Using newspaper obituaries to “nowcast” daily mortality: Evidence from the Italian COVID-19 hot-spots

Real-time tracking of epidemic helps governments and health authorities make timely data-driven decisions. Official mortality data, whenever reliable and available, is usually published with a substantial delay. We report results of using newspapers obituaries to “nowcast” the mortality levels observed in Italy during the COVID-19 outbreak between February 24, 2020 and April 15, 2020. Mortality levels predicted using obituaries outperform forecasts based on past mortality according to several performance metrics, making obituaries a potentially valid alternative source of information to deal with epidemic surveillance.     

A Generalized Entropy Measure of Within-Host Viral Diversity for Identifying Recent HIV-1 Infections

There is a need for incidence assays that accurately estimate HIV incidence based on cross-sectional specimens. Viral diversity-based assays have shown promises but are not particularly accurate. We hypothesize that certain viral genetic regions are more predictive of recent infection than others and aim to improve assay accuracy by using classification algorithms that focus on highly informative regions (HIRs).We analyzed HIV gag sequences from a cohort in Botswana. Forty-two subjects newly infected by HIV-1 Subtype C were followed through 500 days post-seroconversion. Using sliding window analysis, we screened for genetic regions within gag that best differentiate recent versus chronic infections. We used both nonparametric and parametric approaches to evaluate the discriminatory abilities of sequence regions. Segmented Shannon Entropy measures of HIRs were aggregated to develop generalized entropy measures to improve prediction of recency. Using logistic regression as the basis for our classification algorithm, we evaluated the predictive power of these novel biomarkers and compared them with recently reported viral diversity measures using area under the curve (AUC) analysis.Change of diversity over time varied across different sequence regions within gag. We identified the top 50% of the most informative regions by both nonparametric and parametric approaches. In both cases, HIRs were in more variable regions of gag and less likely in the p24 coding region. Entropy measures based on HIRs outperformed previously reported viral-diversity-based biomarkers. These methods are better suited for population-level estimation of HIV recency.The patterns of diversification of certain regions within the gag gene are more predictive of recency of infection than others. We expect this result to apply in other HIV genetic regions as well. Focusing on these informative regions, our generalized entropy measure of viral diversity demonstrates the potential for improving accuracy when identifying recent HIV-1 infections.     

Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease

Metabolic heart disease (MHD), which is strongly associated with heart failure with preserved ejection fraction, is characterized by reduced mitochondrial energy production and contractile performance. In this study, we tested the hypothesis that an acute increase in ATP synthesis, via short chain fatty acid (butyrate) perfusion, restores contractile function in MHD. Isolated hearts of mice with MHD due to consumption of a high fat high sucrose (HFHS) diet or on a control diet (CD) for 4 months were studied using ³¹P NMR spectroscopy to measure high energy phosphates and ATP synthesis rates during increased work demand. At baseline, HFHS hearts had increased ADP and decreased free energy of ATP hydrolysis (ΔG _{~ ATP}), although contractile function was similar between the two groups. At high work demand, the ATP synthesis rate in HFHS hearts was reduced by over 50%. Unlike CD hearts, HFHS hearts did not increase contractile function at high work demand, indicating a lack of contractile reserve. However, acutely supplementing HFHS hearts with 4mM butyrate normalized ATP synthesis, ADP, ΔG _{~ ATP} and contractile reserve. Thus, acute reversal of depressed mitochondrial ATP production improves contractile dysfunction in MHD. These findings suggest that energy starvation may be a reversible cause of myocardial dysfunction in MHD, and opens new therapeutic opportunities.     

Obesity and Excess Protein and Carbohydrate Consumption Are Risk Factors for Thyroid Cancer

Conflicting data concerning the association between obesity and differentiated thyroid cancer (DTC) may be attributed to the lack of records showing dietary intake and inadequate evaluation of nutrient composition. We evaluated 115 DTC patients carefully paired with 103 healthy control individuals by using a structured questionnaire, including a 24-h recordatory during 3 days, to investigate calorie intake and macronutrient (proteins, carbohydrates, and lipids) composition of the diet. We observed that excess weight (body mass index > 25 kg/m²) increased individual susceptibility to DTC [odds ratio (OR) = 3.787; 95% confidence interval (CI) = 1.115–6.814; P < 0.0001). This augmented risk was evident in women (OR = 1.925; 95% CI = 1.110–3.338; P = 0.0259) but not in men (P = 0.3498). Excess calorie intake was more frequent in patients with DTC than in controls (OR = 5.890; 95% CI = 3.124–11.103; P < 0.0001), and both excess protein (OR = 4.601; 95% CI = 1.634–12.954; P = 0.0039) and carbohydrate (OR = 4.905; 95% CI = 2.593–9.278; P < 0.0001) consumption were associated with an increased risk of DTC, contrarily to lipid/fiber intake and physical activity (P = 0.894 and 0.5932, respectively). In conclusion, our data indicate that overweight and risk of DTC are associated with higher protein and carbohydrate consumption than the rates recommended by the World Health Organization. The nutritional orientation should be part of preventive strategy targets designed to combat the increasing incidence of both obesity and DTC.     

Consenso sobre Ecocardiografia Transesofágica Perioperatória da Sociedade Brasileira de Anestesiologia e do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia

Through the Life Cycle of Intraoperative Transesophageal Echocardiography (ETTI/SBA) the Brazilian Society of Anesthesiology, together with the Department of Cardiovascular Image of the Brazilian Society of Cardiology (DIC/SBC), createded a task force to standardize the use of intraoperative transesophageal echocardiography by Brazilian anesthesiologists and echocardiographers based on scientific evidence from the Society of Cardiovascular Anesthesiologists/American Society of Echocardiography (SCA/ASE) and the Brazilian Society of Cardiology.     

GPCRs and cancer

G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients.