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Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4 Hz) and alpha (8-12 Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder. The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals. Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75-0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals. In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal "hub" oscillating at the alpha frequency in quiet wakefulness as a brain network disorder., (Copyright © 2022. Published by Elsevier Inc.)

Summary: Occupational stress can exceed the workers' individual capacity to adapt, and cause psychopathological conditions, including adjustment disorder (AD) and post-traumatic stress disorder (PTSD), for which medico-legal reporting is mandatory by law. Since the early 2000s, an interdisciplinary diagnostic protocol has been in use at our Institute to address patients towards an appropriate therapeutic path, in order to promote their psychological well-being and work reintegration. In 2017, the protocol was updated and expanded. The current version (MaSD-2) includes: occupational medicine examination, psychological counselling, psychiatric interview, and psychodiagnostic testing: Short-Negative Acts Questionnaire (S-NAQ), Cognitive Behavioral Assessment 2.0 (CBA-2.0), SCID (Structured Clinical Interview for DSM: Diagnostic and Statistical Manual of Mental Disorders), Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF), Maugeri Stress Index - Reduced form (MASI-R). Between 2017 and 2019, we used the MaSD-2 to assess, for suspected psychopathological work-related problems, 198 patients (120 women and 78 men; mean age   SD: 47.9   9.0 years). Nine (4.5%), already examined with the original version of the protocol, received diagnostic confirmation (2 cases of paranoid personality disorder, 7 of work-related anxiety-depressive disorder). Of the other 189 subjects, three (1.6%) were not affected by psychiatric disease, 12 (6.3%) had a psychiatric disorder (e.g., anxiety disorder, mood disorder, personality disorder) independent of work, 160 (84.7%) a work-related anxiety and/or depressive disorder. DA was identified in 12 cases (6.3%), and two patients (1.1%) were diagnosed with DA in pre-existent DPTS, for a total of 14 medico-legal reports of occupational disease. Compared to the past, the case record presents a much higher percentage of psychiatric disorders related to occupational stress. This may be due to a greater sensitivity of the new diagnostic protocol, and to a better selection of the patients referred to us. Women and tertiary workers continue to be at greater risk, with significant involvement of health professionals. Diagnoses of DA and DPTS remain rare, confirming the need for a rigorous and cautious interdisciplinary approach, aimed at selecting the cases for which to start medico-legal procedures. Finally, the study calls for adequate preventive measures., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by GIMLE.)

With the advancement of technology, electric equipment and loads have become more sensitive to problems related to power quality, such as voltage sag, swell, imbalances, and harmonics. To detect faults and to protect sensitive loads from these voltage distortions, a Dynamic Voltage Restorer (DVR) series compensator is among the best available cost-effective solutions. One of the main goals of the DVR is to achieve a control structure that is robust, stable, and can handle properly the disturbances (e.g., grid voltage issues, load current, and fluctuations at the DC link voltage) and model uncertainties (e.g., inverters and filter parameters). In this work, a novel framework control strategy based on Uncertainty and Disturbance Estimator (UDE) is proposed to improve the response of the DVR to properly compensate the load voltage under a variety of power quality issues, particularly the ones associated with the grid voltage disturbances. Additionally, the stability of the proposed control system is analyzed and validated using the Lyapunov stability theory. The advantages of the new control system are robustness, simplified design, good harmonic rejection, low tracking error, fast response, and sinusoidal reference tracking without the need for voltage transformations or specific frequency tuning (e.g., abc-dq0 and Proportional-Resonant). This research uses the MATLAB/Simulink software to validate the effectiveness of the proposed scheme under a diverse set of conditions with no control limitations. Moreover, the designed controller is tested under real conditions using Hardware-In-the-Loop (HIL) validation with OPAL-RT real-time simulator coupled with a TI Launchpad microcontroller. The results demonstrate a good performance of the proposed control strategy for a quick transient response and a great harmonic rejection when subject to grid voltage distortions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

The transition from integrated petrochemical complexes toward decentralized chemical plants utilizing distributed feedstocks calls for simpler downstream unit operations. Less separation steps are attractive for future scenarios and provide an opportunity to design the next-generation catalysts, which function efficiently with effluent reactant mixtures. The methanol to olefins (MTO) reaction constitutes the second step in the conversion of CO 2 , CO, and H 2 to light olefins. We present a series of isomorphically substituted zeotype catalysts with the AEI topology (MAPO-18s, M = Si, Mg, Co, or Zn) and demonstrate the superior performance of the M(II)-substituted MAPO-18s in the conversion of MTO when tested at 350 °C and 20 bar with reactive feed mixtures consisting of CH 3 OH/CO/CO 2 /H 2 . Co-feeding high pressure H 2 with methanol improved the catalyst activity over time, but simultaneously led to the hydrogenation of olefins (olefin/paraffin ratio < 0.5). Co-feeding H 2 /CO/CO 2 /N 2 mixtures with methanol revealed an important, hitherto undisclosed effect of CO in hindering the hydrogenation of olefins over the Brønsted acid sites (BAS). This effect was confirmed by dedicated ethene hydrogenation studies in the absence and presence of CO co-feed. Assisted by spectroscopic investigations, we ascribe the favorable performance of M(II)APO-18 under co-feed conditions to the importance of the M(II) heteroatom in altering the polarity of the M-O bond, leading to stronger BAS. Comparing SAPO-18 and MgAPO-18 with BAS concentrations ranging between 0.2 and 0.4 mmol/g cat , the strength of the acidic site and not the density was found to be the main activity descriptor. MgAPO-18 yielded the highest activity and stability upon syngas co-feeding with methanol, demonstrating its potential to be a next-generation MTO catalyst., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Among healthcare professionals working with COVID-19 patients, general practitioners (GPs) are under considerable pressure and may develop adverse mental health outcomes., Objectives: To assess mental health outcomes on GPs working during the COVID-19 pandemic and to explore their associations with personal characteristics and features of GP practices., Methods: Observational cross-sectional study conducted on a sample of GPs working in Verona province (Italy) during the first pandemic wave. Participants were invited to complete a web-based form addressing socio-demographic and work-related information, previous practice organization, practice re-organization during the COVID-19 pandemic, and a set of measures for post-traumatic stress (IES-R), anxiety (SAS), depression (PHQ-9), and burnout (MBI-GS)., Results: A total of 215 GPs (38.3% of the eligible population) participated. Overall, 44.7% reported COVID-19-related traumatic events; among these, 35.9% (95% CI, 26%‒46%) developed symptoms of post-traumatic distress. Furthermore, 36% (95% CI, 29%‒43%) reported symptoms of anxiety, 17.9% (95% CI, 12%‒23%) symptoms of at least moderate depression, and 25.4% (95% CI, 19%‒32%) symptoms of burnout. Multivariate regressions showed that being quarantined or admitted for COVID-19 was associated with all the mental health outcomes considered. Being female, working in rural settings, and having less professional experience were associated with higher anxiety and depression. The ability to diagnose COVID-19 increased self-perceived professional efficacy, thus contributing to burnout reduction., Conclusion: The high prevalence of adverse mental health outcomes among GPs during the pandemic highlights the importance of timely interventions in this population and promoting targeted preventive actions in the event of future healthcare crises., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

A series of Cu(I) complexes of bidentate or tetradentate Schiff base ligands bearing either 1- H -imidazole or pyridine moieties were synthesized. The complexes were studied by a combination of NMR and X-ray spectroscopic techniques. The differences between the imidazole- and pyridine-based ligands were examined by 1 H, 13 C and 15 N NMR spectroscopy. The magnitude of the 15 N imine coordination shifts was found to be strongly affected by the nature of the heterocycle in the complexes. These trends showed good correlation with the obtained Cu-N imine bond lengths from single-crystal X-ray diffraction measurements. Variable-temperature NMR experiments, in combination with diffusion ordered spectroscopy (DOSY) revealed that one of the complexes underwent a temperature-dependent interconversion between a monomer, a dimer and a higher aggregate. The complexes bearing tetradentate imidazole ligands were further studied using Cu K-edge XAS and VtC XES, where DFT-assisted assignment of spectral features suggested that these complexes may form polynuclear oligomers in solid state. Additionally, the Cu(II) analogue of one of the complexes was incorporated into a metal-organic framework (MOF) as a way to obtain discrete, mononuclear complexes in the solid state., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. European Journal of Inorganic Chemistry published by Wiley-VCH GmbH.)

Introduction: Despite the development of several recommendations, glycemic control in a large proportion of patients with type 2 diabetes, including those treated with insulin, remains suboptimal. This study is aimed to identify a set of actions to promote the reduction of inappropriate clinical practices in type 2 diabetes failing basal insulin supported oral therapy (BOT)., Methods: A panel of diabetes specialists was assembled to identify a list of ten corrective actions, "things not to do," for the management of type 2 diabetes: five concerning treatments, procedures and diagnostic tests and five about relationship, communication and information. The Choosing Wisely methodology and approach were the inspiration., Results: A total of 73/73 (100%) panelists responded to the survey. Twenty-four actions were proposed. The final list of inappropriate actions deemed most important to improve the management of patients with type 2 diabetes failing BOT were: (1) do not use secretagogues-do not neglect the use of innovative glucose-lowering agents; (2) do not underestimate the risk of lack of hypoglycemia awareness; (3) do not underestimate the benefit of personalization of therapy; (4) do not delay insulin intensification; (5) do not delay modification of the therapeutic regimen. In the area of patient communication, the following actions were identified: (1) do not fail to train in the management of hypoglycemia; (2) do not underestimate whether the patient has understood the modification of therapy; (3) do not prescribe injection therapy without adequately instructing the patient to titrate it; (4) do not ignore the patient's adherence; (5) do not stop listening to the patient and verify learning., Conclusion: A set of corrective experience-based actions to enact in a timely manner, which can assist physicians in improving clinical outcomes and patients' needs in terms of communications and interaction, is proposed. The list is intended to promote discussions among diabetes specialists to provide high-value diabetes care., (© 2021. The Author(s).)

The speciation of framework-interacting Cu II sites in Cu-chabazite zeolite catalysts active in the selective catalytic reduction of NO x with NH 3 is studied, to investigate the influence of the Al content on the copper structure and their reactivity towards a NO/O 2 mixture. To this aim, three samples with similar Cu densities and different Si/Al ratios (5, 15 and 29) were studied using in situ X-ray absorption spectroscopy (XAS), FTIR and diffuse reflectance UV-Vis during pretreatment in O 2 followed by the reaction. XAS and UV-Vis data clearly show the main presence of Z 2 Cu II sites (with Z representing a framework negative charge) at a low Si/Al ratio, as predicted. EXAFS wavelet transform analysis showed a non-negligible fraction of proximal Z 2 Cu II monomers, possibly stabilized into two 6-membered rings within the same cage. These sites are not able to form Cu-nitrates by interaction with NO/O 2 . By contrast, framework-anchored Z[Cu II (NO 3 )] complexes with a chelating bidentate structure are formed in samples with a higher Si/Al ratio, by reaction of NO/O 2 with Z[Cu II (OH)] sites or structurally similar mono- or multi-copper Z x [Cu II x O y ] sites. Linear combination fit (LCF) analysis of the XAS data showed good agreement between the fraction of Z[Cu II (OH)]/Z x [Cu II x O y ] sites formed during activation in O 2 and that of Z[Cu II (NO 3 )] complexes formed by reaction with NO/O 2 , further confirming the chemical inertia of Z 2 Cu II towards these reactants in the absence of solvating NH 3 molecules.

Aims: Nephropathy is a complication of type 2 diabetes, with increased albuminuria and reduced glomerular filtration rate (GFR) as biomarkers. Rates of progression to end-stage-renal disease are variable among patients. In this study we have examined the GFR decline in newly diagnosed T2DM., Methods: A cohort of 410 patients with newly diagnosed T2DM and with at least four serum creatinine during the follow-up period were recruited. A linear model was used to calculate the decline in eGFR. A multivariable logistic model was used to identify independent predictors of rapid eGFR decline., Results: Average follow-up was 12.4 years. The eGFR change was -0.80 ± 2.23 ml/min/1.73 m 2 per year. Patients were arbitrarily stratified into rapid decliners (≤-3.0 ml/min/1.73 m 2 per year), moderate decliners (-2.9/-1 ml/min/1.73 m 2 per year) and slow/no decliners (>-1.0 ml/min/1.73 m 2 per year). Subjects in the 3 categories were 11.4%, 27.3%, and 61.3%, respectively. Albuminuria was the stronger predictor of rapid eGFR decline., Conclusions: A rapid decline in eGFR occurs in approximately 1 out of 10 newly diagnosed subjects. This rapid decline can be predicted by widely accessible clinical features, such as albuminuria. Identification of rapid decliners may help to reduce progression toward advanced stages of nephropathy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Post-traumatic stress disorder (PTSD) may arise after events involving a risk to physical integrity or to life, one's own or that of others. It is characterized by intrusive symptoms, avoidance behaviors, and hyper-excitability. Outside certain categories (e.g., military and police), the syndrome is rarely described in the occupational setting. We report here five unusual cases of work-related PTSD, diagnosed with an interdisciplinary protocol (occupational health visit, psychiatric interview, psychological counselling and testing): (1) a 51-yr-old woman who had undergone three armed robbery attempts while working in a peripheral post office; (2) a 53-yr-old maintenance workman who had suffered serious burns on the job; (3) a 33-yr-old beauty center receptionist after sexual harassment and stalking by her male employer; (4) a 57-yr-old male psychiatrist assaulted by a psychotic outpatient; (5) a 40-yr-old woman, sales manager in a shoe store, after physical aggression by a thief. All patients required psychiatric help and pharmacological treatment, with difficulty of varying degrees in resuming work. We conclude that PTSD can develop even in professional categories generally considered to be at low risk. In such cases, a correct interdisciplinary diagnostic approach is fundamental for addressing therapy and for medico-legal actions.

Water is a molecule always present in the reaction environment in photocatalytic and biomedical applications of TiO 2 and a better understanding of its interaction with the surface of TiO 2 nanoparticles is crucial to develop materials with improved performance. In this contribution, we first studied the nature and the surface structure of the exposed facets of three commercial TiO 2 samples (i.e., TiO 2 P25, SX001, and PC105) by electron microscopy and IR spectroscopy of adsorbed CO. The morphological information was then correlated with the water adsorption properties, investigated at the molecular level, moving from multilayers of adsorbed H 2 O to the monolayer, combining medium- and near-IR spectroscopies. Finally, we assessed in a quantitative way the surface hydration state at different water equilibrium pressures by microgravimetric measurements.

In the last decade, microRNAs have been increasingly recognized as key modulators of glial development. Recently, we identified miR-125a-3p as a new player in oligodendrocyte physiology, regulating in vitro differentiation of oligodendrocyte precursor cells (OPCs). Here, we show that miR-125a-3p is upregulated in active lesions of multiple sclerosis (MS) patients and in OPCs isolated from the spinal cord of chronic experimental autoimmune encephalomyelitis (EAE) mice, but not in those isolated from the spontaneously remyelinating corpus callosum of lysolecithin-treated mice. To test whether a sustained expression of miR-125a-3p in OPCs contribute to defective remyelination, we modulated miR-125a-3p expression in vivo and ex vivo after lysolecithin-induced demyelination. We found that lentiviral over-expression of miR-125a-3p impaired OPC maturation, whereas its downregulation accelerated remyelination. Transcriptome analysis and luciferase reporter assay revealed that these effects are partly mediated by the direct interaction of miR-125a-3p with Slc8a3, a sodium-calcium membrane transporter, and identified novel candidate targets, such as Gas7, that we demonstrated necessary to correctly address oligodendrocytes to terminal maturation. These findings show that miR-125a-3p upregulation negatively affects OPC maturation in vivo, suggest its role in the pathogenesis of demyelinating diseases and unveil new targets for future promyelinating protective interventions., (© 2020 Wiley Periodicals, Inc.)

The NH 3 -mediated selective catalytic reduction (NH 3 -SCR) of NOx over Cu-ion-exchanged chabazite (Cu-CHA) catalysts is the basis of the technology for abatement of NOx from diesel vehicles. A crucial step in this reaction is the activation of oxygen. Under conditions for low-temperature NH 3 -SCR, oxygen only reacts with Cu I ions, which are present as mobile Cu I diamine complexes [Cu I (NH 3 ) 2 ] + . To determine the structure and reactivity of the species formed by oxidation of these Cu I diamine complexes with oxygen at 200 °C, we have followed this reaction, using a Cu-CHA catalyst with a Si/Al ratio of 15 and 2.6 wt% Cu, by X-ray absorption spectroscopies (XANES and EXAFS) and diffuse reflectance UV-Vis spectroscopy, with the support of DFT calculations and advanced EXAFS wavelet transform analysis. The results provide unprecedented direct evidence for the formation of a [Cu 2 (NH 3 ) 4 O 2 ] 2+ mobile complex with a side-on μ-η 2 ,η 2 -peroxo diamino dicopper(II) structure, accounting for 80-90% of the total Cu content. These [Cu 2 (NH 3 ) 4 O 2 ] 2+ are completely reduced to [Cu I (NH 3 ) 2 ] + at 200 °C in a mixture of NO and NH 3 . Some N 2 is formed as well, which suggests the role of the dimeric complexes in the low-temperature NH 3 -SCR reaction. The reaction of [Cu 2 (NH 3 ) 4 O 2 ] 2+ complexes with NH 3 leads to a partial reduction of the Cu without any formation of N 2 . The reaction with NO results in an almost complete reduction to Cu I , under the formation of N 2 . This indicates that the low-temperature NH 3 -SCR reaction proceeds via a reaction of these complexes with NO.

Cu-exchanged zeolites have been shown to possess Cu-oxo species active towards the direct methane to methanol (DMTM) conversion, carried out through a chemical-looping approach. Different Cu-zeolites have been investigated for the DMTM process, with Cu-mordenite (Cu-MOR) being among the most active. In this context, an accurate determination of the local structure and nuclearity of selective Cu-oxo species responsible for an efficient DMTM conversion still represents an ongoing challenge for characterization methods, including synchrotron-based X-ray absorption spectroscopy (XAS). Herein, we explore the potential of an alternative analysis of Extended X-ray Absorption Fine Structure (EXAFS) data using wavelet transform (WT) to enhance the technique sensitivity to multimeric Cu species hosted in the MOR framework. Combining ex situ XAS measurements under model red-ox conditions with in situ data collected after the key steps of the DMTM process, we demonstrate how EXAFS-WT enables unambiguous detection of Cu-Cu scattering contributions from multimeric Cu-species. As also confirmed by complementary in situ IR spectroscopy results, these are observed to dynamically respond to the chemical environment over the different conditions probed. We finally report a proof-of-concept EXAFS fit using the WT representation, applied to the structural refinement of O 2 -activated Cu-MOR. The fitting results reveal a Cu local coordination environment consistent with mono-(μ-oxo) di-copper cores, with Cu-Cu separation of ∼3.1 Å, paving the way to future applications and developments of the method in the field of Cu-zeolite research and beyond.

Introduction: We explored the presence of chronic complications in subjects with newly diagnosed type 2 diabetes referred to the Verona Diabetes Clinic. Metabolic (insulin secretion and sensitivity) and clinical features associated with complications were also investigated., Research Design and Methods: The comprehensive assessment of microvascular and macrovascular complications included detailed medical history, resting ECG, ultrasonography of carotid and lower limb arteries, quantitative neurological evaluation, cardiovascular autonomic tests, ophthalmoscopy, kidney function tests. Insulin sensitivity and beta-cell function were assessed by state-of-the-art techniques (insulin clamp and mathematical modeling of glucose/C-peptide curves during oral glucose tolerance test)., Results: We examined 806 patients (median age years, two-thirds males), of whom prior clinical cardiovascular disease (CVD) was revealed in 11.2% and preclinical CVD in 7.7%. Somatic neuropathy was found in 21.2% and cardiovascular autonomic neuropathy in 18.6%. Retinopathy was observed in 4.9% (background 4.2%, proliferative 0.7%). Chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m 2 ) was found in 8.8% and excessive albuminuria in 13.2% (microalbuminuria 11.9%, macroalbuminuria 1.3%).Isolated microvascular disease occurred in 30.8%, isolated macrovascular disease in 9.3%, a combination of both in 9.1%, any complication in 49.2% and no complications in 50.8%.Gender, age, body mass index, smoking, hemoglobin A1c and/or hypertension were independently associated with one or more complications. Insulin resistance and beta-cell dysfunction were associated with macrovascular but not microvascular disease., Conclusions: Despite a generally earlier diagnosis for an increased awareness of the disease, as many as ~50% of patients with newly diagnosed type 2 diabetes had clinical or preclinical manifestations of microvascular and/or macrovascular disease. Insulin resistance might play an independent role in macrovascular disease., Trial Registration Number: NCT01526720., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19., Methods: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days., Results: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%)., Conclusion: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug., Competing Interests: Declaration of Competing Interests None., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aims: Psychological distress and family functioning have a considerable impact on diabetes self-management and glycaemic control in individuals with type 1 diabetes (T1D). However, the influence of both individual and family factors on glycaemic control has not been adequately investigated yet. This study aimed at examining the relationship between perceived family functioning and depressive symptoms with the frequency of capillary self-monitoring of blood glucose (SMBG) and glycaemic control (HbA 1c ) in a large sample of adults with T1D., Methods: In a cross-sectional study design, we consecutively enrolled 90 adults with T1D diagnosis from at least 1 year and currently living in their family of origin or conjugal family from at least 1 year before the enrolment. Questionnaires were administered to assess family functioning and depressive symptoms. The SMBG frequency over the past 3 months and the most recent HbA 1c measurement were also collected in each individual. Correlation and mediation analyses were carried out., Results: Glycaemic control showed a positive relationship with depressive symptoms and family balanced cohesion, while SMBG frequency was correlated with family balanced flexibility and rigidity, but not with depressive symptoms. Mediation analyses showed that family rigidity mediates the effect of depressive symptoms on glycaemic control., Conclusions: This exploratory study highlighted the significance of a cohesive family context to facilitate the achievement of individual glycaemic goals in individuals with T1D. These observations, if confirmed in larger data sets, would timely call for a comprehensive family care assessment as part of the evaluations routinely carried out in the ambulatory care of these individuals.

Hydrolysis is normally the rate limiting step for anaerobic digestion (AD). In this study, hyper-thermophilic (70 °C) pre-treatment of chicken manure under HRTs of 10, 5, 3, 2 and 1 d(s) was investigated to enhance the hydrolysis efficiency for biogas production. In-situ phase gas stripping was integrated into the pre-treatment reactor to remove ammonia-N and to enhance the hydrolysis performance. The results showed that in-situ gas stripping removed 18%-31% of ammonia-N and improved hydrolysis by 2.6%-31.1%. The methane yield of pre-hydrolyzed chicken manure reached 518 mL g-VS -1 under optimal HRT 3 days, which was 54.6% higher than that obtained from the control reactor. However, shortening HRTs below 3 days resulted in a significant reduction in hydrolysis efficiency. The percent of hydrolysis and acidogenesis bacteria reduced to 40.6% at HRT 1 d. 16sRNA results indicated existence of methanogens in pre-hydrolysis reactor. Further optimizing of ammonia stripping was thus needed for hydrolysis pre-treatment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Context: Structured exercise programs are of great benefit for the treatment of type 2 diabetes (T2DM). However, whether aerobic (AER) or resistance (RES) exercise training exerts specific epigenetic changes through the expression profile of circulating miRNAs (c-miRNAs) is still largely unknown., Objective: To assess whether the c-miRNAs profile changes after either AER or RES training in subjects with T2DM., Design: Twenty-four patients with T2DM randomized to AER or RES training protocols were randomly selected from the Resistance vs. Aerobic Exercise in Type 2 Diabetes (RAED2) Trial (NAER = 12; NRES = 12). The baseline and post-training levels of 179 c-miRNAs were initially measured by RT-PCR in 6 individuals (NAER = 3; NRES = 3). C-miRNAs exhibiting ≥40% fold change variation and/or nominal significance from baseline were measured in the whole group., Results: Nineteen c-miRNAs were eventually assessed in the whole group. Compared with baseline, the post-training levels of miR-423-3p, miR-451a, and miR-766-3p were significantly up-regulated, irrespective of exercise type (P < 0.0026; 0.05/19), and targeted upstream pathways relevant to fatty acids biosynthesis and metabolic regulation. MiR-451a and miR-423-3p were significantly correlated with fat loss (ρ = 0.45 and 0.43, respectively) and resulted, alone or in combination, in being predictors of fat loss in generalized linear regression models including exercise type as covariate. Only the association with miR-451a eventually retained significance after further correction for age, sex, body mass index, and HbA1c., Conclusions: Exercise training in T2DM is associated with substantial c-miRNAs profile changes, irrespective of exercise type and other relevant metabolic covariates. The mechanistic significance of the observed relationship between fat loss and the epigenetic modifications induced by exercise warrants further investigation in larger datasets., (Copyright © 2019 Endocrine Society.)

Methicillin-resistant Staphylococcus aureus (MRSA) clones are rapidly increasing beyond the hospital into the community, livestock farming and environmental settings. An Italian man, a professional diver working in Egypt, was admitted to Infectious Diseases Clinic-ASST Fatebenefratelli Sacco for ulcerative skin lesions. An MRSA strain was isolated from the lesions' purulent exudate and the nasal colonization was also ascertained. The strain, characterized by whole genome sequencing, resulted to be Panton-Valentine Leukocidin (PVL) positive, SCCmecI - spa-type t504, and belonging to the sequence type 1153, sporadically described worldwide.

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans , 215  C. dubliniensis , 4,418  C. glabrata species complex, 157  C. guilliermondii ( Meyerozyma guilliermondii ), 676  C. krusei ( Pichia kudriavzevii ), 298  C. lusitaniae ( Clavispora lusitaniae ), 911  C. parapsilosis sensu stricto , 3,691  C. parapsilosis species complex, 36  C. metapsilosis , 110  C. orthopsilosis , 1,854  C. tropicalis , 244 Saccharomyces cerevisiae , 1,409 Aspergillus fumigatus , 389  A. flavus , 130  A. nidulans , 233  A. niger , and 302  A. terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 ( C. albicans ), ERG11 and MRR1 ( C. parapsilosis ), cyp51A ( A. fumigatus ), and CDR2 and CDR1 overexpression ( C. albicans and C. glabrata , respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants., (Copyright © 2018 American Society for Microbiology.)

In this work, we show the potentiality of operando FTIR spectroscopy to follow the formation of Cu II -(N,O) species on Cu exchanged chabazite zeolites (Cu-CHA), active for the selective catalytic reduction of NO x with NH 3 (NH 3 -SCR). In particular, we investigated the reaction of NO and O 2 at low temperature (200 and 50 °C) on a series of Cu-CHA zeolites with different composition (Si/Al and Cu/Al ratios), to investigate the nature of the formed copper nitrates, which have been proposed to be key intermediates in the oxidation part of the SCR cycle. Our results show that chelating bidentate nitrates are the main structures formed at 200 °C. At lower temperature a mixture of chelating and monodentate nitrates are formed, together with the nitrosonium ion NO + , whose amount was found to be proportional to the zeolite Brønsted site concentration. Nitrates were found to mainly form with Cu II ions stabilized by one negative framework charge (Z), Z-[Cu(OH] I or Z-[Cu(O 2 ] I , without involvement of Z 2 -Cu II ones. This evidence, together with the absence of bridging nitrates in samples with high probability for Cu-Cu pairs, indicate that the nitrate ligands are not able to mobilize copper ions, at variance with what recently reported for NH 3 . Finally, water was found to replace preformed chelating copper nitrates and deplete NO + (though with different kinetics) at both temperatures, while favouring the presence of monodentate ones., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: To assess the association of psychological variables on leisure-time physical activity and sedentary time in men and women with type 2 diabetes mellitus (T2D)., Methods: In this cross-sectional study, we evaluated 163 patients with T2D, consecutively recruited at the Diabetes Centre of the Verona General Hospital. Scores on depression and anxiety symptoms, psychosocial factors (including self-efficacy, perceived interference, perceived severity, social support, misguided support behaviour, spouse's positive behaviour), physical activity and time spent sitting were ascertained using questionnaires responses to the Beck Depression Inventory-II, Beck Anxiety Inventory, Multidimensional Diabetes Questionnaire, International Physical Activity Questionnaire., Results: Physical activity was significantly associated with higher social support in women and with increased self-efficacy in men. Sedentary time was significantly associated with higher perceived interference, anxiety and depressive symptoms, and with reduced diabetes self-efficacy in women, while it was associated solely with anxiety in men. Depressive symptoms and self-efficacy in women and anxiety symptoms in men were independent predictors of sedentary time when entered in a multivariable regression model also including age, BMI, haemoglobin A1c, diabetes duration, perceived interference and self-efficacy as covariates., Conclusions: Lower self-efficacy and higher symptoms of depression were closely associated with increased sedentary time in women, but not in men, with T2D. It is possible that individualized behavioural interventions designed to reduce depressive symptoms and to improve diabetes self-efficacy would ultimately reduce sedentary behaviours, particularly in women with T2D.

Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreER T2 xCAG-eGFP mice) allowing to follow the final fate of GPR17 + cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult. In both models, demyelination induced a strong increase of fluorescent GFP + cells at damaged areas. However, only in the cuprizone model reacting GFP + cells terminally differentiated to mature oligodendrocytes, thus contributing to remyelination. In EAE, GFP + cells were blocked at immature stages and never became myelinating oligodendrocytes. We suggest these strikingly distinct fates be due to different permissiveness of the local CNS environment. Based on previously reported GPR17 activation by emergency signals (e.g., Stromal Derived Factor-1), we propose that a marked inflammatory milieu, such as that reproduced in EAE, induces GPR17 overactivation resulting in impaired downregulation, untimely and prolonged permanence in OPCs, leading, in turn, to differentiation blockade. Combined treatments with remyelinating agents and anti-inflammatory drugs may represent new potential adequate strategies to halt neurodegeneration and foster recovery., (© 2018 The Authors GLIA Published by Wiley Periodicals, Inc.)

Scedosporium apiospermum is a medically important fungal pathogen that causes a wide range of infections in humans. There are relatively few antifungal agents that are active against Scedosporium spp. Little is known about the pharmacodynamics of voriconazole against Scedosporium Both static and dynamic in vitro models of invasive scedosporiosis were developed. Monoclonal antibodies that target a soluble cell wall antigen secreted by Scedosporium apiospermum were used to describe the pharmacodynamics of voriconazole. Mathematical pharmacokinetic-pharmacodynamic models were fitted to the data to estimate the drug exposure required to suppress the release of fungal antigen. The experimental results were bridged to humans using Monte Carlo simulation. All 3 strains of S. apiospermum tested invaded through the cellular bilayer of the in vitro models and liberated antigen. There was a concentration-dependent decline in the amount of antigen, with near maximal antifungal activity against all 3 strains being achieved with voriconazole at 10 mg/liter. Similarly, there was a drug exposure-dependent decline in the amount of circulating antigen in the dynamic model and complete suppression of antigen, with an area under the concentration-time curve (AUC) of approximately 80 mg · h/liter. A regression of the AUC/MIC versus the area under the antigen-time curve showed that a near maximal effect was obtained with an AUC/MIC of approximately 100. Monte Carlo simulation suggested that only isolates with an MIC of 0.5 mg/liter enabled pharmacodynamic targets to be achieved with a standard regimen of voriconazole. Isolates with higher MICs may need drug exposure targets higher than those currently recommended for other fungi., (Copyright © 2018 American Society for Microbiology.)

Macroscopic frictional sliding emerges from atomic-scale interactions and processes at the contact interface, but bridging the gap between micro and macro scales still remains an unsolved challenge. Direct imaging of the contact surface and simultaneous measurement of stress fields during macroscopic frictional slip revealed the formation of crack precursors, questioning the traditional picture of frictional contacts described in terms of a single degree of freedom. Here we study the onset of frictional slip on the atomic scale by simulating the motion of an aluminum block pushed by a slider on a copper substrate. We show the formation of dynamic slip front propagation and precursory activity that resemble macroscopic observations. The analysis of stress patterns during slip, however, reveals subtle effects due to the lattice structures that hinder a direct application of linear elastic fracture mechanics. Our results illustrate that dynamic front propagation arises already on the atomic scales and shed light on the connections between atomic-scale and macroscopic friction.

An increased aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) has been widely used as a marker of advanced hepatic fibrosis. Increased AAR was also shown to be significantly associated with the risk of developing cardiovascular (CV) disease. The aim of this study was to assess the relationship between the AAR and mortality risk in a well-characterized cohort of patients with type 2 diabetes.A cohort of 2529 type 2 diabetic outpatients was followed-up for 6 years to collect cause-specific mortality. Cox regression analyses were modeled to estimate the independent association between AAR and the risk of all-cause and CV mortality.Over the 6-year follow-up period, 12.1% of patients died, 47.5% of whom from CV causes. An increased AAR, but not its individual components, was significantly associated with an increased risk of all-cause (adjusted-hazard risk 1.83, confidence interval [CI] 95% 1.14-2.93, P = 0.012) and CV (adjusted-hazard risk 2.60, CI 95% 1.38-4.90, P < 0.003) mortality after adjustment for multiple clinical risk factors and potential confounding variables.The AAR was independently associated with an increased risk of both all-cause and CV mortality in patients with type 2 diabetes. These findings suggest that an increased AAR may reflect more systemic derangements that are not simply limited to liver damage. Further studies are needed to elucidate the pathophysiological implications of an increased AAR., Competing Interests: The authors have no conflicts of interest to disclose.

The small-pore Cu-CHA zeolite is today the object of intensive research efforts to rationalize its outstanding performance in the NH3-assisted selective catalytic reduction (SCR) of harmful nitrogen oxides and to unveil the SCR mechanism. Herein we exploit operando X-ray spectroscopies to monitor the Cu-CHA catalyst in action during NH3-SCR in the 150-400 °C range, targeting Cu oxidation state, mobility, and preferential N or O ligation as a function of reaction temperature. By combining operando XANES, EXAFS, and vtc-XES, we unambiguously identify two distinct regimes for the atomic-scale behavior of Cu active-sites. Low-temperature SCR, up to ∼200 °C, is characterized by balanced populations of Cu(I)/Cu(II) sites and dominated by mobile NH3-solvated Cu-species. From 250 °C upward, in correspondence to the steep increase in catalytic activity, the largely dominant Cu-species are framework-coordinated Cu(II) sites, likely representing the active sites for high-temperature SCR.

Exercise has a powerful action on metabolism, and adaptation of the body to changes induced by exercise is fundamental to be able to provide the energy required for muscle contraction and physiological functions of vital tissues. Depending on the intensity and duration of exercise, different mechanisms are called on to make energy available, and under homeostatic control, this is guaranteed by rapid and coordinated changes in the secretion of several hormones. Molecular mechanisms controlling muscle function and fiber phenotype are related to the specific mode of muscle activation. We can distinguish between two fundamental types of physical activity, endurance exercise and strength exercise, although there is a continuum between these exercise modalities. Besides the acute changes induced by a single exercise session, regular exercise may induce chronic adaptations, improving exercise capacity and affecting energy metabolism. Notably, although acute metabolic effects of exercise are mostly due to insulin-independent effects, exercise training may improve muscle insulin sensitivity and is considered a key tool in the prevention and treatment of metabolic disorders. This chapter focuses on the biochemistry of energy supply to the exercising muscle, on molecular mechanisms involved and on the physiology of energy metabolism during exercise in healthy subjects and patients with insulin resistance and/or diabetes., (© 2016 S. Karger AG, Basel.)

Objective: Limited literature has shown that maximal oxygen consumption (V'O2max), that is the maximal capacity of an individual to perform aerobic work, may be lowered in overweight/obese women with polycystic ovary syndrome (PCOS). However, it remains unclear whether this impairment is associated with PCOS per se or is entirely due to body fat excess. Our objective was to assess whether cardiorespiratory fitness is altered in normal-weight PCOS women and to investigate which factors are associated with this phenomenon., Subjects: Fifteen normal-weight PCOS women and 15 age- and BMI-matched healthy controls. Fourteen subjects in each group completed the protocol., Measurements: V'O2max and ventilatory thresholds (maximal incremental cycle ergometer test with breath-by-breath analysis of gas exchange), insulin sensitivity (hyperinsulinaemic euglycaemic clamp) and androgenaemia (serum total and free testosterone, measured by liquid chromatography mass spectrometry and equilibrium dialysis) were accurately assessed., Results: Maximal V'O2 and power were strikingly impaired in normal-weight PCOS individuals, as compared with healthy controls (29·4 ± 1·5 vs 35·8 ± 1·6 ml O2/kg/min, P = 0·008; 138 ± 6 vs 170 ± 10 W, P = 0·011, respectively). Similarly, oxygen consumption and power at both the first and second ventilatory thresholds were significantly lower in PCOS subjects than in healthy women. In multiple regression analysis, V'O2max was negatively predicted by serum-free testosterone levels, but not by body fat mass and glucose disposal rate (R(2) = 0·45 P = 0·013)., Conclusions: Cardiorespiratory fitness is impaired in normal-weight PCOS women. Androgen excess but not insulin sensitivity is associated with this alteration., (© 2015 John Wiley & Sons Ltd.)

Designing and controlling particle self-assembly into robust and reliable high-performance smart materials often involves crystalline ordering in curved spaces. Examples include carbon allotropes like graphene, synthetic materials such as colloidosomes, or biological systems like lipid membranes, solid domains on vesicles, or viral capsids. Despite the relevance of these structures, the irreversible deformation and failure of curved crystals is still mostly unexplored. Here, we report simulation results of the mechanical deformation of colloidal crystalline shells that illustrate the subtle role played by geometrically necessary topological defects in controlling plastic yielding and failure. We observe plastic deformation attributable to the migration and reorientation of grain boundary scars, a collective process assisted by the intermittent proliferation of disclination pairs or abrupt structural failure induced by crack nucleating at defects. Our results provide general guiding principles to optimize the structural and mechanical stability of curved colloidal crystals.

Aims: Somatic neuropathy is a chronic complication of diabetes. The purpose of our study was to determine prevalence and clinical variables associated with somatic neuropathy applying a simple screening method., Methods: All outpatients with type 2 diabetes attending our diabetic clinic were offered to participate into a diabetic foot screening program, in the period January 2004-December 2012. A total of 3,591 diabetic patients (55.5% men, age 68±10years) underwent detection of somatic neuropathy using the Michigan Neuropathy Screening Instrument in its parts of symptoms (administering a questionnaire) and clinical assessment slightly modified (evaluating foot inspection, vibration sensation by biothesiometer, ankle reflexes)., Results: The prevalence of somatic neuropathy was 2.2% in men and 5.5% in women (p<0.001) when assessed by symptom questionnaire, whereas it was 30.5% in men and 30.8% (p=NS) in women when identified by clinical assessment. In subjects with somatic neuropathy macro- and microvascular complications of diabetes were significantly more common. In multivariate logistic regression analyses BMI, HbA1c and ankle/brachial index independently predicted the presence of neuropathy., Conclusion: The prevalence of somatic neuropathy in type 2 diabetes is nearly 30% when searched with clinical examination. Poor metabolic control, excess body weight and peripheral arteriopathy are independent markers of somatic neuropathy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Cardiovascular autonomic diabetic neuropathy (CAN) is a serious complication of diabetes. No reliable data on the prevalence of CAN among patients with newly diagnosed type 2 diabetes are available. Therefore, the aim of this study was to estimate the prevalence of CAN among patients with newly diagnosed type 2 diabetes., Research Design and Methods: A cohort of 557 patients with newly diagnosed type 2 diabetes with cardiovascular autonomic test results available was selected. Early and confirmed neuropathy were assessed using a standardized methodology and their prevalences determined. A multivariate logistic regression analysis was modeled to study the factors associated with CAN., Results: In the entire cohort, the prevalence of confirmed CAN was 1.8%, whereas that of early CAN was 15.3%. Prevalence did not differ between men and women. In the multivariate analyses BMI results were independently and significantly associated with CAN after adjusting for age, sex, hemoglobin A1c, pulse pressure, triglyceride-to-HDL cholesterol ratio, kidney function parameters, and antihypertensive treatment., Conclusions: CAN could be detected very early in type 2 diabetes. This study may suggest the importance of performing standardized cardiovascular autonomic tests after diagnosis of type 2 diabetes., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Low levels of serum 25-hydroxyvitamin D [25(OH)D] are commonly found in type 2 diabetes. We examined whether there is an association between circulating 25(OH)D concentrations and the presence of microvascular complications in people with type 2 diabetes., Research Design and Methods: We studied 715 outpatients with type 2 diabetes who regularly attended our clinic. Participants were evaluated for the presence of microvascular complications (namely retinopathy and/or nephropathy) by clinical evaluation, fundus examination, urine examination and biochemical tests. Serum 25(OH)D levels were also measured for each participant., Results: Hypovitaminosis D (ie, a serum 25(OH)D level <30 ng/mL) was found in 75.4%, while deficiency (ie, a 25(OH)D level <20 ng/mL) was found in 36.6% of these patients. Serum 25(OH)D levels decreased significantly in relation to the severity of either retinopathy or nephropathy or both. In multivariate logistic regression analysis, lower 25(OH)D levels were independently associated with the presence of microvascular complications (considered as a composite end point; OR 0.758; 95% CI 0.607 to 0.947, p=0.015). Notably, this association remained significant even after excluding those with an estimated glomerular filtration rate <60 mL/min/1.73 m(2)., Conclusions: We found an inverse and independent relationship between circulating 25(OH)D levels and the prevalence of microvascular complications in patients with type 2 diabetes. However, vitamin D may be simply a marker and causality cannot be implied from our cross-sectional study. Whether vitamin D supplementation in patients with type 2 diabetes may have beneficial effects on the risk of microvascular complications remains to be investigated.

Aspergillus spp. are among the most common causes of opportunistic invasive fungal infections in tertiary care hospitals. Little is known about the prevalence and in vitro susceptibility of Aspergillus species in Latin America, because there are few medical centers able to perform accurate identification at the species level. The purpose of this study was to analyze the distribution of cryptic and rare Aspergillus species among clinical samples from 133 patients with suspected aspergillosis admitted in 12 medical centers in Brazil and to analyze the in vitro activity of different antifungal drugs. The identification of Aspergillus species was performed based on a polyphasic approach, as well as sequencing analysis of the internal transcribed spacer (ITS) region, calmodulin, and β-tubulin genes and phylogenetic analysis when necessary. The in vitro susceptibility tests with voriconazole, posaconazole, and itraconazole were performed according to the CLSI M38-A2 document (2008). We demonstrated a high prevalence of cryptic species causing human infection. Only three isolates, representing the species Aspergillus thermomutatus, A. ochraceus, and A. calidoustus, showed less in vitro susceptibility to at least one of the triazoles tested. Accurate identifications of Aspergillus at the species level and with in vitro susceptibility tests are important because some species may present unique resistance patterns against specific antifungal drugs., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Interactions among several environmental, behavioral, social, and biological variables contribute to the epidemiology of infectious diseases (IDs) and have an impact on the healthcare system and hospitalizations. We evaluated trends in ID hospitalizations at our Department for Infectious Diseases in the last two decades to aid decision-makers in defining appropriate healthcare strategies., Methods: The discharge diagnoses of all patients admitted to the ID Department of L Sacco University Hospital between 1995 and 2011 were classified by the International Classification of Diseases (ICD-9) grouped in Major Diagnostic Categories (MDC). Linear regression was used to determine the trends in hospitalizations for each MDC. Estimates of the average annual change were based on the slope of the regression line., Results: A sharp decline in HIV/AIDS cases (-22.5 +/-6.0 cases per calendar year), and an increase in admissions for respiratory, cardiovascular, renal and musculoskeletal infections were recorded. The mean age of the patients increased by 1.2 years (+/-0.049) for each calendar year of observation (linear trend, p < 0.0001), increasing from 37.02 +/-11.91 years in 1995 to 56.02 +/-19.62 years in 2011 (p < 0.0001). The mean number of comorbidities per patient increased significantly over time (Mann-Whitney U test, p = 0.0153). From 1998/1999 to 2010/2011 the hospital length of stay (LOS) increased for cardiovascular, digestive system, musculoskeletal, and skin/subcutaneous infections, and infectious and parasitic diseases (p < 0.01). The rate of hospital stay over threshold (HSOT) increased in the last 5 years by 1.12% for every 10-year age group., Conclusions: Older age, a higher number of comorbidities, a longer hospital LOS for certain conditions, and a higher rate of HSOT characterize the patients admitted to this ID department in recent years. Despite progress in treatment and management, infectious diseases continue to be a major threat to human health. The current challenge for ID departments is the treatment of complex cases, often associated with chronic diseases in elderly patients. Continuous monitoring at a local and national level will allow early identification of changes in the epidemiological patterns of IDs and provide information for healthcare system planning.

Factors contributing to the reduced cardiorespiratory fitness typical of sedentary subjects with type 2 diabetes are still largely unknown. In this study, we assessed the relationships between cardiorespiratory fitness and abdominal and skeletal muscle fat content in 39 untrained type 2 diabetes subjects, 27 males and 12 females (mean ± SD age 56.5 ± 7.3 year, BMI 29.4 ± 4.7 kg/m(2)). Peak oxygen uptake (VO2peak) and ventilatory threshold (VO2VT) were assessed by maximal cycle ergometer exercise test, insulin sensitivity by euglycemic-hyperinsulinemic clamp, and body composition by dual-energy X-ray absorptiometry. Magnetic resonance imaging was used to evaluate visceral, total subcutaneous (SAT), superficial (SSAT) and deep sub-depots of subcutaneous abdominal adipose tissue, and sagittal abdominal diameter (SAD), as well as femoral quadriceps skeletal muscle fat content. In univariate analysis, both VO2peak and VO2VT were inversely associated with BMI, total fat mass, SAT, SSAT, and sagittal abdominal diameter. VO2peak was also inversely associated with skeletal muscle fat content. A significant direct association was observed between VO2VT and insulin sensitivity. No associations between cardiorespiratory fitness parameters and metabolic profile data were found. In multivariable regression analysis, after adjusting for age and gender, VO2peak was independently predicted by higher HDL cholesterol, and lower SAD and skeletal muscle fat content (R (2) = 0.64, p < 0.001), whereas VO2VT was predicted only by sagittal abdominal diameter (R (2) = 0.48, p = 0.025). In conclusion, in untrained type 2 diabetes subjects, peak oxygen uptake is associated with sagittal abdominal diameter, skeletal muscle fat content, and HDL cholesterol levels. Future research should target these features in prospective intervention studies.

Objective: A correlation between glucose control and 25(OH)D metabolism has been suggested by previous studies. However, this correlation has not yet been evaluated considering the impact of chronic complications of type 2 diabetes, especially the presence of nephropathy. Thus, the aim of this study was to determine the correlation between A1C and 25(OH)D in a well characterized cohort of type 2 diabetic patients., Research Design and Methods: We cross-sectionally examined the association between A1C and serum 25(OH) D in 715 type 2 diabetic patients attending our clinic during the years 2011-2012. The average age was 68±12 years (range 26-94 years). The relation between A1C and serum 25(OH)D levels was modelled by multiple linear regression analyses., Results: Serum 25(OH)D levels were inversely associated with A1C levels (r = -0.116, p = .003). This relation maintains its independence in the multivariate analysis after adjusting for age, sex, A1C, BMI, treatment and duration of diabetes and nephropathy., Conclusions: In type 2 diabetic patients, high A1C levels are associated with low concentrations of serum 25(OH)D independently of duration of diabetes, diabetic treatment and nephropathy. Future studies are needed to clarify the biological relation between glucose control and vitamin D metabolism in type 2 diabetes.

Unlabelled: Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease (NAFLD), which is extremely common in people with type 2 diabetes, no intervention studies have compared the effects of aerobic (AER) or resistance (RES) training on hepatic fat content in type 2 diabetic subjects with NAFLD. In this randomized controlled trial, we compared the 4-month effects of either AER or RES training on insulin sensitivity (by hyperinsulinemic euglycemic clamp), body composition (by dual-energy X-ray absorptiometry), as well as hepatic fat content and visceral (VAT), superficial (SSAT), and deep (DSAT) subcutaneous abdominal adipose tissue (all quantified by an in-opposed-phase magnetic resonance imaging technique) in 31 sedentary adults with type 2 diabetes and NAFLD. After training, hepatic fat content was markedly reduced (P < 0.001), to a similar extent, in both the AER and the RES training groups (mean relative reduction from baseline [95% confidence interval] -32.8% [-58.20 to -7.52] versus -25.9% [-50.92 to -0.94], respectively). Additionally, hepatic steatosis (defined as hepatic fat content >5.56%) disappeared in about one-quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group). Insulin sensitivity during euglycemic clamp was increased, whereas total body fat mass, VAT, SSAT, and hemoglobin A1c were reduced comparably in both intervention groups., Conclusion: This is the first randomized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD., (Copyright © 2013 by the American Association for the Study of Liver Diseases.)

Malignant mesothelioma is an uncommon, highly invasive tumor derived from the mesothelial cells of pleura or peritoneum characterized by poor outcome. Mesothelioma was thought to metastasize locally only via direct invasion and not have distant spread. Distant metastases were discovered mostly on post-mortem examination. The authors present a case of 62-year-old man with pleural mesothelioma and brain metastasis., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.)

Objective: To compare the performance of two glomerular filtration rate (GFR)-estimating equations in predicting the risk of all-cause and cardiovascular mortality in type 2 diabetic patients., Research Design and Methods: We followed 2,823 type 2 diabetic outpatients for a period of 6 years for the occurrence of all-cause and cardiovascular mortality. GFR was estimated using the four-variable Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation., Results: At baseline, an estimated GFR (eGFR) <60 mL/min/1.73 m(2) was present in 22.0 and 20.2% of patients using the MDRD study equation and the CKD-EPI equation, respectively. A total of 309 patients died during the follow-up (152 patients from cardiovascular causes). Both creatinine-based equations were associated with an increased risk of all-cause and cardiovascular mortality. However, the CKD-EPI equation provided a more accurate risk prediction of mortality than the MDRD study equation. Receiving operating characteristic curves showed that the areas under the curve (AUCs) for all-cause mortality (AUC 0.712 [95% CI 0.682-0.741]) and cardiovascular mortality (0.771 [0.734-0.808]) using eGFR(CKD-EPI) were significantly greater (P < 0.0001 by the z statistic) than those obtained by using eGFR(MDRD) (0.679 [0.647-0.711] for all-cause mortality and 0.739 [0.698-0.783] for cardiovascular mortality)., Conclusions: Our findings suggest that the estimation of GFR using the CKD-EPI equation more appropriately stratifies patients with type 2 diabetes according to the risk of all-cause and cardiovascular mortality compared with the MDRD study equation.

Objective: To examine the association of aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) with all-cause and cardiovascular mortality in type 2 diabetic individuals., Research Design and Methods: We retrospectively analyzed the data from 902 type 2 diabetic outpatients, who had undergone a transthoracic echocardiography for clinical reasons during the years 1992-2007. AVS and MAC were diagnosed by echocardiography, and a heart valve calcium (HVC) score was calculated by summing up the AVS and MAC variables. The study outcomes were all-cause and cardiovascular mortality., Results: At baseline, 477 (52.9%) patients had no heart valves affected (HVC-0), 304 (33.7%) had one valve affected (HVC-1), and 121 (13.4%) had both valves affected (HVC-2). During a mean follow-up of 9 years, 137 (15.2%) patients died, 78 of them from cardiovascular causes. Compared with patients with HVC-0, those with HVC-2 had the highest risk of all-cause and cardiovascular mortality, whereas those with HVC-1 had an intermediate risk (P < 0.0001 by the log-rank test). After adjustment for sex, age, BMI, systolic blood pressure, diabetes duration, A1C, LDL cholesterol, estimated glomerular filtration rate, smoking, history of myocardial infarction, and use of antihypertensive and lipid-lowering drugs, the hazard ratio of all-cause mortality was 2.3 (95% CI 1.1-4.9; P < 0.01) for patients with HVC-1 and 9.3 (3.9-17.4; P < 0.001) for those with HVC-2. Similar results were found for cardiovascular mortality., Conclusions: Our findings indicate that AVS and MAC, singly or in combination, are independently associated with all-cause and cardiovascular mortality in type 2 diabetic patients.

Context: In vitro data show that insulin may enhance basal and LH-stimulated ovarian androgen secretion, particularly in theca cells from women with polycystic ovary syndrome (PCOS). However, in vivo studies gave inconsistent results., Objective: The objective of the study was to assess whether hyperinsulinemia affects in vivo ovarian steroid secretion and steroid metabolism., Design and Settings: This was a controlled cross-sectional study, conducted in a tertiary care academic center., Participants: Nine young PCOS women participated in the study., Intervention: Participants were submitted, in two separate days, to a GnRH agonist stimulation (buserelin 100 μg, s.c.), during a 17-h hyperinsulinemic (80 mU/m(2) · min) euglycemic clamp and, as a control, during saline infusion. Adrenal steroid secretion was suppressed by dexamethasone., Main Measures: During both protocols, before and after GnRH agonist stimulation, serum insulin, gonadotropins, cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, and urinary androgen metabolites were measured., Results: Insulin increased from 25.1 ± 13.3 to 341.5 ± 102.6 mU/liter during the clamp, whereas it did not significantly change during saline infusion. Baseline steroids and gonadotropins were similar in the two protocols. During hyperinsulinemia, GnRH agonist-stimulated serum progesterone and androstenedione were significantly higher than during saline infusion, and 17-hydroxyprogesterone was of borderline significance. Moreover, 24 h after GnRH agonist stimulation, testosterone was higher after hyperinsulinemia. Serum gonadotropins and estradiol response did not differ between the protocols. Urinary androgen metabolites excretion significantly increased after GnRH agonist stimulation, but the increase was similar during insulin and saline infusions., Conclusions: These in vivo data show that sustained hyperinsulinemia potentiates gonadotropin-stimulated ovarian androgen steroidogenesis. Insulin-induced increase in ovarian hormone secretion is not accompanied by an increased steroid metabolism.

Objective: To assess differences between the effects of aerobic and resistance training on HbA(1c) (primary outcome) and several metabolic risk factors in subjects with type 2 diabetes, and to identify predictors of exercise-induced metabolic improvement., Research Design and Methods: Type 2 diabetic patients (n = 40) were randomly assigned to aerobic training or resistance training. Before and after 4 months of intervention, metabolic phenotypes (including HbA(1c), glucose clamp-measured insulin sensitivity, and oral glucose tolerance test-assessed β-cell function), body composition by dual-energy X-ray absorptiometry, visceral (VAT) and subcutaneous (SAT) adipose tissue by magnetic resonance imaging, cardiorespiratory fitness, and muscular strength were measured., Results: After training, increase in peak oxygen consumption (V(O(2peak))) was greater in the aerobic group (time-by-group interaction P = 0.045), whereas increase in strength was greater in the resistance group (time-by-group interaction P < 0.0001). HbA(1c) was similarly reduced in both groups (-0.40% [95% CI -0.61 to -0.18] vs. -0.35% [-0.59 to -0.10], respectively). Total and truncal fat, VAT, and SAT were also similarly reduced in both groups, whereas insulin sensitivity and lean limb mass were similarly increased. β-Cell function showed no significant changes. In multivariate analyses, improvement in HbA(1c) after training was independently predicted by baseline HbA(1c) and by changes in V(O(2peak)) and truncal fat., Conclusions: Resistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients. Changes after training in V(O(2peak)) and truncal fat may be primary determinants of exercise-induced metabolic improvement.

Background and Objectives: This study examined predictors of the annual decline in estimated GFR (eGFR) in patients with type 2 diabetes and preserved kidney function., Design, Setting, Participants, & Measurements: In a prospective, observational cohort study, 1682 individuals with type 2 diabetes and baseline eGFR ≥60 ml/min per 1.73 m(2) (as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation) were followed for 10 years. Linear regression was used to estimate participants' changes in eGFR over time., Results: During follow-up, 263 (15.6%) individuals had a rapid eGFR decline defined as >4.0% per year. Average eGFR decline was -5.8 ± 3 and -0.6 ± 2 ml/min per 1.73 m(2) per year in rapid decliners and nondecliners, respectively. Compared with normotensive, normoalbuminuric patients (-0.2 ± 0.2 ml/min per 1.73 m(2) per year), those with hypertension (-1.0 ± 0.1 ml/min per 1.73 m(2) per year), hemoglobin A(1c)≥7% (-1.0 ± 0.1 ml/min per 1.73 m(2) per year), longer diabetes duration (-1.0 ± 0.1 ml/min per 1.73 m(2) per year), obesity (-1.2 ± 0.1 ml/min per 1.73 m(2) per year), insulin treatment (-1.5 ± 0.1 ml/min per 1.73 m(2) per year), microalbuminuria (-1.3 ± 0.2 ml/min per 1.73 m(2) per year), or macroalbuminuria (-2.7 ± 0.4 ml/min per 1.73 m(2) per year) had significantly faster age-adjusted annual eGFR declines. Multivariable linear regression analyses revealed that albuminuria (P<0.001) was the strongest predictor of annual eGFR decline. Other independent predictors of annual eGFR decline were older age, hypertension, insulin treatment, and lower baseline eGFR., Conclusions: Annual eGFR decline is predicted by multiple modifiable risk factors in patients with type 2 diabetes and preserved kidney function.