Conductance quantization in etched Si/SiGe quantum point contacts

We fabricated strongly confined Schottky-gated quantum point contacts by etching Si/SiGe heterostructures and observed intriguing conductance quantization in units of approximately 1e2/h. Non-linear conductance measurements were performed depleting the quantum point contacts at fixed mode-energy separation. We report evidences of the formation of a half 1e2/h plateau, supporting the speculation that adiabatic transmission occurs through 1D modes with complete removal of valley and spin degeneracies.Comment: to appear in Physical Review

Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension

BACKGROUND: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to evaluate the incremental prognostic value of echocardiography of the RV and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients. METHODS: One hundred-thirty treatment-naïve IPAH patients were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-minute walk distance plus an increase in functional class, or non elective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done. RESULTS: During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (Model-1). With addition of echocardiographic and CPET variables (Model-2), peak O2 pulse (peak VO2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (AUC: 0.81 vs 0.66, respectively; p=0.005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC+low O2 pulse showed 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk -RR- of 41.1 and 25.3, respectively), compared with high RVFAC+high O2 pulse (p=0.0001). CONCLUSIONS: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration

Measuring knowledge, attitudes and behavior of nurses in medication management. Cross-cultural comparisons in Italy and Malta

Medication errors are one of the most common causes of negative events affecting patient safety all over the world.  Scientific literature divides the factors that contribute to the occurrence of harmful events into factors related to the characteristics of the healthcare workers and factors related to the organization of the drug management process. The aim of the study was to examine the knowledge, attitudes and behaviours related to medication errors among Italian and Maltese nurses

Quantitative assessment of diffuse myocardial fibrosis in II-type diabetes mellitus patients using T1 mapping technique: preliminary data

In diabetic cardiomyopathy (DCM), ventricular remodelling consists in a progressive impairment of myocardial contraction (evolving from diastolic to combined diastolic-systolic dysfunction) occurring regardless of ischemic heart disease, hypertension or other macrovascular complications, which ultimately leads to heart failure. Early stages of DCM are asymptomatic and characterised by initial contractile disfunction and various degree of myocardial fibrosis, that may not be recognised by traditional cardiology tests. Our purpose was to detect myocardial fibrotic infiltration in DM-II patients by using T1-mapping technique with extracellular volume fraction (ECV) measurement

Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non-palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non-palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non-palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non-neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6-97.0) and 85.5% specificity (95% CI 75.0-92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9-98.5) and 87.1% specificity (95% CI 70.2-96.4) in discriminating neoplasms from non-neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non-neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non-neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2 = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8-92.0) and 79.1% specific (95% CI 68.3-88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7-69.9) and 100% specific (95% CI 88.8-100) in discriminating non-neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non-neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven

Soliton-like Spin State in the A-like Phase of 3He in Anisotropic Aerogel

We have found a new stable spin state in the A-like phase of superfluid 3He confined to intrinsically anisotropic aerogel. The state can be formed by radiofrequency excitation applied while cooling through the superfluid transition temperature and its NMR properties are different from the standard A-like phase obtained in the limit of very small excitation. It is possible that this new state is formed by textural domain walls pinned by aerogel.Comment: 9 pages, 3 figures. Submitted to J. of Low Tem. Phys. (QFS2007 Proceedings

Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers.

Background: Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare. Case series: The present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient's performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions. Conclusion: In our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs' patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release

Are Markers of Systemic Inflammatory Response Useful in the Management of Patients With Neuroendocrine Neoplasms?

Given the increasing incidence of neuroendocrine neoplasms (NENs) over the past few decades, a more comprehensive knowledge of their pathophysiological bases and the identification of innovative NEN biomarkers represents an urgent unmet need. There is still little advance in the early diagnosis and management of these tumors, due to the lack of sensible and specific markers with prognostic value and ability to early detect the response to treatment. Chronic systemic inflammation is a predisposing factor for multiple cancer hallmarks, as cancer proliferation, progression and immune-evading. Therefore, the relevance of inflammatory biomarkers has been identified as critical in several types of tumours, including NENs. A bidirectional relationship between chronic inflammation and development of NENs has been reported. Neuroendocrine cells can be over-stimulated by chronic inflammation, leading to hyperplasia and neoplastic transformation. As the modulation of inflammatory response represents a therapeutic target, inflammatory markers could represent a promising new key tool to be applied in the diagnosis, the prediction of response to treatment and also as prognostic biomarkers in NENs field. The present review provides an overview of the pre-clinical and clinical data relating the potentially usefulness of circulating inflammatory markers: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), cytokines and tissue inflammatory markers (PD-1/PD-L1), in the management of NENs. (1) NLR and PLR have both demonstrated to be promising and simple to acquire biomarkers in patients with advanced cancer, including NEN. To date, in the context of NENs, the prognostic role of NLR and PLR has been confirmed in 15 and 4 studies, respectively. However, the threshold value, both for NLR and PLR, still remains not defined. (2) Cytokines seem to play a central role in NENs tumorigenesis. In particular, IL-8 levels seems to be a good predictive marker of response to anti-angiogenic treatments. (3) PD-1 and PD-L1 expression on tumour cells and on TILs, have demonstrated to be promising predictive and prognostic biomarkers in NENs. Unfortunately, these two markers have not been validated so far and further studies are needed to establish their indications and utility

Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection

A pandemic outbreak of COVID-19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, "cytokines storm", that causes the systemic complications of COVID-19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti-inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID-19 disease. We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own "silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial)". The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID-19 in developing countries

Infodemiological patterns in searching medication errors: Relationship with risk management and shift work

INTRODUCTION: Western world health care systems have been trying to improve their efficiency and effectiveness in order to respond properly to population aging and non-communicable diseases epidemic. Treatment of the elderly population is becoming complex due to the high number of prescribed drugs because of multimorbidity. Errors in drugs administration in different health care related settings are an actual important issue due to different causes. Aim of this observational study is to measure the online interest in seeking medication errors information related to risk management and shift work. MATERIALS AND METHODS: We investigated Google Trends® for popular search relating to medication errors, risk management and shift work. Relative search volumes (RSVs) were evaluated from 2008 to 2018. A comparison between RSV curves related to medication errors, risk management and shift work was carried out. Then, we compared the world to Italian search. RESULTS: RSVs were persistently higher for risk management than for medication errors (mean RSVs 069 vs. 48%) and RSVs were stably higher for medication errors than shift work (mean RSVs 48 vs. 22%). In Italy, RSVs were much lower compared to the rest of the world, and RSVs for medication errors during the study period were negligible. Mean RSVs for risk management and shift work were 3 and 25%, respectively. RSVs related to medication errors and clinical risk management were correlated (r=0.520, p<0.0001). CONCLUSIONS: Google Trends® search query volumes related to medication errors, risk management and shift work are different. RSVs for risk management are higher, and they are correlated with medication errors. Also, shift work search appears to be lower. These results should be interpreted in order to correctly evaluate how to decrease the number of medication errors in different health care related setting