University of Milan

Not all governments survive until the next scheduled election. Some are replaced during their term in office by executives with a different party composition and/or portfolio distribution. Others are able to be ‘reborn’ as the successor government, undergoing only minimal changes. Such variation has to date received scant attention in studies on government durability. By classifying non-electoral replacements according to the degree of ministerial turnover, this article shows that new cabinets are often similar to their predecessors. It hypothesises that the likelihood of this pattern occurring is greater: when members of the current cabinet face bargaining problems in forming a very different cabinet, as in the case of surplus (unnecessary) parties in oversized coalitions; when the policy distance between the parliamentary median party and the current opposition widens; and when the executive’s economic performance discourages opposition parties from forming new coalitions with some incumbent parties. The risk of experiencing different types of replacement is estimated using data on Western European cabinets (1946–2021). Consistent with the hypotheses, the results indicate that governments are able to return to power almost untouched after their termination if they are oversized, if the opposition is far from the legislative median voter, and if inflation grows during a government’s tenure.

Introduction Submaximal strength testing appears to be valid to prescribe the intensity for strength training protocols that reduce the risk of injuries and testing time. Objective This study aimed to assess the predictive ability of body mass parameters to estimate 4-6 repetitions maximum (4-6 RM) of Leg press 45°, Chest press, and Pull-down exercises. Methods Eleven male bodybuilders (age 38.27 ± 10.48 years) participated in this study. Participants completed an incremental external load up to find the load allowing them to perform 4 to 6 maximal repetitions for each exercise in random order. The starting load was 50% of body mass for chest press and pull-down exercises and 100% for leg press. The load increment after each set was 20 kg for lower limb exercises and 10 kg for upper body exercises. Results Results revealed that body mass had good to optimal relationships with 4-6 RM for all three exercises. Results showed that body mass had a good prediction ability for all three criterion measures. Conclusion The prediction equations suggested in this study may allow coaches to estimate the 4-6 RM of leg press 45°, chest press, and pull-down performances. Evidence Level IV; Case series. Keywords: Predictions and Projections; Muscle Strength; Body Weight

The gut microbiota is believed to be a critical factor in the pathogenesis of IBS, and its metabolic byproducts, such as short-chain fatty acids (SCFAs), are known to influence gut function and host health. Despite this, the precise role of SCFAs in IBS remains a topic of debate. In this study, we examined the bacterial community structure by 16S rRNA gene profiling and SCFA levels by UPLC-MS/MS in fecal samples from healthy controls (HC; n = 100) and non-constipated patients (IBS-D and IBS-M; NC-IBS; n = 240) enrolled in 19 hospitals in Italy. Our findings suggest a significant difference between the fecal microbiomes of NC-IBS patients and HC subjects, with HC exhibiting higher intra-sample biodiversity. Furthermore, we were able to classify non-constipated patients into two distinct subgroups based on their fecal SCFA levels (fecal catabotype "high" and "low"), each characterized by unique taxonomic bacterial signatures. Our results suggest that the fecal catabotype with higher SCFA levels may represent a distinct clinical phenotype of IBS that could have implications for its diagnosis and treatment. This study provides a new perspective on the intricate relationship between the gut microbiome and bowel symptoms in IBS, underscoring the importance of personalized strategies for its management.

Purpose/background: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. Methods/procedures: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. Findings/results: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. Implications/conclusions: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.

Rationale: Although inflammation and infection are key disease drivers in bronchiectasis, few studies have integrated host inflammatory and microbiome data to guide precision medicine. Objectives: To identify clusters among bronchiectasis patients based on inflammatory markers and assess the association between inflammatory endotypes, microbiome characteristics, and exacerbation risk. Methods: Stable bronchiectasis patients were enrolled at three European centers and cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Clusters were compared in terms of microbiome composition (16S rRNA sequencing) and exacerbation risk over 12 months follow-up. Measurements and main results: 199 patients were enrolled (109 [54.8%] female, median age 69 years). Four clusters of patients were defined according to their inflammatory profiles: cluster 1 (milder neutrophilic inflammation), cluster 2 (mixed-neutrophilic and type 2), cluster 3 (most severe neutrophilic), and cluster 4 (mixed-epithelial and type 2). Lower microbiome diversity was associated with more severe inflammatory clusters (P<0.001), and beta-diversity analysis demonstrated distinct microbiome profiles associated with each inflammatory cluster (P=0.001). Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more enriched in clusters 2 and 3 than in clusters 1 and 4. Furthermore, patients in clusters 2 (rate ratio [RR] 1.49, 95% CI 1.16-1.92) and 3 (RR 1.61, 95% CI 1.12-2.32) were at higher risk of exacerbation over 12 months follow-up compared to cluster 1 even after adjustment for prior exacerbation history. Conclusion: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.

The phosphorescence of boric acid (BA, H 3 BO 3) at room temperature is a puzzling phenomenon subject to controversial interpretations although the role of structural defects has not yet been considered. Heat treatments of boric acid cause its transformation into the metaboric phase and amorphous boron oxide (B 2 O 3). The structural changes after thermal processing can create defects that become centers of luminescence and recombination channels in the visible range. In the present work, commercial boric acid is thermally processed at different temperatures. Samples treated between 200 and 400°C exhibit remarkable phosphorescence in the visible range. At ≈480 and 528 nm, two distinct phosphorescent emissions occur, associated with trapped charge carriers recombinations identified by thermoluminescence (TL) and electron paramagnetic resonance spectroscopy (EPR). The structural and optical studies suggest that the activation of boric acid phosphorescence after heat treatment is correlated with the presence of defects. The afterglow results from a trapping and detrapping process, which delays the recombination at the active optical centers. Time-dependent density functional study (DFT) of defective BOH molecules and clusters shows the emergence of near UV and blue optical transitions in absorption. These defects trigger the photoluminescence in thermally processed boric acid samples.

BACKGROUND Cholesterol efflux capacity (CEC) predicts cardiovascular disease independently of high-density lipoprotein (HDL) cholesterol levels. Isolated small HDL particles are potent promoters of macrophage CEC by the ABCA1 (ATP-binding cassette transporter A1) pathway, but the underlying mechanisms are unclear. METHODS We used model system studies of reconstituted HDL and plasma from control and lecithin-cholesterol acyltransferase (LCAT)–deficient subjects to investigate the relationships among the sizes of HDL particles, the structure of apoA1 (apolipoprotein A1) in the different particles, and the CECs of plasma and isolated HDLs. RESULTS We quantified macrophage and ABCA1 CEC of 4 distinct sizes of reconstituted HDL. CEC increased as particle size decreased. Tandem mass spectrometry analysis of chemically cross-linked peptides and molecular dynamics simulations of apoA1, the major protein of HDL, indicated that the mobility of C-terminus of that protein was markedly higher and flipped off the surface in the smallest particles. To explore the physiological relevance of the model system studies, we isolated HDL from LCAT-deficient subjects, the small HDLs (eg, reconstituted HDLs) of which are discoidal and composed of apoA1, cholesterol, and phospholipid. Despite their very low plasma levels of HDL particles, these subjects had normal CEC. In both the LCAT-deficient subjects and control subjects, the CEC of isolated extra-small HDL (a mixture of extra-small and small HDL by calibrated ion mobility analysis) was 3- to 5-fold greater than that of the larger sizes of isolated HDL. Incubating LCAT-deficient plasma and control plasma with human LCAT converted extra-small and small HDL particles into larger particles, and it markedly inhibited CEC. CONCLUSIONS We present a mechanism for the enhanced CEC of small HDLs. In smaller particles, the C-termini of the 2 antiparallel molecules of apoA1 are “flipped” off the lipid surface of HDL. This extended conformation allows them to engage with ABCA1. In contrast, the C-termini of larger HDLs are unable to interact productively with ABCA1 because they form a helical bundle that strongly adheres to the lipid on the particle. Enhanced CEC, as seen with the smaller particles, predicts decreased cardiovascular disease risk. Thus, extra-small and small HDLs may be key mediators and indicators of the cardioprotective effects of HDL.

The development of virtual care options, including virtual hospital platforms, is rapidly changing the healthcare, mostly in the pandemic period, due to difficulties in in-person consultations. For this purpose, in 2020, a neurological Virtual Hospital (NOVHO) pilot study has been implemented, in order to experiment a multidisciplinary second opinion evaluation system for neurological diseases. Cerebrovascular diseases represent a preponderant part of neurological disorders. However, more than 30% of strokes remain of undetermined source, and rare CVD (rCVD) are often misdiagnosed. The lack of data on phenotype and clinical course of rCVD patients makes the diagnosis and the development of therapies challenging. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, their management is mostly allocated to a few experienced hospitals, making difficult equity in access to care. Therefore, strategies for virtual consultations are increasingly applied with some advantage for patient management also in peripheral areas. Moreover, health data are becoming increasingly complex and require new technologies to be managed. The use of Artificial Intelligence is beginning to be applied to the healthcare system and together with the Internet of Things will enable the creation of virtual models with predictive abilities, bringing healthcare one step closer to personalized medicine. Herein, we will report on the preliminary results of the NOVHO project and present the methodology of a new project aimed at developing an innovative multidisciplinary and multicentre virtual care model, specific for rCVD (NOVHO-rCVD), which combines the virtual hospital approach and the deep-learning machine system.

During the last years, many new technologies, like laparoscopy, endoscopy, and robotics, have been introduced in surgery to improve daily practice. Among these techniques, “fluorescence-guided surgery” (FGS) is an intraoperative imaging system allowing the identification of structures through fluorescent probes and dedicated technology. The main aim is to improve surgical guidance. This chapter will discuss the history of immunofluorescence, basic principles of fluorescence, fluorescent probes in surgery, and clinical imaging systems. Since its first clinical application in the surgical field in 1947, fluorescence has undergone a huge development and diffusion. To date, fluorescence has several applications in every surgical specialty like perfusion assessment, cholangiography, lymphography, tumor identification, and ureter identification. The technique implies the administration of a fluorescent probe that is excited by light excitation source and emitted by dedicated instruments, with consequent emission of a fluorescent signal that is detected and visualized on a screen. Among the fluorescent probes already approved for clinical use, like methylene blue, fluorescein sodium, and 5-aminolevulinic acid, the most diffused is indocyanine green (ICG). ICG has some peculiar features that promote its widespread use: it is virtually harmless, due to the lowest rate of adverse effects reported and to the very high toxic dose for the human body, and it is not expensive. Many probes are currently under clinical development and will be on the market soon. A growing number of companies developed new systems for FGS with excitation and emission spectra in the nearinfrared wavelength range, which are suitable for both fluorescence and white light imaging.

Human Resource Management research is striving to develop rigorous and actionable knowledge for today’s social and environmental global challenges. For years, academic‐stakeholder collaborative knowledge creation processes have been considered as potentially rewarding ways to achieve this objective. However, applications of collaborative HRM research are still relatively sparse, as HR scholars tend to engage with more traditional processes of knowledge creation. The aim of this editorial is to foster more widespread conduct of collaborative HRM research in the future. Drawing on Habermas, whose ideas on human knowledge are considered to be at the core of the epistemology of collaborative management research, we first highlight three avenues for collaborative HRM research that addresses our technical, practical and emancipatory knowledge‐constitutive interests. For each of them, we highlight key theoretical assumptions and risks. Thereafter, we describe two key requirements for rigour and relevance in the context of any collaborative HRM study. Finally, we present the papers included in this special section and discuss their implications for HRM research.

Manual dexterity is a key skill in motor development. There are conflicting studies on the influence of sports practice on this skill and on which type of sport trains this ability the most in youth. Manual dexterity is usually assessed with expensive and time-consuming tools not easily available to facilities such as schools or sports clubs. The aim of this study was to assess differences in manual dexterity performance between young basketball players, sportsmen, and non-sportsmen. A further aim was to analyze whether the coin rotation task was a reliable tool for assessing manual dexterity. Based on the characteristics of the sport, we hypothesized that basketball players had better manual dexterity performances. Seventy-eight participants were included in the study and categorized into “basketball”, “sports”, and “non-sports” groups. Manual dexterity was assessed with the grooved pegboard, the coin rotation task, and the handgrip tests. The basketball group showed better performance in all tests. Significant differences were found between the basketball group and sports group and between the basketball group and non-sport group in the grooved pegboard (p < 0.05) and in the handgrip (p < 0.05) tests. Test–retest reliability of the coin rotation task scores was moderate in the basketball group (ICC2,1 0.63–0.6). Basketball practice could positively influence manual dexterity. The coin rotation task showed an acceptable construct of validity.

Background Matrix metalloproteinase 12 (MMP12) is a macrophage-secreted protein that is massively upregulated as a pro-inflammatory factor in metabolic and vascular tissues of mice and humans suffering from cardiometabolic diseases (CMDs). However, the molecular mechanisms explaining the contributions of MMP12 to CMDs are still unclear. Methods We investigated the impact of MMP12 deficiency on CMDs in a mouse model that mimics human disease by simultaneously developing adipose tissue inflammation, insulin resistance, and atherosclerosis. To this end, we generated and characterized low-density lipoprotein receptor (Ldlr)/Mmp12-double knockout (DKO) mice fed a high-fat sucrose- and cholesterol-enriched diet for 16–20 weeks. Results DKO mice showed lower cholesterol and plasma glucose concentrations and improved insulin sensitivity compared with LdlrKO mice. Untargeted proteomic analyses of epididymal white adipose tissue revealed that inflammation- and fibrosis-related pathways were downregulated in DKO mice. In addition, genetic deletion of MMP12 led to alterations in immune cell composition and a reduction in plasma monocyte chemoattractant protein-1 in peripheral blood which indicated decreased low-grade systemic inflammation. Aortic en face analyses and staining of aortic valve sections demonstrated reduced atherosclerotic plaque size and collagen content, which was paralleled by an improved relaxation pattern and endothelial function of the aortic rings and more elastic aortic sections in DKO compared to LdlrKO mice. Shotgun proteomics revealed upregulation of anti-inflammatory and atheroprotective markers in the aortas of DKO mice, further supporting our data. In humans, MMP12 serum concentrations were only weakly associated with clinical and laboratory indicators of CMDs. Conclusion We conclude that the genetic deletion of MMP12 ameliorates obesity-induced low-grade inflammation, white adipose tissue dysfunction, biomechanical properties of the aorta, and the development of atherosclerosis. Therefore, therapeutic strategies targeting MMP12 may represent a promising approach to combat CMDs.

Introduction: Impairment of the gastrointestinal (GI) barrier leads to microbial translocation and peripheral immune activation which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely- and chronically-infected, combination cART-naïve individuals. Methods: Fifteen people with Primary HIV infection (P-HIV) and 13 with Chronic HIV infection (C-HIV) c-ART naïve participants were cross-sectionally studied. Gut biopsies were analyzed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4 expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3+panγδ+Vδ1+/Vδ2+). In plasma we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA). Results: P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared to C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV. Conclusions: Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely due to a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells.

Purpose To assess whether 5‐year overall survival (OS) of squamous cell carcinoma of the penis (SCCP) patients differs from age‐matched male population‐based controls. Methods We relied on the Surveillance Epidemiology and End Results database (2004–2018) to identify newly diagnosed (2004–2013) SCCP patients. For each case, we simulated an age‐matched control (Monte Carlo simulation), relying on the Social Security Administration (SSA) Life Tables with 5 years of follow‐up. We compared OS between SCCP patients and population‐based controls in a stage‐specific fashion. Smoothed cumulative incidence plots displayed cancer‐specific mortality (CSM) versus other‐cause mortality (OCM). Results Of 2282 SCCP patients, the stage distribution was as follows: stage I 976 (43%) versus stage II 826 (36%) versus stage III 302 (13%) versus stage IV 178 (8%). At 5 years, OS of SCCP patients versus age‐matched population‐based controls was as follows: stage I 63% versus 80% (Δ = 17%), stage II 50% versus 80% (Δ = 30%), stage III 39% versus 84% (Δ = 45%), stage IV 26% versus 87% (Δ = 61%). At 5 years, CSM versus OCM in SCCP patients according to stage was as follows: stage I 12% versus 24%, stage II 22% versus 28%, stage III 47% versus 14%, and stage IV 60% versus 14%. Conclusion SCCP patients exhibit worse OS across all stages. The difference in OS at 5 years between SCCP and age‐matched male population‐based controls ranged from 17% to 61%. At 5 years, CSM accounted for 12% to 60% of all deaths, across all stages.

Background: Compelling evidence has accumulated on the role of oxidative stress on the endothelial cell (EC) dysfunction underlying acute coronary syndrome. However, unveiling the underlying metabolic determinants has been hampered by the scarcity of appropriate cell models to address cell-autonomous mechanisms of ED dysfunction. Methods: We have generated endothelial cells derived from thrombectomy specimens from patients affected with acute myocardial infarction (AMI) and conducted phenotypical and metabolic characterization, focused on central carbon metabolism. Results: AMI-derived endothelial cells (AMIECs), but not control healthy coronary endothelial cells, display impaired growth, migration and tubulogenesis. Metabolically, AMIECs displayed augmented reactive oxygen species (ROS) and glutathione intracellular content, along with a diminished glucose consumption coupled to high lactate production. Consistent with diminished glycolysis in AMIECs, the protein levels of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase type 3, PFKFB3, were downregulated. In contrast, PFKFB4 levels were upregulated, suggesting a shunting of glycolysis towards the pentose phosphate pathway (PPP), supported by upregulation in AMIECs of G6PD, the key enzyme in the oxidative branch of the PPP. Further, the glutaminolytic enzyme GLS was upregulated in AMIECs, providing a mechanistic explanation for the observed increase in glutathione content. Finally, AMIECs displayed a significantly higher mitochondrial membrane potential than control ECs, which, together with high ROS levels, suggest a highly coupled mitochondrial activity in patient ECs. Conclusions: We suggest high mitochondrial proton coupling underlies the abnormally high production of ROS, balanced by PPP- and glutaminolysis-driven synthesis of glutathione, as a primary, cell-autonomous abnormality driving EC dysfunction in AMI. Funding: European Commission Horizon 2020; CIBER- Carlos III National Institute of Health, Spain; Ministerio de Economia y Competitividad (MINECO) and Ministerio de Ciencia e Innovación, Spain; Generalitat de Catalunya-AGAUR, Catalonia; Plataforma Temática Interdisciplinar Salud Global (PTI-SG), Spain; British Heart Foundation, UK.

From an analysis of the most recent case law of the CJEU, it becomes clear that it has taken a troublesome position on the interpretation of the Directive on Unfair Contract Terms (UCTD) and this could result in significant repercussions in terms of effective protection afforded to consumers and difficulties imposed on traders. More specifically, the CJEU’s main interpretive difficulties have focused on Article 6 of the UCTD and namely on the question of whether the non-binding nature of unfair terms implies the preclusion of contract revision and whether the UCTD legitimises rules that primarily serve to sanction sellers and suppliers rather than to ensure a rebalancing based on the principle of contract equality.

Background Systemic infection has always been considered a relative contraindication to neuraxial anesthesia, despite the fact that infectious complications are relatively uncommon. Pregnancy-related physiological changes and coronavirus disease (COVID-19) neurotropic features may facilitate the virus’ entry into the central nervous system. The principal aim of this study was to test the safety of spinal anesthesia in “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2)-positive pregnant women and to examine cerebrospinal fluid (CSF) characteristics. Methods We conducted a prospective observational single-center study in asymptomatic or paucisymptomatic consecutive pregnant SARS-CoV-2 patients who underwent spinal anesthesia for cesarean section. Women with severe infection were excluded because they underwent general anesthesia. At the time of spinal anesthesia, we collected CSF samples, and then we performed a chemical-physical analysis to look for signs of inflammation and for SARS-CoV-2 genome. Results We included 26 women. No spinal anesthesia complications were reported in the perioperative period and after 2 months. All CSF samples were crystal clear, and all physical-chemical values were within physiological ranges: the median concentration of CSF/plasma glucose ratio was 0.66, IQR 0.5500 (0.6000–0.7100), and the average CSF protein concentration value was 23.2 mg/dl (SD 4.87). In all samples, genomes of SARS-CoV-2 and other neurotropic viruses were not detected. Conclusions Spinal anesthesia was safe in SARS-CoV-2 pregnant women with mild disease; no clinical maternal complications were detected, and no CSF changes indicative of inflammatory or infectious diseases that would compromise the safety of the procedure were found.