Diverse reductive dehalogenases are associated with Clostridiales-enriched microcosms dechlorinating 1,2-dichloroethane

The achievement of successful biostimulation of active microbiomes for the cleanup of a polluted site is strictly dependent on the knowledge of the key microorganisms equipped with the relevant catabolic genes responsible for the degradation process. In this work, we present the characterization of the bacterial community developed in anaerobic microcosms after biostimulation with the electron donor lactate of groundwater polluted with 1,2-dichloroethane (1,2-DCA). Through a multilevel analysis, we have assessed (i) the structural analysis of the bacterial community; (ii) the identification of putative dehalorespiring bacteria; (iii) the characterization of functional genes encoding for putative 1,2-DCA reductive dehalogenases (RDs). Following the biostimulation treatment, the structure of the bacterial community underwent a notable change of the main phylotypes, with the enrichment of representatives of the order Clostridiales. Through PCR targeting conserved regions within known RD genes, four novel variants of RDs previously associated with the reductive dechlorination of 1,2-DCA were identified in the metagenome of the Clostridiales-dominated bacterial community

The cardiopulmonary exercise test in the prognostic evaluation of patients with heart failure and cardiomyopathies: the long history of making a one-size-fits-all suit

Cardiopulmonary exercise test (CPET) has become pivotal in the functional evaluation of patients with chronic heart failure (HF), supplying a holistic evaluation both in terms of exercise impairment degree and possible underlying mechanisms. Conversely, there is growing interest in investigating possible multiparametric approaches in order to improve the overall HF risk stratification. In such a context, in 2013, a group of 13 Italian centres skilled in HF management and CPET analysis built the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score, based on the dynamic assessment of HF patients and on some other instrumental and laboratory parameters. Subsequently, the MECKI score, initially developed on a cohort of 2716 HF patients, has been extensively validated as well as challenged with the other multiparametric scores, achieving optimal results. Meanwhile, the MECKI score research group has grown over time, involving up to now a total of 27 centres with an available database accounting for nearly 8000 HF patients. This exciting joint effort from multiple HF Italian centres allowed to investigate different HF research field in order to deepen the mechanisms underlying HF, to improve the ability to identify patients at the highest risk as well as to analyse particular HF categories. Most recently, some of the participants of the MECKI score group started to join the forces in investigating a possible additive role of CPET assessment in the cardiomyopathy setting too. The present study tells the ten-year history of the MECKI score presenting the most important results achieved as well as those projects in the pipeline, this exciting journey being far to be concluded

Non ST ergometric variables in the diabetic patient and their prognostic significance

Background. Recent research based on large number of patients has demonstrated that there are strong exercise predictors of cardiovascular events other than ST-segment behaviour. Studies focused on non-ST segment variables in exercise testing (exercise capacity, chronotropic and pressure response, heart rate recovery) in diabetics are lacking. The aim of our study is to find out differences in the exercise- testing variables between diabetics and non and to evaluate their prognostic role. Methods. We analyzed non ST-variables in 1172 patients undergoing exercise testing with Bruce protocol:diabetics vs non diabetics: n=83 (7%) vs n=1089 (93%); mean age: 64.37±8.44 vs 60.44±11.44; males: n=56 (67.47%) vs n=665 (61.06%). Mean follow-up was 13,5±4 months. Results. Follow-up data were available in 74 diabetics (89%), 14 (18,9%) presented cardiac events (death, infarction, coronaric revascularization, heart failure). Diabetics with events showed significantly worse 1st min Heart Rate (HR) and 3rd min Systolic Blood Pressure (SBP) recovery. Conclusions. Preliminary results highlight that non-ST variables (exercise time, chronotropic response, heart rate and blood pressure recovery) are significantly different in diabetics. Abnormal HR and SBP recovery identify a subgroup of diabetics at higher risk of cardiac events in the follow-up

Use of a 3D floating sphere culture system to maintain the neural crest-related properties of human dental pulp stem cells

Human dental pulp is considered an interesting source of adult stem cells, due to the low-invasive isolation procedures, high content of stem cells and its peculiar embryological origin from neural crest. Based on our previous findings, a dental pulp stem cells sub-population, enriched for the expression of STRO-1, c-Kit, and CD34, showed a higher neural commitment. However, their biological properties were compromised when cells were cultured in adherent standard conditions. The aim of this study was to evaluate the ability of three dimensional floating spheres to preserve embryological and biological properties of this sub-population. In addition, the expression of the inwardly rectifying potassium channel Kir4.1, Fas and FasL was investigated in 3D-sphere derived hDPSCs. Our data showed that 3D sphere-derived hDPSCs maintained their fibroblast-like morphology, preserved stemness markers expression and proliferative capability. The expression of neural crest markers and Kir4.1 was observed in undifferentiated hDPSCs, furthermore this culture system also preserved hDPSCs differentiation potential. The expression of Fas and FasL was observed in undifferentiated hDPSCs derived from sphere culture and, noteworthy, FasL was maintained even after the neurogenic commitment was reached, with a significantly higher expression compared to osteogenic and myogenic commitments. These data demonstrate that 3D sphere culture provides a favorable micro-environment for neural crest-derived hDPSCs to preserve their biological properties

A Machine Learning Approach for Mortality Prediction in COVID-19 Pneumonia: Development and Evaluation of the Piacenza Score

Background: Several models have been developed to predict mortality in patients with COVID-19 pneumonia, but only a few have demonstrated enough discriminatory capacity. Machine learning algorithms represent a novel approach for the data-driven prediction of clinical outcomes with advantages over statistical modeling.Objective: We aimed to develop a machine learning-based score-the Piacenza score-for 30-day mortality prediction in patients with COVID-19 pneumonia.Methods: The study comprised 852 patients with COVID-19 pneumonia, admitted to the Guglielmo da Saliceto Hospital in Italy from February to November 2020. Patients' medical history, demographics, and clinical data were collected using an electronic health record. The overall patient data set was randomly split into derivation and test cohorts. The score was obtained through the naive Bayes classifier and externally validated on 86 patients admitted to Centro Cardiologico Monzino (Italy) in February 2020. Using a forward-search algorithm, 6 features were identified: age, mean corpuscular hemoglobin concentration, PaO2/FiO(2) ratio, temperature, previous stroke, and gender. The Brier index was used to evaluate the ability of the machine learning model to stratify and predict the observed outcomes. A user-friendly website was designed and developed to enable fast and easy use of the tool by physicians. Regarding the customization properties of the Piacenza score, we added a tailored version of the algorithm to the website, which enables an optimized computation of the mortality risk score for a patient when some of the variables used by the Piacenza score are not available. In this case, the naive Bayes classifier is retrained over the same derivation cohort but using a different set of patient characteristics. We also compared the Piacenza score with the 4C score and with a naive Bayes algorithm with 14 features chosen a priori.Results: The Piacenza score exhibited an area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI 0.74-0.84, Brier score=0.19) in the internal validation cohort and 0.79 (95% CI 0.68-0.89, Brier score=0.16) in the external validation cohort, showing a comparable accuracy with respect to the 4C score and to the naive Bayes model with a priori chosen features; this achieved an AUC of 0.78 (95% CI 0.73-0.83, Brier score=0.26) and 0.80 (95% CI 0.75-0.86, Brier score=0.17), respectively.Conclusions: Our findings demonstrated that a customizable machine learning-based score with a purely data-driven selection of features is feasible and effective for the prediction of mortality among patients with COVID-19 pneumonia

Agerelated quantitative and qualitative changes in decision making ability

Abstract. The "frontal aging hypothesis" predicts that brain senescence affects predominantly the prefrontal regions. Preliminary evidence has recently been gathered in favour of an age-related change in a typically frontal process, i.e. decision making, using the Iowa Gambling Task (IGT), but overall findings have been conflicting. Following the traditional scoring method, coupled with a qualitative analysis, in the present study we compared IGT performance of 40 young (mean age: 27.9 ± 4.7) and 40 old (mean age: 65.4 ± 8.6) healthy adults and of 18 patients affected by frontal lobe dementia of mild severity (mean age: 65.1 ± 7.4, mean MMSE score: 24.1 ± 3.9). Quantitative findings support the notion that decision making ability declines with age; moreover, it approximates the impairment observed in executive dysfunction due to neurodegeneration. Results of the qualitative analysis did not reach statistical significance for the motivational and learning decision making components considered, but approached significance for the attentional component for elderly versus young normals, suggesting a possible decrease in the ability to maintain sustained attention during complex and prolonged tasks as the putative deficit underlying impaired decision making in normal aging

Brisk walking can be a maximal effort in heart failure patients: a comparison of cardiopulmonary exercise and 6 min walking test cardiorespiratory data

Aims Cardiopulmonary exercise test (CPET) and 6 min walking test (6MWT) are frequently used in heart failure (HF). CPET is a maximal exercise, whereas 6MWT is a self-selected constant load test usually considered a submaximal, and therefore safer, exercise, but this has not been tested previously. The aim of this study was to compare the cardiorespiratory parameters collected during CPET and 6MWT in a large group of healthy subjects and patients with HF of different severity.Methods and results Subjects performed a standard maximal CPET and a 6MWT wearing a portable device allowing breath-by-breath measurement of cardiorespiratory parameters. HF patients were grouped according to their CPET peak oxygen uptake (peak(V) over-dotO(2)). One hundred and fifty-five subjects were enrolled, of whom 40 were healthy (59 +/- 8 years; male 67%) and 115 were HF patients (69 +/- 10 years; male 80%; left ventricular ejection fraction 34.6 +/- 12.0%). CPET peak(V) over-dotO(2) was 13.5 +/- 3.5 ml/kg/min in HF patients and 28.1 +/- 7.4 mL/kg/min in healthy subjects (P < 0.001). 6MWT-(V) over-dotO(2) was 98 +/- 20% of the CPET peak(V) over-dotO(2) values in HF patients, while 72 +/- 20% in healthy subjects (P < 0.001). 6MWT-(V) over-dot was >110% of CPET peak(V) over-dotO(2) in 42% of more severe HF patients (peak(V) over-dotO(2) < 12 mL/kg/min). Similar results have been found for ventilation and heart rate. Of note, the slope of the relationship between (V) over-dotO(2) at 6MWT, reported as a percentage of CPET peak(V) over-dotO(2) vs. 6MWT (V) over-dotO(2) reported as the absolute value, progressively increased as exercise limitation did.Conclusions In conclusion, the last minute of 6MWT must be perceived as a maximal or even supramaximal exercise activity in patients with more severe HF. Our findings should influence the safety procedures needed for the 6MWT in HF

Reference Values for Peak Exercise Cardiac Output in Healthy Individuals

BACKGROUND: Cardiac output (Q\u2d9) is a key parameter in the assessment of cardiac function, its measurement being crucial for the diagnosis, treatment, and prognostic evaluation of all heart diseases. Until recently, Q\u2d9 determination at peak exercise has been possible through invasive methods, so that normal values were obtained in studies based on small populations. METHODS: Nowadays, peak Q\u2d9 can be measured noninvasively by means of the inert gas rebreathing (IGR) technique. The present study was undertaken to provide reference values for peak Q\u2d9 in the normal general population and to obtain a formula able to estimate peak exercise Q\u2d9 from measured peak oxygen uptake (V\u2d9o2). RESULTS: We studied 500 normal subjects (age, 44.9 \ub1 1.5 years; range, 18-77 years; 260 men, 240 women) who underwent a maximal cardiopulmonary exercise test with peak Q\u2d9 measurement by IGR. In the overall study sample, peak Q\u2d9 was 13.2 \ub1 3.5 L/min (men, 15.3 \ub1 3.3 L/min; women, 11.0 \ub1 2.0 L/min; P < .001) and peak V\u2d9o2 was 95% \ub1 18% of the maximum predicted value (men, 95% \ub1 19%; women, 95% \ub1 18%). Peak V\u2d9o2 and peak Q\u2d9 progressively decreased with age (R2, 0.082; P < .001; and R2, 0.144; P < .001, respectively). The V\u2d9o2-derived formula to measure Q\u2d9 at peak exercise was (4.4 7 peak V\u2d9o2) + 4.3 in the overall study cohort, (4.3 7 peak V\u2d9o2) + 4.5 in men, and (4.9 7 peak V\u2d9o2) + 3.6 in women. CONCLUSIONS: The simultaneous measurement of Q\u2d9 and V\u2d9o2 at peak exercise in a large sample of healthy subjects provided an equation to predict peak Q\u2d9 from peak V\u2d9o2 values

Surface Quality Improvement of AA6060 Aluminum Extruded Components through Liquid Nitrogen Mold Cooling

6xxx aluminum alloys are suitable for the realization of both structural applications and architectural decorative elements, thanks to the combination of high corrosion resistance and good surface finish. In areas where the aesthetic aspects are fundamental, further improvements in surface quality are significant. The cooling of the extrusion mold via internal liquid nitrogen fluxes is emerging as an important innovation in aluminum extrusion. Nowadays, this innovation is providing a large-scale solution to obtain high quality surface finishes in extruded aluminum semi-finished products. These results are also coupled to a significant increase in productivity. The aim of the work is to compare the surface quality of both cooled liquid nitrogen molds and classically extruded products. In this work, adhesion phenomena, occurring during the extrusion between the mold and the flowing material, have been detected as the main causes of the presence of surface defects. The analysis also highlighted a strong increase in the surface quality whenever the extrusion mold was cooled with liquid nitrogen fluxes. This improvement has further been confirmed by an analysis performed on the finished products, after painting and chromium plating. This work on the AA6060 alloy has moreover proceeded to roughness measurements and metallographic analyses, to investigate the eventual occurrence of other possible benefits stemming from this new extrusion mold cooling technology

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score

Background: Long -term consequences of COVID-19 are still partly known. Aim of the study: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. Methods: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the CardioCovid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. Results: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60 +/- 16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1 -4 points for age class ( = 85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups ( 6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). Conclusions: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up