Use and misuse of multivariable approaches in interventional cardiology studies on drug-eluting stents: a systematic review.

Aims: Randomized clinical trials (RCTs) are the most reliable evidence, even if they require important resource and logistic efforts. Large, cost-free and real-world datasets may be easily accessed yielding to observational studies, but such analyses often lead to problematic results in the absence of careful methods, especially from a statistic point of view. We aimed to appraise the performance of current multivariable approaches in the estimation of causal treatment and effects in studies focusing on drug-eluting stents (DES). Methods and Results: Pertinent studies published in the literature were searched, selected, abstracted, and appraised for quality and validity features. Six studies with a logistic regression were included, all of them reporting more than 10 events for covariates and different length of follow-up, with an overall low risk of bias. Most of the 15 studies with a Cox proportional hazard analysis had a different follow-up, with less than 10 events for covariates, yielding an overall low or moderate risk of bias. Sixteen studies with propensity score were included: the most frequent method for variable selection was logistic regression, with underlying differences in follow-up and less than 10 events for covariate in most of them. Most frequently, calibration appraisal was not reported in the studies, on the contrary of discrimination appraisal, which was more frequently performed. In seventeen studies with propensity and matching, the latter was most commonly performed with a nearest neighbor-matching algorithm yet without appraisal in most of the studies of calibration or discrimination. Balance was evaluated in 46% of the studies, being obtained for all variables in 48% of them. Conclusions: Better exploitation and methodological appraisal of multivariable analysis is needed to improve the clinical and research impact and reliability of nonrandomized studies. (J Interven Cardiol 2012;**:1-1

Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation

Background: Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. Objectives: We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 μm (PM10). Methods: We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM10 exposure was between 73.4 and 1,220 μg/m3. Results: Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM10 exposure levels were negatively associated with methylation in both Alu [β = –0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [β = –0.34 %5mC; p = 0.04], likely reflecting long-term PM10 effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = –0.61 %5mC; p = 0.02). Conclusions: We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM

Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy

There are no robust data on the real onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and spread in the prepandemic period worldwide. We investigated the presence of SARS-CoV-2 receptor-binding domain (RBD)–specific antibodies in blood samples of 959 asymptomatic individuals enrolled in a prospective lung cancer screening trial between September 2019 and March 2020 to track the date of onset, frequency, and temporal and geographic variations across the Italian regions. SARS-CoV-2 RBD-specific antibodies were detected in 111 of 959 (11.6%) individuals, starting from September 2019 (14%), with a cluster of positive cases (&gt;30%) in the second week of February 2020 and the highest number (53.2%) in Lombardy. This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. Finding SARS-CoV-2 antibodies in asymptomatic people before the COVID-19 outbreak in Italy may reshape the history of pandemic

TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: A meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients.

BACKGROUND: Acute coronary syndromes (ACS) represent a difficult challenge for physicians. Risk scores have become the cornerstone in clinical and interventional decision making. METHODS AND RESULTS: PubMed was systematically searched for ACS risk score studies. They were divided into ACS studies (evaluating Unstable Angina; UA, Non ST Segment Elevation Myocardial Infarction; NSTEMI, and ST Segment Elevation Myocardial Infarction; STEMI), UA/NSTEMI studies or STEMI studies. The c-statistics of validation studies were pooled when appropriate with random-effect methods. 7 derivation studies with 25,525 ACS patients and 15 validation studies including 257,654 people were formally appraised. Pooled analysis of GRACE scores, both at short (0.82; 0.80-0.89 I.C 95%) and long term follow up (0.84; 0.82-0.87; I.C 95%) showed the best performance, with similar results to Simple Risk Index (SRI) derivation cohorts at short term. For NSTEMI/UA, 18 derivation studies with 56,560 patients and 18 validation cohorts with 56,673 patients were included. Pooled analysis of validations studies showed c-statistics of 0.54 (95% CI = 0.52-0.57) and 0.67 (95% CI = 0.62-0.71) for short and long term TIMI validation studies, and 0.83 (95% CI = 0.79-9.87) and 0.80 (95% CI = 0.74-0.89) for short and long term GRACE studies. For STEMI, 15 studies with 134,557 patients with derivation scores, and 17 validation studies with 187,619 patients showed a pooled c-statistic of 0.77 (95% CI = 0.71-0.83) and 0.77 (95% CI = 0.72-0.85) for TIMI at short and long term, and a pooled c-statistic of 0.82 (95% CI = 0.81-0.83) and 0.81 (95% CI = 0.80-0.82) for GRACE at short and long terms respectively. CONCLUSIONS: TIMI and GRACE are the risk scores that up until now have been most extensively investigated, with GRACE performing better. There are other potentially useful ACS risk scores available however these have not undergone rigorous validation. This study suggests that these other scores may be potentially useful and should be further researched

Implicancias del estrés hídrico en la calidad forrajera de Cenchrus ciliaris L.

Las colecciones de germoplasma representan un punto de partida importante para el mantenimiento y multiplicación de fuentes genéticas y la evaluación de la potencialidad de especies para diferentes destinos productivos. El estudio de especies forrajeras promisorias para la alimentación animal se basa en aspectos agronómicos, productivos y de calidad1. La calidad de una pastura está asociada con la anatomía foliar y sus tejidos constituyentes, el contenido de pared celular (determinante de la rigidez), las condiciones ambientales y el estado fenológico2. El objetivo de nuestro trabajo fue evaluar el efecto de estrés hídrico en estadío de plántula y su relación con calidad forrajera en los genotipos RN51 (de comportamiento tolerante) y RN1 (susceptible) de Cenchrus ciliaris L. Se midieron parámetros fisiológicos, anatómicos, morfo-agronómicos y moleculares. El ensayo consistió de los tratamientos: Control (80% capacidad de campo (CC)) y sequía (20%CC, 21 días). Al final de cada tratamiento, se midieron contenido relativo de agua, eficiencia cuántica máxima (Fv/Fm) del PSII, evapotranspiración, altura, peso fresco y peso seco. El genotipo susceptible mostrólos mayores valores de daño (evaluado como proporción entre la condición de estrés y la media del control, para cada tratamiento y genotipo) para las variables fisiológicas y morfo-agronómicas. En las variables anatómicas (medidas en lámina), el genotipo tolerante mostró aumento en el área del esclerénquima, mayor grosor de la epidermis adaxial y menor relación parénquima:esclerénquima que el genotipo susceptible y además exhibió la formación de células buliformes al ser expuesto a estrés hídrico. Asimismo, dicho genotipo incrementó la expresión de genes relacionados con la biosíntesis de la lignina en condiciones de sequía. Este estudio es el primer antecedente en Cenchrus ciliaris que evidencia la asociación negativa entre el proceso de lignificación, determinante de la calidad forrajera y tolerancia al estrés hídrico

Psychobiological evidence of the stress resilience fostering properties of a cosmetic routine

Everyday life psychosocial stressors contribute to poor health and disease vulnerabilty. Means alternative to pharmacotherapy that are able to foster stress resilience are more and more under the magnifying glass of biomedical research. The aim of this study was to test stress resilience fostering properties of the self-administration of a cosmetic product enriched with essential oils. On day 0, fourty women, 25-50 years old, self-administered both the enriched cosmetic product (ECP) and a placebo one (PCP). Then, women were randomized for daily self-administration (from day 1 to 28) of either ECP

Correlation of Global and Gene-Specific DNA Methylation in Maternal-Infant Pairs

The inheritance of DNA methylation patterns is a popular theory to explain the influence of parental genetic and environmental factors on the phenotype of their offspring but few studies have examined this relationship in humans. Using 120 paired maternal-umbilical cord blood samples randomly selected from a prospective birth cohort in Bangladesh, we quantified DNA methylation by pyrosequencing seven CpG positions in the promoter region of p16, four CpG positions in the promoter region of p53, LINE-1 and Alu. Positive correlations were observed between maternal and umbilical cord blood at p16, LINE-1, and Alu but not p53. Multiple linear regression models observed a significant association between maternal and umbilical cord blood at LINE-1 and Alu (LINE-1: β = 0.63, p<0.0001; Alu: β = 0.28, p = 0.009). After adjusting for multiple comparisons, maternal methylation of p16 at position 4 significantly predicted methylation at the same position in umbilical cord blood (β = 0.43, p = <0.0001). These models explained 48%, 5% and 16% of the observed variability in umbilical cord %5mC for LINE-1, Alu and p16 at position 4, respectively. These results suggest that DNA methylation in maternal blood was correlated with her offspring at LINE-1, Alu, and p16 but not p53. Additional studies are needed to confirm whether these observed associations were due to the inheritance of epigenetic events or the shared environment between mother and fetus. Future studies should also use a multi-generational family-based design that would quantify both maternal and paternal contributions to DNA methylation in offspring across more than one generation

Agronomic and molecular characterization of <i>Chloris gayana</i> cultivars and salinity response during germination and early vegetative growth

Chloris gayana is a warm-season grass, often cultivated in areas where soil salinity is a major constraint for forage production. Five cultivars (2 unselected populations and 3 synthetic varieties) were evaluated through agronomic traits as well as Inter Simple Sequence Repeats (ISSRs) and Sequence-related Amplified Polymorphism (SRAP) molecular markers. The consensus between both agronomic and molecular data sets was high (>99%) suggesting that both systems provided similar estimates of genetic relationships. The analysis revealed that synthetic varieties, Finecut, Topcut and Santana, were the most genetically different cultivars, whereas the unselected populations, Pioneer and Katambora, were closely related. Responses to salinity stress during germination and early vegetative growth stages were evaluated in only the synthetic varieties. The results showed that Finecut and Santana were able to germinate in the same proportion as controls even at concentrations of 200 mM NaCl. Under hydroponic conditions, Santana attained approximately 20% higher total dry weight than the other 2 varieties and the longest roots. Finecut presented the highest root dry weight. These results suggested that Santana and Finecut showed high salinity tolerance at germination and early vegetative growth stages, both crucial phases when seeking a successful pasture establishment, particularly in saline environments. Further studies in the field are needed to determine if these hydroponic results are reproduced under field conditions