Blood baseline values in female alpine and nera di verzasca goats reared in italy.

The Italian goat autochthonous breeds are appreciated for their milk and characteristics, especially for the rusticity, frugality, fertility and longevity. For these reasons the local goat breeds play an important role in the livestock sector, and it is important to guarantee sanitary strategies control, prevention or treatment of diseases. It is well known that the hematological parameters in goats undergo changes in relation with many factors like breed, age (Piccione et al. 2014), physiological/reproductive status environmental factors and stress (Waziri M.A. et al. 2010).  Based on these differences it is necessary to establish appropriate physiological baseline values for every single breed which could be used in the realistic evaluation physiological or pathological status of the animal (Arfuso et al. 2016). The aim of this work was to evaluate the differences between a local goat breed (Verzasca) and a cosmopolite one (Alpine) from the hematological point of view, and to establish hematological reference values. A total number of 71 female goats, of Alpine (n=37), and Verzasca (n=34) were enrolled for this study, for a total of 716 blood samples. Data were processed by a mixed model-repeated measures ANCOVA in order to evaluate the effects of breed, parity, and season, while baseline values for each breed have been calculated by evaluating the 2.5-97.5th  percentile of variables distribution.The results showed that the breeds differ in a significant manner (Table 1). Verzasca goat shows significantly higher values in the erythroid parameters, whereas the Alpine goat shows higher mean values of leucocyte count and absolute neutrophil count. A further interesting result is the neutrophil lymphocyte ratio which is 0.96  in the Alpine and 0,57 in the Verzasca.The results here presented can add some knowledge to the definition of the health status of the two breeds, evidencing some environmental and physiological variation mechanisms.

New bioelectrical impedance vector references and phase angle centile curves in 4,367 adults: The need for an urgent update after 30 years

Background & aims: The bioelectrical impedance vector analysis (BIVA) represents a qualitative analysis of body composition. The vector, defined by resistance (R) and reactance (Xc) standardized by stature, can be evaluated compared to the 50%,75%, and 95% tolerance ellipses representative of the reference populations. The tolerance ellipses for healthy adults have been provided in 1995 and were developed by mixing underage, adult, and elderly subjects, possibly misrepresenting the actual adult population. The current multicentric, cross-sectional study aimed to provide new tolerance ellipses specific for the general adult population and as a secondary aim to present centile curves for the bioelectrical phase angle. Methods: R, Xc, and phase angle were measured in 2137 and 2230 males and females using phase-sensitive foot-to-hand analyzers at 50 kHz. A minimum of 35 subjects were included for each sex and age category from 18 to 65 years. Results: The new mean vectors showed a leftward shift on the R-Xc graph with respect to the former reference values (males: F = 75.3; p < 0.001; females: F = 36.6, p < 0.001). The results provided new 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 97th percentile curves for phase angle, identifying time point phases of decrement (males: -0.03° per year at 33.0-51.0 years and -0.05° per year after 51 years; females: -0.03° per year from 37.2 to 57.9 years). Conclusions: Compared to the original references, the new data are characterized by a different distribution within the R-Xc graph with a higher phase angle. Thirty years after the BIVA invention, the current study presents new tolerance ellipses and phase angle reference values for the adult population

Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands

Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP-regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP-competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2-phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 æ from the active site. Specifically, analysis of protein responses to first-generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules’ effects on Hsp90 enzymatic, conformational, cochaperone and client-binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary

A Machine-Learning Approach to Target Clinical and Biological Features Associated with Sarcopenia: Findings from Northern and Southern Italian Aging Populations

Epidemiological and public health resonance of sarcopenia in late life requires further research to identify better clinical markers useful for seeking proper care strategies in preventive medicine settings. Using a machine-learning approach, a search for clinical and fluid markers most associated with sarcopenia was carried out across older populations from northern and southern Italy. A dataset of adults >65 years of age (n = 1971) made up of clinical records and fluid markers from either a clinical-based subset from northern Italy (Pavia) and a population-based subset from southern Italy (Apulia) was employed (n = 1312 and n = 659, respectively). Body composition data obtained by dual-energy X-ray absorptiometry (DXA) were used for the diagnosis of sarcopenia, given by the presence of either low muscle mass (i.e., an SMI 2 for males or 2 for females) and of low muscle strength (i.e., an HGS < 27 kg for males or <16 kg for females) or low physical performance (i.e., an SPPB ≤ 8), according to the EWGSOP2 panel guidelines. A machine-learning feature-selection approach, the random forest (RF), was used to identify the most predictive features of sarcopenia in the whole dataset, considering every possible interaction among variables and taking into account nonlinear relationships that classical models could not evaluate. Then, a logistic regression was performed for comparative purposes. Leading variables of association to sarcopenia overlapped in the two population subsets and included SMI, HGS, FFM of legs and arms, and sex. Using parametric and nonparametric whole-sample analysis to investigate the clinical variables and biological markers most associated with sarcopenia, we found that albumin, CRP, folate, and age ranked high according to RF selection, while sex, folate, and vitamin D were the most relevant according to logistics. Albumin, CRP, vitamin D, and serum folate should not be neglected in screening for sarcopenia in the aging population. Better preventive medicine settings in geriatrics are urgently needed to lessen the impact of sarcopenia on the general health, quality of life, and medical care delivery of the aging population

New genes and pathomechanisms in mitochondrial disorders unraveled by NGS technologies.

Next Generation Sequencing (NGS) technologies are revolutionizing the diagnostic screening for rare disease entities, including primary mitochondrial disorders, particularly those caused by nuclear gene defects. NGS approaches are able to identify the causative gene defects in small families and even single individuals, unsuitable for investigation by traditional linkage analysis. These technologies are contributing to fill the gap between mitochondrial disease cases defined on the basis of clinical, neuroimaging and biochemical readouts, which still outnumber by approximately 50% the cases for which a molecular-genetic diagnosis is attained. We have been using a combined, two-step strategy, based on targeted genes panel as a first NGS screening, followed by whole exome sequencing (WES) in still unsolved cases, to analyze a large cohort of subjects, that failed to show mutations in mtDNA and in ad hoc sets of specific nuclear genes, sequenced by the Sanger's method. Not only this approach has allowed us to reach molecular diagnosis in a significant fraction (20%) of these difficult cases, but it has also revealed unexpected and conceptually new findings. These include the possibility of marked variable penetrance of recessive mutations, the identification of large-scale DNA rearrangements, which explain spuriously heterozygous cases, and the association of mutations in known genes with unusual, previously unreported clinical phenotypes. Importantly, WES on selected cases has unraveled the presence of pathogenic mutations in genes encoding non-mitochondrial proteins (e.g. the transcription factor E4F1), an observation that further expands the intricate genetics of mitochondrial disease and suggests a new area of investigation in mitochondrial medicine. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi

Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis.

Biallelic mutations in NDUFAF6 have been identified as responsible for cases of autosomal recessive Leigh syndrome associated with mitochondrial complex I deficiency. Here we report two siblings and two unrelated subjects with Leigh syndrome, in which we found the same compound heterozygous missense (c.532G>C:p.A178P) and deep intronic (c.420+784C>T) variants in NDUFAF6. We demonstrated that the identified intronic variant creates an alternative splice site, leading to the production of an aberrant transcript. A detailed analysis of whole-exome sequencing data together with the functional validation based on mRNA analysis may reveal pathogenic variants even in non-exonic regions

Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy

none140noNAnoneColaneri M.; Seminari E.; Piralla A.; Zuccaro V.; Di Filippo A.; Baldanti F.; Bruno R.; Mondelli M.U.; Brunetti E.; Di Matteo A.; Maiocchi L.; Pagnucco L.; Mariani B.; Ludovisi S.; Lissandrin R.; Parisi A.; Sacchi P.; Patruno S.F.A.; Michelone G.; Gulminetti R.; Zanaboni D.; Novati S.; Maserati R.; Orsolini P.; Vecchia M.; Sciarra M.; Asperges E.; Sambo M.; Biscarini S.; Lupi M.; Roda S.; Chiara Pieri T.; Gallazzi I.; Sachs M.; Valsecchi P.; Perlini S.; Alfano C.; Bonzano M.; Briganti F.; Crescenzi G.; Giulia Falchi A.; Guarnone R.; Guglielmana B.; Maggi E.; Martino I.; Pettenazza P.; Pioli di Marco S.; Quaglia F.; Sabena A.; Salinaro F.; Speciale F.; Zunino I.; De Lorenzo M.; Secco G.; Dimitry L.; Cappa G.; Maisak I.; Chiodi B.; Sciarrini M.; Barcella B.; Resta F.; Moroni L.; Vezzoni G.; Scattaglia L.; Boscolo E.; Zattera C.; Michele Fidel T.; Vincenzo C.; Vignaroli D.; Bazzini M.; Iotti G.; Mojoli F.; Belliato M.; Perotti L.; Mongodi S.; Tavazzi G.; Marseglia G.; Licari A.; Brambilla I.; Daniela B.; Antonella B.; Patrizia C.; Giulia C.; Giuditta C.; Marta C.; Rossana D.; Milena F.; Bianca M.; Roberta M.; Enza M.; Stefania P.; Maurizio P.; Elena P.; Antonio P.; Francesca R.; Antonella S.; Maurizio Z.; Guy A.; Laura B.; Ermanna C.; Giuliana C.; Luca D.; Gabriella F.; Gabriella G.; Alessia G.; Viviana L.; Claudia L.; Valentina M.; Simona P.; Marta P.; Alice B.; Giacomo C.; Irene C.; Alfonso C.; Di Martino R.; Di Napoli A.; Alessandro F.; Guglielmo F.; Loretta F.; Federica G.; Alessandra M.; Federica N.; Giacomo R.; Beatrice R.; Maria S.I.; Monica T.; Nepita Edoardo V.; Calvi M.; Tizzoni M.; Nicora C.; Triarico A.; Petronella V.; Marena C.; Muzzi A.; Lago P.; Comandatore F.; Bissignandi G.; Gaiarsa S.; Rettani M.; Bandi C.Colaneri, M.; Seminari, E.; Piralla, A.; Zuccaro, V.; Di Filippo, A.; Baldanti, F.; Bruno, R.; Mondelli, M. U.; Brunetti, E.; Di Matteo, A.; Maiocchi, L.; Pagnucco, L.; Mariani, B.; Ludovisi, S.; Lissandrin, R.; Parisi, A.; Sacchi, P.; Patruno, S. F. A.; Michelone, G.; Gulminetti, R.; Zanaboni, D.; Novati, S.; Maserati, R.; Orsolini, P.; Vecchia, M.; Sciarra, M.; Asperges, E.; Sambo, M.; Biscarini, S.; Lupi, M.; Roda, S.; Chiara Pieri, T.; Gallazzi, I.; Sachs, M.; Valsecchi, P.; Perlini, S.; Alfano, C.; Bonzano, M.; Briganti, F.; Crescenzi, G.; Giulia Falchi, A.; Guarnone, R.; Guglielmana, B.; Maggi, E.; Martino, I.; Pettenazza, P.; Pioli di Marco, S.; Quaglia, F.; Sabena, A.; Salinaro, F.; Speciale, F.; Zunino, I.; De Lorenzo, M.; Secco, G.; Dimitry, L.; Cappa, G.; Maisak, I.; Chiodi, B.; Sciarrini, M.; Barcella, B.; Resta, F.; Moroni, L.; Vezzoni, G.; Scattaglia, L.; Boscolo, E.; Zattera, C.; Michele Fidel, T.; Vincenzo, C.; Vignaroli, D.; Bazzini, M.; Iotti, G.; Mojoli, F.; Belliato, M.; Perotti, L.; Mongodi, S.; Tavazzi, G.; Marseglia, G.; Licari, A.; Brambilla, I.; Daniela, B.; Antonella, B.; Patrizia, C.; Giulia, C.; Giuditta, C.; Marta, C.; D'Alterio, Rossana; Milena, F.; Bianca, M.; Roberta, M.; Enza, M.; Stefania, P.; Maurizio, P.; Elena, P.; Antonio, P.; Francesca, R.; Antonella, S.; Maurizio, Z.; Guy, A.; Laura, B.; Ermanna, C.; Giuliana, C.; Luca, D.; Gabriella, F.; Gabriella, G.; Alessia, G.; Viviana, L.; Meisina, Claudia; Valentina, M.; Simona, P.; Marta, P.; Alice, B.; Giacomo, C.; Irene, C.; Alfonso, C.; Di Martino, R.; Di Napoli, A.; Alessandro, F.; Guglielmo, F.; Loretta, F.; Federica, G.; Albertini, Alessandra; Federica, N.; Giacomo, R.; Beatrice, R.; Maria, S. I.; Monica, T.; Nepita Edoardo, V.; Calvi, M.; Tizzoni, M.; Nicora, C.; Triarico, A.; Petronella, V.; Marena, C.; Muzzi, A.; Lago, P.; Comandatore, F.; Bissignandi, G.; Gaiarsa, S.; Rettani, M.; Bandi, C

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21\u201328 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age&gt;65 years, antiviral treatment and for severe disease, lactate dehydrogenase &gt;300 mg/dL

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio