Dendrochronological and geomorphological investigations to assess water erosion and mass wasting processes in the Apennines of Southern Tuscany (Italy)

The Tyrrhenian side of the Central Apennines is located in a lively geological context, in which uplift/denudation dynamics played a key role in landscape evolution. Intense water erosion and gravitational processes led to the development of spectacular badlands on the widespread clayey hillslopes. The Crete d'Arbia badlands (as part of the Crete Senesi of Southern Tuscany) represent one of the most beautiful examples of these landforms developed on Pliocene clays. On the other hand, these rapidly evolving landforms endanger the artistic heritage of the area, as with the Monte Oliveto Maggiore Abbey that was constructed on the top of a badland hillslope and confers additional value to the landscape.In the perspective of monitoring and reconstructing some significant phases of the relief evolution of this area an integrated approach has been used, which is based on dendrogeomorphology and geomorphological monitoring techniques. In particular, the correspondence between the data from dendrogeomorphological indicators and the measured denudation rates on badland hillslopes was tested. The sampling for dendrogeomorphological analysis has been performed in two stages on 45 trees of the Pinus pinea L. species, on hillslopes affected by soil creep and shallow landslides, in order to identify annual ring growth anomalies, compression wood and roots exposure. Trees' local behaviour is not homogeneous but some common trends have been detected on the basis of the anomaly index and compression wood. Since 1993 several monitoring stations at badland denudation "hot spots" have been equipped with erosion pins; quantitative data from monitoring stations, compared to pluviometric series, indicated critical phases of denudation that were supported by dendrochronological data. The integrated approach between dendrogeomorphology and geomorphological monitoring techniques allowed calibration of both tools in order to extend the analysis in the period preceding the field measurements. This kind of approach, capable of implementation in many contexts, could be particularly helpful in order to forecast the relief evolutionary trend

Structures of the lamin A/C R335W and E347K mutants: implications for dilated cardiolaminopathies

Dilated cardiomyopathy (DCM) is a condition whereby the normal muscular function of the myocardium is altered by specific or multiple aetiologies. About 25-35% of DCM patients show familial forms of the disease, with most mutations affecting genes encoding cytoskeletal proteins. Most of the DCM-related mutations fall in the Lamin AC gene, in particular in the Coil2B domain of the encoded protein. In this context, we focussed our studies on the crystal structures of two lamin Coil2B domain mutants (R335W and E347K). Both R335 and E347 are higly conserved residues whose substitution has little effects on the Coil2B domain three-dimensional structure; we can thus hypothesize that the mutations may interfere with the binding of components within the nuclear lamina, or of nuclear factors, that have been proposed to interact/associate with lamin A/C

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

Hdl in covid-19 patients: Evidence from an italian cross-sectional study

A number of studies have highlighted important alterations of the lipid profile in COVID-19 patients. Besides the well-known atheroprotective function, HDL displays anti-inflammatory, anti-oxidative, and anti-infectious properties. The aim of this retrospective study was to assess the HDL anti-inflammatory and antioxidant features, by evaluation of HDL-associated Serum amyloid A (SAA) enrichment and HDL-paraoxonase 1 (PON-1) activity, in a cohort of COVID-19 patients hospitalized at the Cardiorespiratory COVID-19 Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan. COVID-19 patients reached very low levels of HDL-c (mean ± SD: 27.1 ± 9.7 mg/dL) with a marked rise in TG (mean ± SD: 165.9 ± 62.5 mg/dL). Compared to matched-controls, SAA levels were significantly raised in COVID-19 patients at admission. There were no significant differences in the SAA amount between 83 alive and 22 dead patients for all-cause in-hospital mortality. Similar findings were reached in the case of PON-1 activity, with no differences between alive and dead patients for all-cause in-hospital mortality. In conclusion, although not related to the prediction of in-hospital mortality, reduction in HDL-c and the enrichment of SAA in HDL are a mirror of SARS-CoV-2 positivity even at the very early stages of the infection

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

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

Ivermectin reduces in vivo coronavirus infection in a mouse experimental model

SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases.Fil: Arevalo, A. P.. Instituto Pasteur de Montevideo; UruguayFil: Pagotto, R.. Instituto Pasteur de Montevideo; UruguayFil: Pórfido, Jorge Luis. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Daghero, H.. Instituto Pasteur de Montevideo; UruguayFil: Segovia, Alcira Mercedes. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Yamasaki, K.. Universidad de la Republica. Facultad de Veterinaria.; UruguayFil: Varela, B. Universidad de la Republica. Facultad de Veterinaria.; UruguayFil: Hill, Marcelo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Verdes, J. M.. Universidad de la Republica. Facultad de Veterinaria.; UruguayFil: Duhalde Vega, Maite. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Bollati Fogollin, M.. Instituto Pasteur de Montevideo; UruguayFil: Crispo, Martina. Instituto Pasteur de Montevideo; Urugua

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