Therapeutic potential of emerging NAD+-increasing strategies for cardiovascular diseases

Altres ajuts: Fundació La Marató de TV3 (303/C/2016)(201602.30.31)Cardiovascular diseases are the leading cause of death worldwide. Aging and/or metabolic stress directly impact the cardiovascular system. Over the last few years, the contributions of altered nicotinamide adenine dinucleotide (NAD+) metabolism to aging and other pathological conditions closely related to cardiovascular diseases have been intensively investigated. NAD+ bioavailability decreases with age and cardiometabolic conditions in several mammalian tissues. Compelling data suggest that declining tissue NAD+ is commonly related to mitochondrial dysfunction and might be considered as a therapeutic target. Thus, NAD+ replenishment by either genetic or natural dietary NAD+-increasing strategies has been recently demonstrated to be effective for improving the pathophysiology of cardiac and vascular health in different experimental models, as well as human health, to a lesser extent. Here, we review and discuss recent experimental evidence illustrating that increasing NAD+ bioavailability, particularly by the use of natural NAD+ precursors, may offer hope for new therapeutic strategies to prevent and treat cardiovascular diseases

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Super Learner Analysis of Real-Time Electronically Monitored Adherence to Antiretroviral Therapy under Constrained Optimization and Comparison to Non-Differentiated Care Approaches for Persons Living with HIV in Rural Uganda

Introduction Real‐time electronic adherence monitoring (EAM) systems could inform on‐going risk assessment for HIV viraemia and be used to personalize viral load testing schedules. We evaluated the potential of real‐time EAM (transferred via cellular signal) and standard EAM (downloaded via USB cable) in rural Uganda to inform individually differentiated viral load testing strategies by applying machine learning approaches. Methods We evaluated an observational cohort of persons living with HIV and treated with antiretroviral therapy (ART) who were monitored longitudinally with standard EAM from 2005 to 2011 and real‐time EAM from 2011 to 2015. Super learner, an ensemble machine learning method, was used to develop a tool for targeting viral load testing to detect viraemia (\u3e1000 copies/ml) based on clinical (CD4 count, ART regimen), viral load and demographic data, together with EAM‐based adherence. Using sample‐splitting (cross‐validation), we evaluated area under the receiver operating characteristic curve (cvAUC), potential for EAM data to selectively defer viral load tests while minimizing delays in viraemia detection, and performance compared to WHO‐recommended testing schedules. Results In total, 443 persons (1801 person‐years) and 485 persons (930 person‐years) contributed to standard and real‐time EAM analyses respectively. In the 2011 to 2015 dataset, addition of real‐time EAM (cvAUC: 0.88; 95% CI: 0.83, 0.93) significantly improved prediction compared to clinical/demographic data alone (cvAUC: 0.78; 95% CI: 0.72, 0.86; p = 0.03). In the 2005 to 2011 dataset, addition of standard EAM (cvAUC: 0.77; 95% CI: 0.72, 0.81) did not significantly improve prediction compared to clinical/demographic data alone (cvAUC: 0.70; 95% CI: 0.64, 0.76; p = 0.08). A hypothetical testing strategy using real‐time EAM to guide deferral of viral load tests would have reduced the number of tests by 32% while detecting 87% of viraemia cases without delay. By comparison, the WHO‐recommended testing schedule would have reduced the number of tests by 69%, but resulted in delayed detection of viraemia a mean of 74 days for 84% of individuals with viraemia. Similar rules derived from standard EAM also resulted in potential testing frequency reductions. Conclusions Our machine learning approach demonstrates potential for combining EAM data with other clinical measures to develop a selective testing rule that reduces number of viral load tests ordered, while still identifying those at highest risk for viraemia

Greenhouse Gas Emission Scenarios and Vehicle Engine Performance in a Main Urban Road in Northwestern Mexico

Transport is one of the sectors with the highest greenhouse gas emissions (GHG) that is imperative to reduce in order to decrease global warming. Although modern vehicles and arterial roads have adopted technological and structural improvements to enhance fuel use efficiency, the emission of greenhouse gases (GHG) into the atmosphere by the transport sector has been increasing in different Mexican cities. In generating mitigation strategies, modeling scenarios of decreased equivalent carbon dioxide, CO2e emissions, may be useful as an evaluation tool. In this study, the aim was to model a trend scenario and a scenario, including improvements with a projection to the year 2039 on one of the main urban roads of the border city of Mexicali, Mexico. In order to create a dynamic emission model of GHG, including emission factors, the main variables for the simulation were vehicle volume, travels, motor performance, and fuel consumption. These last two parameters were the most important for vehicular emissions estimations and for the projection of them in this period. As a result of the projections, CO2e was observed to increase in a trend scenario, while modeled improvement actions resulted in emission reductions of up to 5%. The model showed that the key variable to achieve this reduction is vehicle engine performance (Pf), whose increase factor was 1.1% per year. Replicating this methodology to evaluate and mitigate the GHG emissions on different city roads or in other cities, can be a contribution for the urban designers, authorities, and involved institutions

Mutagenicity evaluation caused by heavy metals found in Cauca river water in the city of Cali, Colombia

Se evaluó la mutagenicidad del agua del río Cauca debida a la presencia de metales pesados en la zona urbana de la Ciudad de Santiago de Cali, a partir de muestras tomadas en la temporada seca y lluviosa en el año 2013. Los metales se extrajeron pasando el agua por la resina Amberlite XAD-16. Las concentraciones de los metales pesados se midieron por absorción atómica y la mutagenicidad se evaluó por medio del test de Ames, con las cepas TA98 y TA100 de Salmonella typhimurium con y sin activador enzimático S9. Los resultados mostraron índices de mutagenicidad (IM) positivos (IM > 2,0) para muestras colectadas en temporada lluviosa en tres de los cinco puntos evaluados: puente El Hormiguero (IM = 3,6), desembocadura del Canal Colector Sur (IM = 2,9) y desembocadura del río Cali (IM = 2,7), todos con la cepa TA98 sin S9. Estos sitios presentaron a su vez las mayores concentraciones totales de metales pesados en sus extractos. El análisis de la variación espacio-temporal del índice mutagénico se realizó haciendo un análisis de varianza multifactorial del IM. Los resultados encontrados indican que la época de muestreo contribuye significativamente a la variabilidad del IM , mientras que los puntos de muestreo noThe mutagenicity of the Cauca River water due to the presence of heavy metals was evaluated in the urban area of the city of Santiago de Cali, from samples taken during the rainy and dry season of 2013. The metals were extracted from water samples using the resin Amberlite XAD-16. The concentrations of heavy metals were measured by atomic absorption and mutagenicity was evaluated by the Ames test, using the TA98 and TA100 strains of Salmonella typhimurium with and without the S9 enzymatic activator. The results showed mutagenicity indices (MI > 2.0) in three of the five points evaluated: El Hormiguero Bridge (MI = 3.6), the mouth of southern collector channel (MI = 2.9) and the mouth of Cali River (MI = 2.7), all with strain TA98 without S9. These sampling points in turn presented the highest total concentrations of heavy metals in the extracts. The determination and analysis of spatio-temporal variation of the mutagenic effects obtained was done by conducting multifactorial variance analysis of MI, finding that the effect of sampling season contributes significantly to the variability of MI unlike the sampling point

Visceral Adiposity Index in Breast Cancer Survivors: A Case-Control Study

Background. Breast cancer (BC) is the first cause of cancer morbidity and mortality in women. This disease has been linked to obesity; however, it is not clear how fat accumulation affects women who survive breast cancer. Although the visceral adiposity index (VAI) is a marker of cardiometabolic risk and adipose tissue dysfunction, it is not clear how it changes in breast cancer survivors. The aim of this investigation was to compare VAI in women with and without breast cancer. Methods. A case-control cross-sectional study was conducted on women who were BC survivors and women without the history of BC (control group). Body composition was assessed using electrical bioimpedance while VAI by means of waist circumference (WC), body mass index (BMI), triacylglycerols (TG), and high-density lipoprotein cholesterol (HDL-C). Results. 49 women in the BC survivor group and 50 in the control group. WC was wider in the survivor group as regards control (93.65 ± 10.48 vs. 88.52 ± 9.61 cm) (p=0.025); at once, TG and VAI were significantly higher for the survivor group (243.55 ± 199.84 vs. 159.84 ± 75.77) (p=0.007) and (11.03 ± 11.15 vs. 6.41 ± 3.66) (p<0.005), respectively. Body composition parameters were similar in both groups. Conclusions. VAI is higher in women who are BC survivors in comparison with controls matched by age and bodyweight

Chagas Disease in Pregnant Women from Endemic Regions Attending the Hospital General de Mexico, Mexico City

Trypanosoma cruzi infection leads to Chagas disease (CD), a neglected tropical infection of significant public health importance in South and Central America and other, non-endemic, countries. Pregnant women and their children are of particular importance to screen as T. cruzi can be transmitted vertically. The objective of this study was to screen for T. cruzi infection among pregnant women from endemic areas seen at the Hospital General de Mexico for prenatal care, so that they and their children may be quickly connected to CD treatment. Pregnant women were recruited through the hospital prenatal clinic and screened for T. cruzi infection using a series of serological and molecular tests. Of 150 screened patients, mean age 26.8 (SD 6.4), 30 (20.0%) were positive by at least one diagnostic test. Of these, only nine (6%) were positive as determined by PCR. Diagnosis of chronic CD is difficult in endemic places like Mexico due to the limitations of current commercially available diagnostic tests. Further evaluation of diagnostic performance of various assays could improve current CD diagnostic algorithms and proper care management in these regions. Genetic variability in the parasite may also play a role in the differing assay performances seen in this study, and this may be a valuable avenue of further research