The SIAMS-ED Trial: A National, Independent, Multicentre Study on Cardiometabolic and Hormonal Impairment of Men with Erectile Dysfunction Treated with Vardenafil

Increased cardiovascular risk has been associated with reduced response to proerectile drugs. The Italian Society of Andrology and Sexual Medicine (SIAMS) promoted an independent, multicenter study performed in 604 men (55 ± 12 yrs) suffering from erectile dysfunction (ED) to assess multiple health outcomes and response to 6-month vardenafil challenge in a real-life setting. Overall, 30.8% men had metabolic syndrome. Cardiovascular risk stratification revealed a greater number of ED subjects with moderate risk of a major adverse cardiovascular event than the general population (P < 0.01). Age-adjusted pulse pressure was positively correlated with ED severity and negatively with androgens and waist circumference (P < 0.01). A decline in total testosterone was observed with increasing arterial pulse pressure (P < 0.05), which was not accompanied by compensatory LH rise. Follow-up on 185 men treated with vardenafil in an nonrandomized, open, single-arm trial documented a significant rise in IIEF-5 (delta = 6.1 ± 4.8) that was maintained in men with high cardiovascular risk. Mild adverse events occurred in <5%, with no differences between cardiovascular risk classes. In summary, ED is a frequent symptom in patients with an elevated, but often unknown, risk of future cardiovascular events. Androgens predict vascular resistance in ED patients. Vardenafil's response and safety profile were preserved in subjects with higher cardiovascular risk

Sustained Exendin-4 Secretion through Gene Therapy Targeting Salivary Glands in Two Different Rodent Models of Obesity/Type 2 Diabetes.

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile

Associations between cardiac arrhythmia, incident disability in activities of daily living and physical performance: the ILSA study

Background: Cardiac arrhythmias are common conditions in older people. Unfortunately, there is limited literature on associations between cardiac arrhythmias and physical performance or disability. We therefore aimed to prospectively investigate associations between cardiac arrhythmias and changes in disability and physical performance during 8 years of follow-up, using data from the Italian Longitudinal Study on Aging (ILSA). Methods: Cardiac arrhythmias diagnosis was posed through a screening phase, confirmed by a physician. The onset of disability in activities of daily living (ADL) and the changes in several physical performance tests during follow-up were considered as outcomes. Fully-adjusted and propensity-score Cox Proportional Hazard models and mixed models were used for exploring associations between cardiac arrhythmia and the outcomes of interest. Results: The prevalence of cardiac arrhythmia at baseline was 23.3%. People reporting cardiac arrhythmia at the baseline were significantly older, more frequently male, smokers and reported a higher presence of all medical conditions investigated (hypertension, heart failure, angina, myocardial infarction, diabetes, stroke), but no difference in dementia, Parkinsonism, cognitive or mood disorder. Cardiac arrhythmia at baseline was significantly associated with the incidence of disability in ADL (HR = 1.23; 95%: CI: 1.01–1.50; P = 0.0478 in propensity score analyses; HR = 1.28; 95% CI: 1.01–1.61; P = 0.0401 in fully adjusted models). Cardiac arrhythmia at baseline was also associated with a significant worsening in balance test (P = 0.0436). Conclusions: The presence of cardiac arrhythmia at baseline was associated with a significant higher risk of disability and of worsening in some physical performance tests, particularly those relating to balance. Screening and frequently assessing physical performance in older people affected by cardiac arrhythmia can be important to prevent a loss of physical performance, with further, potential, complications of medical management

Study of radiation damage and substrate resistivity effects from beam test of silicon microstrip detectors using LHC readout electronics

We present the beam test results of single-sided silicon microstrip detectors, with different substrate resistivities. The effects of radiation damage are studied for a detector irradiated to a fluence of 2.4 multiplied by 10**1**4 n/cm**2. The detectors are read out with the APV6 chip, which is compatible with the 40 MHz LHC clock. The performance of different detectors and readout modes are studied in terms of signal-to-noise ratio and efficiency

PHEMTO: the polarimetric high energy modular telescope observatory

Based upon dual focusing techniques, the Polarimetric High-Energy Modular Telescope Observatory (PHEMTO) is designed to have performance several orders of magnitude better than the present hard X-ray instruments, in the 1–600 keV energy range. This, together with its angular resolution of around one arcsecond, and its sensitive polarimetry measurement capability, will give PHEMTO the improvements in scientific performance needed for a mission in the 2050 era in order to study AGN, galactic black holes, neutrons stars, and supernovae. In addition, its high performance will enable the study of the non-thermal processes in galaxy clusters with an unprecedented accuracy.Open access funding provided by Istituto Nazionale di Astrofisica within the CRUI-CARE Agreement

Congenital myopathies: Clinical phenotypes and new diagnostic tools

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Historically, congenital myopathies have been classified on the basis of major morphological features seen on muscle biopsy. However, different genes have now been identified as associated with the various phenotypic and histological expressions of these disorders, and in recent years, because of their unexpectedly wide genetic and clinical heterogeneity, next-generation sequencing has increasingly been used for their diagnosis. We reviewed clinical and genetic forms of congenital myopathy and defined possible strategies to improve cost-effectiveness in histological and imaging diagnosis

Are Compression Stockings an Effective Treatment for Orthostatic Presyncope?

Syncope, or fainting, affects approximately 6.2% of the population, and is associated with significant comorbidity. Many syncopal events occur secondary to excessive venous pooling and capillary filtration in the lower limbs when upright. As such, a common approach to the management of syncope is the use of compression stockings. However, research confirming their efficacy is lacking. We aimed to investigate the effect of graded calf compression stockings on orthostatic tolerance

HIV-1 transmitted drug resistance in newly diagnosed individuals in Italy over the period 2015–21

Background: Transmitted drug resistance (TDR) is still a critical aspect for the management of individuals living with HIV-1. Thus, its evaluation is crucial to optimize HIV care. Methods: Overall, 2386 HIV-1 protease/reverse transcriptase and 1831 integrase sequences from drug-naïve individuals diagnosed in north and central Italy between 2015 and 2021 were analysed. TDR was evaluated over time. Phylogeny was generated by maximum likelihood. Factors associated with TDR were evaluated by logistic regression. Results: Individuals were mainly male (79.1%) and Italian (56.2%), with a median (IQR) age of 38 (30-48). Non-B infected individuals accounted for 44.6% (N = 1065) of the overall population and increased over time (2015-2021, from 42.1% to 51.0%, P = 0.002). TDR prevalence to any class was 8.0% (B subtype 9.5% versus non-B subtypes 6.1%, P = 0.002) and remained almost constant over time. Overall, 300 transmission clusters (TCs) involving 1155 (48.4%) individuals were identified, with a similar proportion in B and non-infected individuals (49.7% versus 46.8%, P = 0.148). A similar prevalence of TDR among individuals in TCs and those out of TCs was found (8.2% versus 7.8%, P = 0.707).By multivariable analysis, subtypes A, F, and CFR02_AG were negatively associated with TDR. No other factors, including being part of TCs, were significantly associated with TDR. Conclusions: Between 2015 and 2021, TDR prevalence in Italy was 8% and remained almost stable over time. Resistant strains were found circulating regardless of being in TCs, but less likely in non-B subtypes. These results highlight the importance of a continuous surveillance of newly diagnosed individuals for evidence of TDR to inform clinical practice

Three-row versus two-row circular staplers for left-sided colorectal anastomosis: a propensity score-matched analysis of the iCral 2 and 3 prospective cohorts

Background: Since most anastomoses after left-sided colorectal resections are performed with a circular stapler, any technological change in stapling devices may influence the incidence of anastomotic adverse events. The aim of the present study was to analyze the effect of a three-row circular stapler on anastomotic leakage and related morbidity after left-sided colorectal resections. Materials and methods: A circular stapled anastomosis was performed in 4255 (50.9%) out of 8359 patients enrolled in two prospective multicenter studies in Italy, and, after exclusion criteria to reduce heterogeneity, 2799 (65.8%) cases were retrospectively analyzed through a 1:1 propensity score-matching model including 20 covariates relative to patient characteristics, to surgery and to perioperative management. Two well-balanced groups of 425 patients each were obtained: group (A) – true population of interest, anastomosis performed with a three-row circular stapler; group (B) – control population, anastomosis performed with a two-row circular stapler. The target of inferences was the average treatment effect in the treated (ATT). The primary endpoints were overall and major anastomotic leakage and overall anastomotic bleeding; the secondary endpoints were overall and major morbidity and mortality rates. The results of multiple logistic regression analyses for the outcomes, including the 20 covariates selected for matching, were presented as odds ratios (OR) and 95% confidence intervals (95% CI). Results: Group A versus group B showed a significantly lower risk of overall anastomotic leakage (2.1 vs. 6.1%; OR 0.33; 95% CI 0.15–0.73; P = 0.006), major anastomotic leakage (2.1 vs. 5.2%; OR 0.39; 95% CI 0.17–0.87; P = 0.022), and major morbidity (3.5 vs. 6.6% events; OR 0.47; 95% CI 0.24–0.91; P = 0.026). Conclusion: The use of three-row circular staplers independently reduced the risk of anastomotic leakage and related morbidity after left-sided colorectal resection. Twenty-five patients were required to avoid one leakage