On the peritidal cycles and their diagenetic evolution in the Lower Jurassic carbonates of the Calcare Massiccio Formation (Central Apennines)

This paper shows the environmental changes and high-frequency cyclicity recorded by Lower Jurassic shallow- water carbonates known as the Calcare Massiccio Formation which crop out in the central Apennines of Italy. Three types of sedimentary cycle bounded by subaerial erosion have been recognized: Type I consists of a shallowing upward cycle with oncoidal floatstones to rudstones passing gradationally up into peloidal packstone alternating with cryptoalgal laminites and often bounded by desiccation cracks and pisolitic-peloidal wackestones indicating a period of subaerial exposure. Type II shows a symmetrical trend in terms of facies arrangement with peloidal packstones and cryptoalgal laminites present both at the base and in the upper portion of the cycle, separated by oncoidal floatstones to rudstones. Type III displays a shallowing upward trend with an initial erosion surface overlain by oncoidal floatstones to rudstones that, in turn, are capped by pisolitic-peloidal wackestones and desiccation sheet cracks. Sheet cracks at the top of cycles formed during the initial phase of subaerial exposure were successively enlarged by dissolution during prolonged subaerial exposure. The following sea-level fall produced dissolution cavities in subtidal facies, while the successive sea-level rise resulted in the precipitation of marine cements in dissolution cavities. Spectral analysis revealed six peaks, five of which are consistent with orbital cycles. While a tectonic control cannot be disregarded, the main signal recorded by the sedimentary succession points toward a main control related to orbital forcing. High frequency sea-level fluctuations also controlled diagenetic processes

Post-rift sequence architecture and stratigraphy in the Oligo-Miocene Sardinia rift (Western Mediterranean Sea)

Rift basins provide important sedimentary archives to reconstruct past tectonic and climatic conditions. Understanding their sedimentary history is, however, largely hampered by the competing influence of tectonic versus climatic forcing. The aim of this study is to comprehend the effects of local to regional tectonic and global climatic/eustatic changes on shallow marine depositional systems in the Sardinia Rift (Western Mediterranean Sea). For this purpose the stratigraphic and depositional relations of a mixed siliciclastic-carbonate ramp at the Porto Torres Basin margin were studied along extensive proximal to distal transects. Three depositional sequences (DS1 to DS3) of late Burdigalian to early Serravallian age have been identified, which are separated by erosional unconformities. Each contains a lower trans- gressive part and an upper regressive part. The former includes shoreface sandstone (DS2) or coral reef (DS3) deposits on the proximal ramp and channelized sheet sandstone (DS1) or basinal mudstone (DS2, DS3) deposits on the distal ramp, typically recording an upsection trend of sediment starvation. The latter is represented by basinward-prograding coralline red algal carbonate wedges due to enhanced shallow water carbonate production rates. In the long term, the depositional evolution from DS1 to DS3 reveals basin margin progradation associated with decreasing siliciclastic supply. Integrated calcareous nannoplankton-foraminiferal-pectinid biostratigraphy links the depositional sequences to third-order sea-level cycles and allows to correlate the erosional unconformities at the top of DS1 and DS2 with the Bur 5/Lan 1 and Lan 2/Ser 1 sequence boundaries. The improved sequence stratigraphic framework enables better regional and global correlations. This shows that rhodalgal carbonate slopes started prograding in the western branch of the Sardinia Rift during the late Burdigalian because (1) of a worldwide bloom of rhodalgal facies, and (2) decreasing tectonic activity at the transition from the syn- rift to the post-rift stage caused a continuous reduction of the siliciclastic sediment input

Glycerophosphoinositol 4-phosphate, a putative endogenous inhibitor of adenylylcyclase.

In a continuous line of rat thyroid cells transformed by the k-ras oncogene (KiKi), the expression of ras-p21 correlates with an increased activity of a phosphoinositide-specific phospholipase A2, which leads to elevated levels of glycerophosphoinositols. In this study we have characterized the biological activities of these compounds. Growth and differentiation in thyroid cells are mainly regulated by the activation of adenylylcyclase. Therefore, we have studied the effects of glycerophosphoinositols on the activity of this enzyme using a normal thyroid cell line (FRTL5). Micromolar concentrations of glycerophosphoinositol 4-phosphate (GroPIns-4-P) caused a approximately 50% inhibition of the adenylylcyclase activity in FRTL5 membranes stimulated by the GTP-binding protein activator fluoroaluminate. Similar concentrations of GroPIns-4-P were detected in KiKi cells but not in the normal FRTL5 line. Micromolar GroPIns-4-P was found to be taken up by intact FRTL5 cells and to induce nearly 50% inhibition of the thyrotropin- and cholera toxin-induced increase in cAMP levels. Similar results were also observed in other cell lines (smooth muscle, pituitary cells, and pneumocytes). GroPIns-4-P inhibited cAMP-dependent cellular functions such as iodide uptake and thymidine incorporation in FRTL5 cells when stimulated by thyrotropin and cholera toxin but not when induced by forskolin. These results are consistent with GroPIns-4-P exerting an inhibitory effect on the GTP-binding protein that stimulates adenylycyclase. We propose that GroPIns-4-P might mediate a mechanism of cross-talk between adenylylcyclase and phospholipase A2 in thyroid as well as in other cell systems

Characterization of power transistors as high dose dosimeters

A bipolar transistor, previously investigated as a possible radiation dosimeter and tested under industrial irradiation conditions in high-activity gamma and high-energy, high-power electron beam facilities has been subjected to stability test in order to understand its behaviour and help to improve its performances. Charge carrier lifetime was measured for several sets of transistors which were then irradiated with various doses (3-60 kGy): seven sets with Co-60 gamma rays and eight with a 10MeV electron beam. After irradiation all the transistors were measured and each set was divided into three groups: one group was left untreated, the second group was heated at 100 degrees C for 30 minutes and the third group was heated at 150 degrees C for 30 minutes, for testing the stability of the lifetime. Our data showed that heat treatment quite successfully eliminates post-irradiation changes in the response. Response measurements of the irradiated transistors, heat-treated and untreated, were carried out at room temperature over several weeks after irradiation to establish post-irradiation stability and assess if these transistors could be used for recording dose history. Calibration curves in the range 3-60 kGy for the thermally treated and untreated devices are presented. Dependence of the response of the transistors on the temperature of the measurements in the range 20-50 degrees C is reported

Danon disease in a Sardinian family: different aspects of the same mutation-a case report

Background Danon disease (DD) is a rare X-linked disorder due to mutations in the lysosome-associated membrane protein 2 gene. It is characterized by a clinical triad of hypertrophic cardiomyopathy, skeletal myopathy, and a variable degree of intellectual disability. Case summary In this case series, we describe a mother and her son affected by DD, highlighting consistent clinical severity despite the expected variability related to gender. The mother (Case 1) presented isolated cardiac involvement, with an arrhythmogenic phenotype that evolved into severe heart failure requiring heart transplantation (HT). Danon disease was diagnosed 1 year after this event. Her son (Case 2) showed an earlier age onset of symptoms with complete atrioventricular block and fast progression of cardiac disease. Diagnosis was established 2 years after clinical presentation. He is currently listed for HT. Discussion In both of our patients, diagnostic delay was extremely long and could have been avoided by emphasizing the relevant clinical red flags. Patients affected by DD may present clinical heterogeneity in terms of natural history, age of onset, and cardiac and extracardiac involvement, even in the same family. Early diagnosis that phenotypic sex differences may impact is a crucial factor in managing patients with DD. Considering the rapid progression of cardiac disease and the poor prognosis, early diagnosis is important and close surveillance should be mandatory during follow-up

650 Quality of life of patients with end stage heart failure treated with left ventricular assist devices

Abstract Aims Nowadays continuous flow left ventricular assist devices (LVAD) have become a reality for patients with end-stage heart failure (HF) who are failing maximal medical treatment, both eligible or not for heart transplantation. LVADs have demonstrated to improve functional capacity and clinical outcomes, including breathing and activity tolerance, but the impact on patients quality of life (QoL) is still a vexed and open question. Moreover, the device implantation actually requires significant life style changes, high motivation and adherence to treatment, both for patients and their caregivers. Patients must learn to live with the device and to interface with the controller and batteries system, adjusting everyday life's activities to the device presence. The purpose of our study is to evaluate how the implantation of HeartMate 3™ impact on patients-related QoL and clinical outcomes, compared with general population and other chronic diseases. Methods and results Eight patients (pts) with a diagnosis of end-stage HF were implanted with the HeartMate 3™ LVAD from May 2017 to October 2019 in the Cardiac Surgery Unit of Brotzu Hospital. During a follow-up visit (28.7 ± 11.9 months after surgery), the 7 pts presenting were assessed with two questionnaires, the SF-12 and EuroQoL-5D, in order to evaluate improvement of quality of life compared with clinical presentation. Afterwards we compared the average SF-12 total result with 28 controls from general population and with other important chronic diseases. The analysis of SF-12 questionnaires showed an average of 28.00 ± 8.98 (VN: 12–47) as total score, 11.7 ± 3.4 (VN: 6–20) as physical health component score and 16.2 ± 6.5 (VN: 6–27) as mental health component score. These findings, though within the range of 'normality', are closer to the lower scores and show the negative impact of LVAD in everyday patients-related quality of life. Comparing the NYHA functional class with these results, we found a statistically significant negative linear correlation for both total (−0.80, P = 0.03) and mental health component scores (−0.75, P = 0.049). Average total score of our pts significatively differs compared with 28 controls of general population (28.00 ± 8.98 vs. 38.64 ± 6.80, P = 0.014), as well as compared with other chronic diseases like Wilson's disease (P < 0.001), celiac disease (P < 0.001), obsessive-compulsive disorder (P < 0.001), panic disorder (P < 0.001), major depressive disorder (P = 0.009), multiple sclerosis (P < 0.011), food disorders (P = 0.023), and carotid atherosclerosis (P = 0.049). The EuroQoL-5D questionnaire investigates five particular 'dimensions' of the subjectively perceived health-related quality of life (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and shows similar. We found a poor average score at Visual Analogue Scale (58.5 ± 18.86) and a statistically significant negative linear correlation with NYHA functional class (−0.76, P = 0.046). The 42.86% referred no pain or discomfort and in the other four dimensions most of them reported 'moderate limitations', both physical or mental, especially for self-care domain (85.71%), as inevitable result of the device's size. Conclusions LVAD can improve clinical outcomes and functional capacity of carefully select pts with end-stage HF, but the complications encountered during mechanical support and the lifestyle changes required can affect negatively patients well-being. Many studies have shown that most patients experience significant improvement even in QoL's perception but for others the device have a negative impact on many aspects of normal daily living as well as emotional, mental and social functioning. Our study confirms this conflicting results: physical related-quality of life improves after LVAD implantation but emotional and psychological distress may persist, especially during long-term support, as a result of complications, co-morbidities and personal's attitudes, values and way of life

Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on the simplification of the drug regimen for secondary cardiovascular prevention

: The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socio-economic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening