of ROS and RNS damages biomolecules, resulting in lipid, protein and DNA/RNA oxidation and causing toxicities including nephrotoxicity, neurotoxicity, ototoxicity and hepatotoxicity [8-11]. The intensity of biomolecular damage can be determined by oxidative/nitrosative stress biomarkers. In this study, we used malondialdehyde (MDA) and lipid hydroperoxides, which are indicators of lipid peroxidation/oxidative stress biomarkers and nitrite, a nitrosative stress biomarker. Therefore, the aim of this study was to determine the effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary levels of MDA, lipid hydroperoxides and nitrite biomarkers in patients with head and neck11818386CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPES

Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

International audienceBackground: The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (&gt; 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods: Characteristics, management, and prognosis of critically ill old patients (&gt; 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results: The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO2/FiO2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO2/FiO2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p &lt; 0·001). Conclusion: Patients over 70 years old represented more than a quarter of the COVID-19 population admitted in the participating ICUs during the first wave. Day-90 mortality was 46%, with dismal outcomes reported for patients older than 80 years or those intubated upon ICU admission

Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems

We present the science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technology, that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field