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In recent years, the topic of motor inverterization has become increasingly popular as it offers numerous benefits in terms of energy efficiency and control. Central to this topic is the development of gate drivers, which are critical components in controlling the switching of power devices in the inverter-leg. The introduction of high voltage integrated circuits (HVICs) has greatly simplified the inverter system, but has also brought in new challenges in terms of communication between different voltage domains, each isolated from each other up to several hundreds volts. In this paper, the characterization of an integrated high voltage capacitance in silicon-on-insulator (SOI) technology placed between two voltage domains is presented, allowing for a bilateral form of communication at the cost of withstanding high voltage at its terminals. The measurement of this element required a dedicated circuital structure, and the value of the capacitance was measured to be around 127 fF and its breakdown voltage at around 1800 V.

Purpose: Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients’ quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL. Methods: One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20–85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression). Results: A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL. Conclusions: We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, an increasing number of chilblain-like lesions (ChLL) have been increasingly reported worldwide. To date, the causal link between ChLL and SARS-CoV-2 infection has not been unequivocally established. Methods: In this case series, we present demographic, clinical, laboratory, and histopathological information regarding 27 young patients with a clinical diagnosis of ChLL who referred to the Dermatology Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, from 1 April 2020 to 1 June 2020. Results: The mean age was 14.2 years, and 21 patients (78%) experienced mild systemic symptoms a median of 28 days before the onset of cutaneous lesions. ChLL mostly involved the feet (20 patients – 74%). Among acral lesions, we identified three different clinical patterns: (i) chilblains in 20 patients (74%); (ii) fixed erythematous macules in 4 children (15%); (iii) erythrocyanosis in 3 female patients (11%). Blood examinations and viral serologies, including parvovirus B19, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and coxsackievirus were normal in all. Three patients (11%) underwent nasopharyngeal swab for RT-PCR for SARS-CoV-2 showing only 1 positive. Histopathological examinations of 7 skin biopsies confirmed the clinical diagnosis of chilblains; vessel thrombi were observed only in 1 case. Our findings failed to demonstrate the direct presence of SARS-CoV-2 RNA in skin biopsies, both with real-time polymerase chain reaction (RT-PCR) and RNAscope in situ hybridization (ISH). Limitations: Limited number of cases, unavailability of laboratory confirmation of COVID-19 in all patients, potential methodological weakness, and latency of skin biopsies in comparison to cutaneous lesions onset. Conclusions: These observations may support the hypothesis of an inflammatory pathogenesis rather than the presence of peripheral viral particles. Although, we could not exclude an early phase of viral end

An electrostatic discharge (ESD)-protected one-time-programmable (OTP) memory front-end circuit, for high-voltage (HV) applications, designed and manufactured in silicon-on-insulator (SOI) technology, is presented. The SOI technology meets HV functional-isolation and level-shifting requirements but is not suitable for advanced analog circuits. The presented OTP memory is discussed as an introduction to digital programmability in the considered technology. The memory element consists of an antifuse type structure and is implemented using a 5-V nMOS with L=1µm and W=1.2µm. The cell memory allows for significant area and power savings in the adopted HV technology. Conditions for this require that an efficient ESD protection will guarantee safe operation, even in the presence of a small and fragile on-chip element whose undesired burning would compromise the programming mechanism, and consequently the reliability, of the circuit. Details about the circuit design implementation of the front-end circuit for both read and write circuits and ESD protection are described with experimental results validating the proposed implementation.

Background: First-line therapy of Cushing disease (CD) is transsphenoidal surgery (TSS) aimed to obtain a complete removal of the pituitary adenoma and remission of disease. Purpose: To analyse the surgical outcome of patients with CD who underwent TSS in our Centre. Methods: Retrospective analysis on patients with CD who underwent TSS between 1990 and 2016. Results: We analysed 102 TSS that included: 84 first TSS and 18 second and third TSS. The overall remission rate after surgery was 76.5%, with a significant higher percentage of remitted patients after the first TSS compared to the subsequent TSS (82% vs 50%, p = 0.014). The remission after the first TSS was significantly higher when performed by a dedicated surgical team (DST) (89.8% vs 71% p = 0.04) and when the immunohistochemical examination confirmed the adrenocorticotropic adenoma (87% vs 55%, p = 0.04). Neuroradiological findings influenced the surgical outcome in a non-significant manner. Post-TSS complications were reported in 32 patients, with no significant variation when TSS was performed by DST. In case of reintervention, remission of disease was obtained in 72.7% of microadenoma, while no remitted patients were observed in case of macroadenomas. The DST did not significantly improve the outcome. Conclusion: Cushing disease is characterized by a broad spectrum of neuroradiological presentation. Despite the availability of a DST make the TSS a safe and effective first-line treatment among all these patients, a precise pre-treatment evaluation is needed in order to define the aim of neurosurgery and to schedule the management of recurrent disease.

Data on the vertical transmission rate of COVID-19 in pregnancy are limited, although data reporting mother-fetal transmission in the second trimester of pregnancy are controversial. We described a case of second-trimester twin stillbirth in a woman with SARS-CoV-2 infection in which placental and fetal markers of infection were detected, despite the absence of respiratory syndrome. The patient developed clinical chorioamnionitis and spontaneously delivered 2 stillborn infants. Placental histology and immunohistochemistry demonstrated SARS-CoV-2 infection mostly within the syncytiotrophoblast, and fetal autopsy showed the development of interstitial pneumonia. Our findings demonstrated that in utero vertical transmission is possible in asymptomatic pregnant women with SARS-CoV-2 infection and that infection can lead to severe morbidity in the second trimester of pregnancy.

Al giorno d'oggi il consumo mondiale di energia elettrica è in continuo aumento e più della metà dell'elettricità prodotta è consumata dai motori elettrici. Per far fronte a questo aumento, l'uso di motori a velocità variabile è fortemente incentivato nella gran parte dei paesi dalle normative sull'efficienza energetica. Questi motori sono in grado di consumare solo la quantità di elettricità necessaria. Questo è possibile grazie all’inverterizzazione: i motori a velocità variabile sono pilotati da switch di potenza collegati nella configurazione inverter-leg. Per fornire la corrente richiesta dal motore, gli switch di potenza vengono accesi e spenti alternativamente dal gate driver per generare un segnale modulato ad ampiezza di impulso nei nodi di fase del motore. I gate driver sono generalmente progettati per avere un singolo livello di corrente di uscita che viene utilizzato per caricare/scaricare le capacità parassite sulla gate dei power switch per accenderli/spegnerli. Un sistema di questo genere è molto efficiente, ma la dissipazione, anche se piccola, è sempre da considerare. Negli ultimi anni, la tecnologia superjunction (SJ) ha rivoluzionato l'industria dei dispositivi di potenza ad alta tensione migliorando il rapporto prestazioni/costi della conversione di potenza. I dispositivi SJ sono in grado di superare il Silicon Limit: il tradeoff tra tensione di breakdown e resistenza di stato on. Tuttavia, sono caratterizzati da una capacità di Miller non lineare, che fa sì che l'evento di switching inizi con dV/dt molto elevati e termini con un lunga slow-tail nelle ultime decine di volt. In un gate driver standard, il valore della corrente di gate io+ viene scelto come compromesso tra due vincoli opposti: limitare la dissipazione di potenza con un dV/dt veloce e soddisfare i vincoli di emissione condotta e radiata con un dV/dt lento. Con i dispositivi SJ non è quindi possibile usare un valore fisso di io+. Per usare i power switch in modo effi, Nowadays the world consumption of electrical energy is continuously increasing. More than an half of the produced electricity is consumed by electric motors. In order to cope with the increase in electricity consumption, the use of variable speed motor drives is promoted by energy efficiency regulations in most countries. These motors are able to consume only as much electricity as the application actually needs. They can do this by exploiting inverterization: variable speed drive motors are driven by power semiconductor switches connected in the inverter-leg configuration. They are alternatively switched on and off by the gate driver to generate a pulse width modulated signal on motor phase nodes used to provide the required current to the load. High voltage gate drivers are usually designed to have one single output current level used to charge/discharge the parasitic gate of external power switches to turn them on and off. Driving with a switching system is very efficient, but the dissipation, even if small, is always present and must be taken into account. In recent years, superjunction (SJ) technology has revolutionized the industry of high voltage power devices significantly improving the overall performance/cost ratio of power conversion. SJ devices are able to overcome the trade-off between breakdown voltage and on resistance, better known as the Silicon Limit. However, they are characterized by a non linear Miller capacitance, which causes the switching speed transient to start with very high dV/dt and to finish with a long slow-tail in the last few volts. In standard gate driver, the io+ driving capability is selected to find the best compromise between two opposite constraints: limiting the power dissipation with a fast dV/dt while satisfying conducted and radiated emission constraints with a slow dV/dt. With SJ devices it is not possible to meet this trade-off by simply selecting a fixed io+ value. To drive power switches with high efficiency a new drivi

Background: Resistant hypertension is independently associated with an increased risk of death in the general hypertensive population. We assessed whether resistant hypertension is an independent predictor of all-cause mortality in individuals with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Methods: On 31 October 2015, vital status information was retrieved for 15,656 of the 15,773 participants enrolled in 2006-2008. Based on baseline blood pressure (BP) values and treatment, participants were categorized as normotensive, untreated hypertensive, controlled hypertensive (i.e., on-target with < 3 drugs), uncontrolled hypertensive (i.e., not on-target with 1-2 drugs), or resistant hypertensive (i.e., uncontrolled with > 3 drugs or controlled with > 4 drugs). Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the association with all-cause mortality. Results: Using the 130/80 mmHg targets for categorization, crude mortality rates and Kaplan-Meier estimates were highest among resistant hypertension participants, especially those with controlled resistant hypertension. As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, including individuals with controlled hypertension (hazard ratio 0.81 [95% confidence interval 0.74-0.89], P < 0.0001), but became progressively similar between resistant and controlled hypertension after adjustment for cardiovascular risk factors and complications/comorbidities. Also when compared with controlled resistant hypertension, mortality risk was significantly lower for all the other groups, including controlled hypertension, even after adjusting for cardiovascular risk factors (0.77 [0.63-0.95], P = 0.012), but not for complications/comorbidities (0.88 [0.72-1.08], P = 0.216). BP was well below target in the controlled hypertensive groups (resistant and non-resistant) and values < 120/7

Purpose: Arthropathy is a common and disabling complication of acromegaly. Since in this condition radiological findings rarely correspond to functional impairment, we elected to quantify in a large cohort of acromegalic patients: the degree of motor disability compared with data from general population, the impact of joint involvement on quality of life and work productivity, and to look for associated factors. Methods: In 211 acromegalic patients, 131 with controlled disease and 80 with active disease, eight validated scales were used to evaluate the (i) prevalence and distribution of arthropathy, (ii) degree of motor disability and joint symptoms (VAS, AIMS symptoms and WOMAC), (iii) quality of life (AcroQoL and PASQ) and work capability (WPAI:GH) as consequences of joint complications. Results: Using the WOMAC questionnaire, for which population based normative values are available, a significantly higher prevalence and severity of motor disability was detected in acromegalics compared to the general population from literature. The results provided by the different questionnaires turned out to be highly concordant. All measures of motor disability correlated both with impaired quality of life and motor disability and were worse in females and in patients with higher BMI. Conclusions: The questionnaires VAS, AIMS symptoms, and WOMAC (this latter both as a whole and with its functionality subscale), with their scores, proved to be the most adequate tools to evaluate motor disability and its consequences on both quality of life and work productivity in acromegaly. Female gender and higher BMI are associated with worse articular symptoms.

Background: Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133 + cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function. Methods: In the phase I "Endocavitary Injection of Bone Marrow Derived CD133 + Cells in Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction ≤ 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations. Results: Patients were treated safely with a mean number of 6.57 ± 3.45 × 10 6 ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 ± 8.6 to 13.8 ± 7.8, p = 0.05) and difference scores (from 12.0 ± 5.3 to 6.1 ± 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 ± 2.2 to 4.0 ± 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p ≤ 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = - 0.79, p = 0.01) and IL-6 (r = - 0.76, p = 0.02). Conclusion: Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction

Background: Vertebral fractures (VFs) are a frequent complication of acromegaly, but no studies have been so far published on effectiveness of antiosteoporotic drugs in this clinical setting. Objective: To evaluate whether in real-life clinical practice bone active drugs may reduce the risk of VFs in patients with active or controlled acromegaly. Study design: Retrospective, longitudinal study including 9 tertiary care endocrine units. Patients and methods: Two hundred and forty-eight patients with acromegaly (104 males; mean age 56.00 ± 13.60 years) were evaluated for prevalent and incident VFs by quantitative morphometric approach. Bone active agents were used in 52 patients (20.97%) and the median period of follow-up was 48 months (range 12-132). Results: During the follow-up, 65 patients (26.21%) developed incident VFs in relationship with pre-existing VFs (odds ratio [OR] 3.75; P < .001), duration of active acromegaly (OR 1.01; P = .04), active acromegaly at the study entry (OR 2.48; P = .007), and treated hypoadrenalism (OR 2.50; P = .005). In the entire population, treatment with bone active drugs did not have a significant effect on incident VFs (P = .82). However, in a sensitive analysis restricted to patients with active acromegaly at study entry (111 cases), treatment with bone active drugs was associated with a lower risk of incident VFs (OR 0.11; P = .004), independently of prevalent VFs (OR 7.65; P < .001) and treated hypoadrenalism (OR 3.86; P = .007). Conclusions: Bone active drugs may prevent VFs in patients with active acromegaly.