Subcellular localization of the five members of the human steroid 5α-reductase family

In humans the steroid 5a-reductase (SRD5A) family comprises five integral membrane enzymes that carry out reduction of a double bond in lipidic substrates: D4-3-keto steroids, polyprenol and trans-enoyl CoA. The best-characterized reaction is the conversion of testosterone into the more potent dihydrotestosterone carried out by SRD5A1-2. Some controversy exists on their possible nuclear or endoplasmic reticulum localization. We report the cloning and transient expression in HeLa cells of the five members of the human steroid 5a-reductase family as both N- and Cterminus green fluorescent protein tagged protein constructs. Following the intrinsic fluorescence of the tag, we have determined that the subcellular localization of these enzymes is in the endoplasmic reticulum, upon expression in HeLa cells. The presence of the tag at either end of the polypeptide chain can affect protein expression and, in the case of trans enoyl-CoA reductase, it induces the formation of protein aggregates

May-Hegglin Anomaly, Sebastian Syndrome, Fechtner Syndrome, and Epstein Syndrome Are not Distinct Entities but Represent a Variable Expression of a Single Illness

May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without Döhle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term "MHY9-related disease," which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects

Reliability of Lupus Anticoagulant and Anti-phosphatidylserine/prothrombin Autoantibodies in Antiphospholipid Syndrome: A Multicenter Study

Background: Is it well-known that one of the major drawbacks of Lupus Anticoagulant (LA) test is their sensitivity to anticoagulant therapy, due to the coagulation based principle. In this study we aimed to assess the reproducibility of LA testing and to evaluate the performance of solid assay phosphatidylserine/prothrombin (aPS/PT) antibodies.Methods: We included 60 patients that fulfilled the following inclusion criteria: (I) diagnosis of thrombotic antiphospholipid syndrome (APS); (II) patients with thrombosis and (a) inconstant previous LA positivity and/or (b) positivity for antiphospholipid antibodies (aPL) at low-medium titers [defined as levels of anti-β2Glycoprotein-I or anticardiolipin (IgG/IgM) 10–30 GPL/MPL] with no previous evidence of LA positivity. aPL testing was performed blindly in 4 centers undertaking periodic external quality assessment.Results: The 60 patients enrolled were distributed as follows: 43 (71.7%) with thrombotic APS, 7 (11.7%) with thrombosis and inconstant LA positivity and 10 (16.7%) with low-medium aPL titers. Categorical agreement for LA among the centers ranged from 0.41 to 0.60 (Cohen's kappa coefficient; moderate agreement). The correlation determined at the 4 sites for aPS/PT was strong, both quantitatively (Spearman rho 0.84) and when dichotomized (Cohen's kappa coefficients = 0.81 to 1.0). Discordant (as defined by lack of agreement in ≥3 laboratories) or inconclusive LA results were observed in 27/60 (45%) cases; when limiting the analysis to those receiving vitamin K antagonist (VKA), the level of discordant LA results was as high as 75%(15/20). Conversely, aPS/PT testing showed an overall agreement of 83% (up to 90% in patients receiving VKA), providing an overall increase in test reproducibility of +28% when compared to LA, becoming even more evident (+65%) when analyzing patients on VKA. In patients treated with VKA, we observed a good correlation for aPS/PT IgG testing (Cohen's kappa coefficients = 0.81–1; Spearman rho 0.86).Conclusion: Despite the progress in the standardization of aPL testing, we observed up to 45% of overall discrepant results for LA, even higher in patients on VKA. The introduction of aPS/PT testing might represent a further diagnostic tool, especially when LA testing is not available or the results are uncertain

Pediatric admissions to emergency departments of North-Western Italy during COVID-19 pandemic: A retrospective observational study

COVID-19 pandemic caused huge decrease of pediatric admissions to Emergency Department (ED), arising concerns about possible delays in diagnosis and treatment of severe disorders

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. Methods/design The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. Discussion To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. Trial registration ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1929-0) contains supplementary material, which is available to authorized users

Università e Città. Introduzione al tema monografico University and City. Introduction to the Special Issue

Il saggio presenta il tema della Città Universitaria come fattore strategico di sviluppo territoriale, con riferimento alle attività di ricerca del Laboratorio UNICITY sulle relazioni tra Città e Unviersità di Padov

La costruzione di nuove forme di relazione istituzionale tra Università e Città. Padova, Unicitylab e Urban center

UNICITYLAB (2019-2022) presso l’Università di Padova è stata un’interessante esperienza triennale di cooperazione interdipartimentale e interdisciplinare che ha cercato di studiare e analizzare le forme e gli effetti della presenza di un Ateneo pluricentenario in una città di medie dimensioni. Non si è trattato solo di un lavoro di analisi critica di un contesto complesso, ma piuttosto dell’esplorazione dei processi in atto, delle reti istituzionali e non, in cui provare ad avanzare proposte di un’azione diversa, innovativa e incisiva dell’università nella realtà padovana. La costituzione di un nuovo luogo di confronto, collaborazione e co-progettazione, che in modo semplificato chiamiamo “Urban Center”, sembra al momento la via concordata per una collaborazione tra Università e Amministrazione comunale a Padova, dove provare in primo luogo a costruire la “rete” di attori sociali con cui definire strategie di medio lungo periodo per “lo sviluppo, potenziamento e miglioramento della città universitaria” e cercare di rispondere ad immediate emergenze

New Forms of Relationships Between the University and the City: Padua, the UnicityLab Project, and the Idea of an Urban Center

UNICITYLab (2019-2022) has been an interesting three-year experience of interdepartmental and interdisciplinary cooperation taking place at the University of Padua, which sought to study and analyse the forms and effects of the presence of a pluricentennial university in a medium-sized city. The UNICITYLab activities – beyond the exploration of the characteristics and conditions of the context –have been devoted to a crucial examination of the relationships between the two chief institutions in the City and their mutual policies to cope with emerging problems. It results in a lack of information about processes in progress or institutional and non-institutional networks; a general misunderstanding about issues to manage; no awareness about the need of cooperation. UNICITYLab has worked to present evidence of the situation and the need to put forward proposals for an innovative and incisive action, with the definition of a different role from the past, proactive, open, and collaborative, in the system of local relations. The organisation of a new place for discussion, collaboration, and co-planning, which we call the “Urban Centre” in a simplified way, currently seems to be a feasible solution