Obstructive Sleep Apnea (OSA), an emerging health problem

Obstructive Sleep Apnea (OSA) is the most common respiratory disorder in Western societies: according to a first recent worldwide epidemiological study, it was estimated that 936 million patients aged 30-69 years with mild to moderate OSA and 425 million patients aged 30-69 years with severe OSA requiring CPAP treatment. Recently, the Centre for Research on Health and Social Care Management (CERGAS) at the Bocconi University of Milan has estimated that in Italy, the prevalence of moderate to severe OSA occurs in the 27% of the general population, with an overall prevalence of mild to medium-severe OSA of more than 24 million people aged between 15 and 74 years (54% of the adult population), while from a practical point of view, Italian doctors diagnosed only 460.000 moderate-severe patients (4 per cent of the estimated prevalence) and 230,000 patients were treated (2 per cent of the estimated prevalence), highlighting a substantial gap between diagnosis and treatment. In addition, OSA patients are often obese and the close correlation between the two conditions suggests that the prevalence of OSA will increase in the short term as obesity increases. At the individual level, OSA leads to a significant decrease in quality of life (HRQoL) and intellectual and mechanical/functional capacities with reduced physical activity, as well as a marked increase in sudden death and risk of cardiovascular and metabolic diseases. Emerging epidemiological data also suggest that the severity of OSA associated with the severity of chronic nocturnal hypoxemia (CIH) correlates with an increased risk of diabetes mellitus, metabolic syndrome (MS) and cancer. OSA is also an important risk factor for high blood pressure, acute and chronic atrial fibrillation (FAC), chronic coronary artery disease (CAD) and stroke. It is therefore intuitive that at the social level, OSA also leads to a decline in economic productivity. This article addresses OSA from a new epidemiological perspective, according to the latest prevalence studies, and addresses emerging problems related to the diagnosis

Membrane Dynamics of Spermatozoa during Capacitation: New Insight in Germ Cells Signalling

The study of germline stem cells and of germline cells has deep implications for the understanding of fertility, development and cancer. Nowadays, we are experiencing the very fascinating challenge of application of –OMICS technologies to this issue, which is opening new and unexpected horizons in virtually all the branches of biology. Here, we carried out a review of signalling systems involved in maturation of male germ cells and in the process that leads them to become fully fertile. In particular, we discuss the control mechanisms involved in capacitation and acrosome reaction that act at membrane level. Indeed, spermatozoa membranes play key roles in determining the achievement of fertility: they are the interface with the surrounding environment, they locate the signal transduction systems and they are active in recognizing and binding the oocyte. In addition, we discuss the effect of several compounds that could exert a negative effect on reproductive activity, by interfering with the endocrine axis, the so-called endocrine disruptors

Effect of Estradiol and Progesterone on ovine Amniotic Epithelial Cells

This study was designed to clarify Estradiol (E2) and Progesterone (P4) steroid effects on ovine Amniotic Epithelial Cells (oAECs) that has a conserved plasticity and highly self-renewable capacity (Parolini et al., Stem Cells, 26(2), 300–311, 2008; Barboni et al., Stem Cell Rev Rep, 10:725–741, 2014). Based on their conserved immunomodulatory properties, oAECs are suitable for allo and xeno-transplantation (Barboni et al., Cell Transplant, 21(11), 2377–2395, 2012; Muttini et al., Res Vet Sci, 94(1),158–169, 2013). To date, no information is present on the effects of prolonged steroid exposition on AECs. oAECs were cultured as previously reported (Barboni et al., Cell Transplant. 21(11), 2377–2395, 2012) and treated with 12.5μM and 25μM of E2 or P4 (Sigma-Aldrich, Milan, Italy), alone and in both combinations, for three passages. Untreated cells were marked control (CTR). At 70% confluency, cells were detached for doubling time (DT) evaluation. Cells at fourth passage were differentiated for 21 days in osteogenic media (DM) (Mattioli et al., Cell Biol Int 36(1):7-19, 2012) without steroid. Alizarin Red and Alcian-Blue (Sigma-Aldrich, Milano, Italy) stainings were performed. RNA and cDNA were obtained as previously reported (Barboni et al., Cell Transplant. 21(11), 2377–2395, 2012). Real Time for NANOG, SOX2 ,OCT4 stemness genes expression were performed by SensiFast SYBR (Bioline, Aurogene, Rome, Italy) using specific primers (Mattioli et al., Cell Biol Int. 36(1):7-19, 2012).The protocol was: 5 min at 95°C, 30 cycles at 95°C for 15 sec, 60°C for 30 sec, 72°C for 15 sec. Comparative Ct 2-ΔΔC(t) normalization to GAPDH was applied. IHC analyses were carried out for Cytokeratin 8 and αSMA expression as previously reported (Barboni et al. PLoS ONE 7(2): e30974, 2012). Data expressed as mean (±SD), compared by one-way ANOVA followed by Tukey’s test (GraphPad Prism 5). Significant values for P < 0.05. Steroids treated ovine AECs proliferate with significant differences between concentrations. While P4 treated cells showed cuboidal shape and Cytokeratin expression until third passage, CTR and E2 treated cells showed a rapid downregulation of Cytokeratin and increased αSMA expression. oAECs with E2+P4 showed both cell type morphology. Steroids modified stemness genes based on the concentration. 12.5 μM E2, 25μM P4 and 25μM of both E2+P4 treatments maintained higher OCT4, NANOG and SOX2 expressions in treated cells despite their progressive downregulation in the CTR. Moreover, compared to CTR, after Alizarin staining, steroid pretreated cells suffered morphological changes under DM acquiring Alcian Blue-positive chondrogenic-like morphology. AECs stemness properties and plasticity can be modified by prolonged steroidal treatment. These data improve our knowledge, opening new prospective on oAEC use in stem cell-based therapy. Acknowledgments. Research supported by H2020-MSCA ITN EJD-REP BIOTECH 675526

BeWeB: un giovane progetto che compie vent'anni

Il portale BeWeB rappresenta il racconto delle comunità di eredità che esprimono il valore identitario del patrimonio culturale nelle sue diverse tipologie, materiale e immateriale, come riflesso ed espressione dei loro valori, delle conoscenze e tradizioni, in continua evoluzione. I beni ecclesiastici, oltre ad avere un'accezione culturale, storica, artistica, bibliografica, archivistica e patrimoniale, rappresentano anche uno dei luoghi in cui si compie la missione della chiesa. Le diocesi e le parrocchie, nel catalogare i propri beni attraverso un progetto locale di carattere nazionale, hanno investito risorse culturali, umane ed economiche motivate da una prospettiva principalmente legata alla conoscenza, certamente patrimoniale e di tutela, svolgendo l'attività con crescente consapevolezza. Ultimamente questa consapevolezza del dono da custodire e da trasmettere, da usare oggi, è cresciuta, e ormai in quei beni le comunità identificano i motivi della propria identità, un valore di vita e di annuncio

Graphene oxide affects in vitro fertilization outcome by interacting with sperm membrane in an animal model

We realized the exposure of boar spermatozoa to graphene oxide (GO) at concentration of 0.5, 1, 5, 10 and 50 μg/mL in an in vitro system able to promote the capacitation, i.e. the process that allows sperm cells to became fertile. Interestingly, we found that the highest GO concentration (5, 10 and 50 μg/mL) are toxic for spermatozoa, while the lowest ones (0.5 and 1 μg/mL) seem to significantly increase the sperm cells fertilizing ability (p >.05) in an in vitro fertilization experiment. To explain this finding, we investigated the effect of GO on sperm membrane structure (atomic force microscopy) and function (confocal microscopy and flow cytometry, substrate adhesion). As a result, we found that GO is able to interact with spermatozoa membranes and, in particular, it seems to be able to extract the cholesterol, which is a key player in spermatozoa physiology, from plasma membrane of boar spermatozoa incubated under capacitation conditions. In our opinion, these results are very important because they allow identifying either a plausible mechanism of GO toxicity on spermatozoa and new strategies to manage sperm capacitation

Multimodal lung cancer screening using the ITALUNG Biomarker Panel and Low Dose Computed Tomography. Results of the ITALUNG biomarker study

Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1356), in which samples of blood and sputum were analysed for plasma DNA quantification (cut off 5ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71%% and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes