Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Sex differences in cardiovascular disease (CVD) are often recognized from experimental and clinical studies examining the prevalence, manifestations, and response to therapies. Compared to age-matched men, women tend to have reduced CV risk and a better prognosis in the premenopausal period. However, with menopause, this risk increases exponentially, surpassing that of men. Although several mechanisms have been provided, including sex hormones, an emerging role in these sex differences has been suggested for β-adrenergic receptor (β-AR) signaling. Importantly, β-ARs are the most important G protein-coupled receptors (GPCRs), expressed in almost all the cell types of the CV system, and involved in physiological and pathophysiological processes. Consistent with their role, for decades, βARs have been considered the first targets for rational drug design to fight CVDs. Of note, β-ARs are seemingly associated with different CV outcomes in females compared with males. In addition, even if there is a critical inverse correlation between β-AR responsiveness and aging, it has been reported that gender is crucially involved in this age-related effect. This review will discuss how β-ARs impact the CV risk and response to anti-CVD therapies, also concerning sex and age. Further, we will explore how estrogens impact β-AR signaling in women

The seismogenic structure of the 2013-2014 Matese seismic sequence, Southern Italy: implication for the geometry of the Apennines active extensional belt

Seismological, geological and geodetic data have been integrated to characterize the seismogenic structure of the late 2013-early 2014 moderate energy (maximum local magnitude M-Lmax = 4.9) seismic sequence that struck the interior of the Matese Massif, part of the Southern Apennines active extensional belt. The sequence, heralded by a M-L = 2.7 foreshock, was characterized by two main shocks with M-L = 4.9 and M-L = 4.2, respectively, which occurred at a depth of similar to 17-18 km. The sequence was confined in the 10-20 km depth range, significantly deeper than the 1997-1998 sequence which occurred fewkm away on the northeastern side of the massif above similar to 15 km depth. The depth distribution of the 2013-14 sequence is almost continuous, albeit a deeper (16-19 km) and a shallower (11-15 km) group of events can be distinguished, the former including the main shocks and the foreshock. The epicentral distribution formed a similar to 10 km long NNW-SSE trending alignment, which almost parallels the surface trace of late Pliocene-Quaternary southwest-dipping normal faults with a poor evidence of current geological and geodetic deformation. We built an upper crustal model profile for the eastern Matese massif through integration of geological data, oil exploration well logs and seismic tomographic images. Projection of hypocentres on the profile suggests that the seismogenic volume falls mostly within the crystalline crust and subordinately within the Mesozoic sedimentary cover of Apulia, the underthrust foreland of the Southern Apennines fold and thrust belt. Geological data and the regional macroseismic field of the sequence suggest that the southwest-dipping nodal plane of the main shocks represents the rupture surface that we refer to here as the Matese fault. The major lithological discontinuity between crystalline and sedimentary rocks of Apulia likely confined upward the rupture extent of the Matese fault. Repeated coseismic failure represented by the deeper group of events in the sequence, activated in a passive fashion the overlying similar to 11-15 km deep section of the upper crustal normal faults. We consider the southwest-dipping Matese fault representative of a poorly known type of seismogenic structures in the Southern Apennines, where extensional seismogenesis and geodetic strain accumulation occur more frequently on NE-dipping, shallower-rooted faults. This is the case of the Boiano Basin fault located on the northern side of the massif, to which the 1997-1998 sequence is related. The close proximity of the two types of seismogenic faults at the Matese Massif is related to the complex crustal architecture generated by the Pliocene-early Pleistocene contractional and transpressional tectonics

Relationship between COVID-19 Mortality, Hospital Beds, and Primary Care by Italian Regions: A Lesson for the Future

One of the characteristics of the SARS-CoV-2 infection in Italy is the significant regional difference in terms of lethality and mortality. These geographical variances were clear in the first wave and confirmed in the second one as well. The study aimed to analyze the correlation between regional differences in COVID-19 mortality and different regional care models, by retrospectively analyzing the association between the Italian COVID-19 deaths and the number of hospital beds, long-term care facilities, general practitioners (GPs), and the health expenditure per capita. The period considered was from 1 March 2020 to 1 March 2021. The number of hospital beds (p < 0.0001) and the number of GPs (p = 0.0094) significantly predicted the COVID-19 death rate. The Italian regions with a higher number of hospital beds and a lower number of GPs showed a higher number of deaths. Multivariate analyses confirmed the results. The Italian regions with a higher amount of centralized healthcare, as represented by the number of hospital beds, experienced a higher number of deaths, while the regions with greater community support, as exemplified by the number of the GPs, faced higher survival. These results suggest the need for a change in the current healthcare system organization

Towards a monitoring system of the sea state based on microseism and machine learning

In this work, we exploited the ubiquitous seismic noise generated by energy transfer from the sea to the solid Earth (called microseism) to infer the significant wave height data, with the aim of developing a microseism-based monitoring system of the Sicily Channel. We used a combined approach based on statistical analysis and machine learning by using seismic and sea state data (provided by the hindcast maps), recorded between 2018 and 2021.Through spectral and amplitude analysis, we observed that microseism was influenced by the conditions of the seas surrounding Sicily. Correlation analysis demonstrates that microseism mostly originates from sources located up to 400 km from the coastlines. Moreover, employing machine learning algorithms, we successfully reconstruct spatial and temporal sea wave distributions using microseism data. Among the tested methods, the Random Forest algorithm yields the best results, with an R2 value of 0.89 and a mean prediction error of about 0.21 m

Pressurization and depressurization phases inside the plumbing system of Mount Etna volcano: Evidence from a multiparametric approach

During 2013 Mount Etna volcano experienced intense eruptive activity at the summit craters, foremost at the New Southeast Crater and to a minor degree at the Voragine and Bocca Nuova (BN), which took place in two cycles, February-April and September-December. In this work, we mainly focus on the period between these cycles, applying a multiparametric approach. The period from the end of April to 5 September showed a gradual increase in the amplitude of long-period (LP) events and volcanic tremor, a slight inflation testified by both tilt and GPS data, and a CO2 flux increase. Such variations were interpreted as due to a gradual pressurization of the plumbing system, from the shallowest part, where LP and volcanic tremor are located, down to about 3-9km below sea level, pressure source depths obtained by both geodetic and CO2 data. On 5 September, at the same time as a large explosion at BN, we observed an instantaneous variation of the aforementioned signals (decrease in amplitude of LP events and volcanic tremor, slight deflation, and CO2 flux decrease) and the activation of a new infrasonic source located at BN. In the light of it, the BN explosion probably caused the instantaneous end of the pressurization, and the opening of a new vent at BN, that has become a new steady source of infrasonic events. This apparently slight change in the plumbing system also led to the gradual resumption of activity at the New Southeast Crater, culminating with the second lava fountain cycle of 2013

Risk factors for liver decompensation and hcc in hcv-cirrhotic patients after daas: A multicenter prospective study

Background: Prospective studies on predictors of liver-related events in cirrhotic subjects achieving SVR after DAAs are lacking. Methods: We prospectively enrolled HCV cirrhotic patients in four Italian centers between November 2015 and October 2017. SVR and no-SVR cases were compared according to the presence or absence of liver-related events during a 24-month follow-up. Independent predictors of liver-related events were evaluated by Cox regression analysis. Results: A total of 706 subjects started DAAs therapy. SVR was confirmed in 687 (97.3%). A total of 61 subjects (8.9%) in the SVR group and 5 (26.3%) in the no-SVR group had liver-related events (p < 0.03). The incidence rate x 100 p/y was 1.6 for HCC, 1.7 for any liver decompensation, and 0.5 for hepatic death. Baseline liver stiffness (LSM) ≥ 20 kPa (HR 4.0; 95% CI 1.1–14.1) and genotype different from 1 (HR 7.5; 95% CI 2.1–27.3) were both independent predictors of liver decompensation. Baseline LSM > 20 KPa (HR 7.2; 95% CI 1.9–26.7) was the sole independent predictor of HCC. A decrease in liver stiffness (Delta LSM) by at least 20% at the end of follow-up was not associated with a decreased risk of liver-related events. Conclusion: Baseline LSM ≥ 20 kPa identifies HCV cirrhotic subjects at higher risk of liver-related events after SVR

Take a picture! The role of visual methods in understanding psychiatric patient's everyday life

BACKGROUND AND AIM: Understanding the patient's experience of mental illness can foster better support for this population and greater partnership with healthcare professionals. This study aims to explore the application of visual methods in the psychiatric field and, in particular, the experience of people suffering from psychotic disorders because it is still an open question that has not been only partially empirically examined. METHODS: This qualitative study was conducted using two visual methods (auto-photography and photo-elicitation) associated with the narrative that emerged from an unstructured interview, in a clinical setting of adult Mental Health in Italy, between October 2019 and February 2020. A total of 5 patients and 5 corresponding referring healthcare professionals were identified and enrolled.  Patients were asked to produce photographs following 4 thematic areas: "Fun", "Time", "Something indispensable", "Place where I feel good". RESULTS: A total of 85 photographs were produced. Visual methods have proved to be a useful technique in qualitative research in the area of adult psychiatry. From the interviews, it emerged that visual methods have allowed psychotic patients to use a new language to be able to communicate their emotions. CONCLUSIONS: The healthcare professionals involved also confirm the potential of this tool which, when combined with the traditional interview, is able to deepen the patient's knowledge by overcoming the verbal barriers that often make it difficult to reconstruct the individual experience of illness

β-adrenergic receptors and G protein-coupled receptor kinase-2 in Alzheimer's disease: a new paradigm for prognosis and therapy?

Alzheimer's disease (AD) is a devastating form of dementia that imposes a severe burden on health systems and society. Although several aspects of AD pathogenesis have been elucidated over the last few decades, many questions still need to be addressed. In fact, currently available medications only provide symptomatic improvement in patients with AD without affecting disease progression. The β-adrenergic receptor (β-AR) system can be considered a possible target that deserves further exploration in AD. The central noradrenergic system undergoes substantial changes in the course of AD and β-ARs have been implicated not only in amyloid formation in AD brain but also in amyloid-induced neurotoxicity. Moreover, clinical evidence suggests a protective role of β-AR blockers on AD onset. In addition to that, post-receptor components of β-AR signaling seem to have a role in AD pathogenesis. In particular, the G protein coupled receptor kinase 2, responsible for β-AR desensitization and downregulation, mediates amyloid-induced β-AR dysfunction in neurons, and its levels in circulating lymphocytes of AD patients are increased and inversely correlated with patient's cognitive status. Therefore, there is an urgent need to gain further insight on the role of the adrenergic system components in AD pathogenesis in order to translate preclinical and clinical knowledge to more efficacious prognostic and therapeutic strategies