Search

Aims: We report the results of a real-world study based on heart failure (HF) patients' continuous remote monitoring strategy using the CardioMEMS system to assess the impact of this device on healthcare outcomes, costs, and patients' management and quality of life., Methods and Results: We enrolled seven patients (69.00 ± 4.88 years; 71.43% men) with HF, implanted with CardioMEMS, and daily remote monitored to optimize both tailored adjustments of home therapy and/or hospital infusions of levosimendan. We recorded clinical, pharmacological, biochemical, and echocardiographic parameters and data on hospitalizations, emergency room access, visits, and costs. Following the implantation of CardioMEMS, we observed a 50% reduction in the total number of hospitalizations and a 68.7% reduction in the number of days in the hospital. Accordingly, improved patient quality of life was recorded with EQ-5D (pre 58.57 ± 10.29 vs. 1 year post 84.29 ± 19.02, P = 0.008). Echocardiographic data show a statistically significant improvement in both systolic pulmonary artery pressure (47.86 ± 8.67 vs. 35.14 ± 9.34, P = 0.022) and E/e' (19.33 ± 5.04 vs. 12.58 ± 3.53, P = 0.023). The Quantikine® HS High-Sensitivity Kit determined elevated interleukin-6 values at enrolment in all patients, with a statistically significant reduction after 6 months (P = 0.0211). From an economic point of view, the net savings, including the cost of CardioMEMS, were on average €1580 per patient during the entire period of observation, while the analysis performed 12 months after the implant vs. 12 months before showed a net saving of €860 per patient. The ad hoc analysis performed on the levosimendan infusions resulted in 315 days of hospital avoidance and a saving of €205 158 for the seven patients enrolled during the observation period., Conclusions: This innovative strategy prevents unplanned access to the hospital and contributes to the efficient use of healthcare facilities, human resources, and costs., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cardiovascular diseases (CVDs) are associated with very high rates of re-hospitalization and mortality worldwide, so the complexity of these pathologies requires frequent access to hospital facilities. The guidelines also emphasize the importance of cardiac rehabilitation (CR) programs, which have demonstrated a favorable effect on outcomes, and cardiac telerehabilitation (CTR) could represent an innovative healthcare delivery model. The aim of our review is to study how technologies used in rehabilitation have changed over time and also to understand what types of rehabilitation programs have been used in telerehabilitation., Methods: We searched randomized controlled trials (RCTs) in three electronic databases, PubMed, Web of Science, and Scopus, from January 2015 to January 2024, using relevant keywords. Initially, 502 articles were found, and 79 duplicates were identified and eliminated with EndNote., Results: In total, 16 RCTs fulfilled the pre-defined criteria, which were analyzed in our systematic review. The results showed that after CTR, there was a significant improvement in main outcome measures, as well as in relation to technological advances., Conclusions: Moreover, compared to center-based rehabilitation, CTR can offer further advantages, with better cost-effectiveness, the breakdown of geographical barriers, and the improvement of access to treatment for the female population, which is traditionally more socially committed.

Chronic kidney disease (CKD) is a global health issue with a rising prevalence, affecting 697.5 million people worldwide. It imposes a substantial burden, contributing to 35.8 million disability-adjusted life years (DALYs) and 1.2 million deaths in 2017. The mortality rate for CKD has increased by 41.5% between 1990 and 2017, positioning it as a significant cause of global mortality. CKD is associated with diverse health complications, impacting cardiovascular, neurological, nutritional, and endocrine aspects. One prominent complication is CKD-mineral and bone disorder (MBD), a complex condition involving dysregulation of bone turnover, mineralization, and strength, accompanied by soft tissue and vascular calcification. Alterations in mineral metabolism, including calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and Klotho, play pivotal roles in CKD-MBD. These disturbances, observed early in CKD, contribute to the progression of bone disorders and renal osteodystrophy (ROD). Vascular calcification (VC) is a key component of CKD-MBD, accelerated by CKD. The pathophysiology involves complex processes in vascular smooth muscle cells and the formation of calciprotein particles (CPP). VC is closely linked to cardiovascular events and mortality, emphasizing its prognostic significance. Various serum markers and imaging techniques, including lateral plain X-ray, Kauppila Score, Adragao Score, and pulse wave velocity, aid in VC detection. Additionally, pQCT provides valuable information on arterial calcifications, offering an advantage over traditional scoring systems. CKD poses a substantial global health burden, and its complications, including CKD-MBD and VC, significantly contribute to morbidity and mortality. Understanding the intricate relationships between mineral metabolism, bone disorders, and vascular calcification is crucial for effective diagnosis and therapeutic interventions.

High glucose-induced endothelial dysfunction is an important pathological feature of diabetic vasculopathy. While genome-wide studies have identified an association between type 2 diabetes mellitus (T2DM) and increased expression of a C2 calcium-dependent domain containing 4B (C2CD4B), no study has yet explored the possible direct effect of C2CD4B on vascular function. Vascular reactivity studies were conducted using a pressure myograph, and nitric oxide and oxidative stress were assessed through difluorofluorescein diacetate and dihydroethidium, respectively. We demonstrate that high glucose upregulated both mRNA and protein expression of C2CD4B in mice mesenteric arteries in a time-dependent manner. Notably, the inhibition of C2CD4B expression by genetic knockdown efficiently prevented hyperglycemia-induced oxidative stress, endothelial dysfunction, and loss of nitric oxide (NO) bioavailability. Recombinant C2CD4B evoked endothelial dysfunction of mice mesenteric arteries, an effect associated with increased reactive oxygen species (ROS) and decreased NO production. In isolated human umbilical vein endothelial cells (HUVECs), C2CD4B increased phosphorylation of endothelial nitric oxide synthase (eNOS) at the inhibitory site Thr495 and reduced eNOS dimerization. Pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and PKCα effectively attenuated oxidative stress, NO reduction, impairment of endothelial function, and eNOS uncoupling induced by C2CD4B. These data demonstrate, for the first time, that C2CD4B exerts a direct effect on vascular endothelium via a phosphoinositide 3-kinase (PI3K)/Akt/PKCα-signaling pathway, providing a new perspective on C2CD4B as a promising therapeutic target for the prevention of oxidative stress in diabetes-induced endothelial dysfunction.

Obesity is a growing public health epidemic worldwide and is implicated in slowing improved life expectancy and increasing cardiovascular (CV) risk; indeed, several obesity-related mechanisms drive structural, functional, humoral, and hemodynamic heart alterations. On the other hand, obesity may indirectly cause CV disease, mediated through different obesity-associated comorbidities. Diet and physical activity are key points in preventing CV disease and reducing CV risk; however, these strategies alone are not always sufficient, so other approaches, such as pharmacological treatments and bariatric surgery, must support them. Moreover, these strategies are associated with improved CV risk factors and effectively reduce the incidence of death and CV events such as myocardial infarction and stroke; consequently, an individualized care plan with a multidisciplinary approach is recommended. More precisely, this review explores several interventions (diet, physical activity, pharmacological and surgical treatments) to address CV risk in obese patients and emphasizes the importance of adherence to treatments.

Sacubitril/valsartan (Sac/Val) reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril. However, its effects on functional capacity remain uncertain; consequently, we sought to compare Sac/Val vs. standard medical therapy, in terms of effects on prognostically significant CPET parameters, in HFrEF patients during a long follow-up period. We conducted a single-center, observational study in an HF clinic; specifically, we retrospectively identified that 12 patients switched to Sac/Val and 13 patients that managed with standard, optimal medical therapy (control group). At each visit, baseline, and follow-up (median time: 16 months; IQ range: 11.5-22), we collected demographic information, medical history, vital signs, cardiopulmonary exercise testing, standard laboratory data, pharmacological treatment information, and echocardiographic parameters. The study's primary end-point was the change from baseline in peak VO 2 (adjusted to body weight). We did not observe significant differences between the two study groups at baseline. Similarly, we did not observe any significant differences during the follow-up in mean values of peak VO 2 corrected for body weight: Sac/Val baseline: 12.2 ± 4.6 and FU: 12.7 ± 3.3 vs. control group: 13.1 ± 4.2 and 13.0 ± 4.2 mL/kg/min; p = 0.49. No significant treatment differences were observed for changes in VE/VCO 2 slope: Sac/Val baseline: 35.4 ± 7.4 and FU: 37.2 ± 13.1 vs. control group: 34.6 ± 9.1 and 34.0 ± 7.3; p = 0.49. In conclusion, after a median follow-up period of 16 months, there was no significant benefit of Sac/Val on peak VO 2 and other measures of CPET compared with standard optimal therapy in patients with HFrEF.

Arterial hypertension (AH) is a progressive issue that grows in importance with the increased average age of the world population. The potential role of artificial intelligence (AI) in its prevention and treatment is firmly recognized. Indeed, AI application allows personalized medicine and tailored treatment for each patient. Specifically, this article reviews the benefits of AI in AH management, pointing out diagnostic and therapeutic improvements without ignoring the limitations of this innovative scientific approach. Consequently, we conducted a detailed search on AI applications in AH: the articles (quantitative and qualitative) reviewed in this paper were obtained by searching journal databases such as PubMed and subject-specific professional websites, including Google Scholar. The search terms included artificial intelligence, artificial neural network, deep learning, machine learning, big data, arterial hypertension, blood pressure, blood pressure measurement, cardiovascular disease, and personalized medicine. Specifically, AI-based systems could help continuously monitor BP using wearable technologies; in particular, BP can be estimated from a photoplethysmograph (PPG) signal obtained from a smartphone or a smartwatch using DL. Furthermore, thanks to ML algorithms, it is possible to identify new hypertension genes for the early diagnosis of AH and the prevention of complications. Moreover, integrating AI with omics-based technologies will lead to the definition of the trajectory of the hypertensive patient and the use of the most appropriate drug. However, AI is not free from technical issues and biases, such as over/underfitting, the "black-box" nature of many ML algorithms, and patient data privacy. In conclusion, AI-based systems will change clinical practice for AH by identifying patient trajectories for new, personalized care plans and predicting patients' risks and necessary therapy adjustments due to changes in disease progression and/or therapy response.

Cardiovascular diseases (CVDs) are the leading cause of death and illness in Europe and worldwide, responsible for a staggering 47% of deaths in Europe. Over the past few years, there has been increasing evidence pointing to bioactive sphingolipids as drivers of CVDs. Among them, most studies place emphasis on the cardiovascular effect of ceramides and sphingosine-1-phosphate (S1P), reporting correlation between their aberrant expression and CVD risk factors. In experimental in vivo models, pharmacological inhibition of de novo ceramide synthesis averts the development of diabetes, atherosclerosis, hypertension and heart failure. In humans, levels of circulating sphingolipids have been suggested as prognostic indicators for a broad spectrum of diseases. This article provides a comprehensive review of sphingolipids' contribution to cardiovascular, cerebrovascular and metabolic diseases, focusing on the latest experimental and clinical findings. Cumulatively, these studies indicate that monitoring sphingolipid level alterations could allow for better assessment of cardiovascular disease progression and/or severity, and also suggest them as a potential target for future therapeutic intervention. Some approaches may include the down-regulation of specific sphingolipid species levels in the circulation, by inhibiting critical enzymes that catalyze ceramide metabolism, such as ceramidases, sphingomyelinases and sphingosine kinases. Therefore, manipulation of the sphingolipid pathway may be a promising strategy for the treatment of cardio- and cerebrovascular diseases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to be a global challenge due to resulting morbidity and mortality. Cardiovascular (CV) involvement is a crucial complication in coronavirus disease 2019 (COVID-19), and no strategies are available to prevent or specifically address CV events in COVID-19 patients. The identification of molecular partners contributing to CV manifestations in COVID-19 patients is crucial for providing early biomarkers, prognostic predictors, and new therapeutic targets. The current report will focus on the role of microRNAs (miRNAs) in CV complications associated with COVID-19. Indeed, miRNAs have been proposed as valuable biomarkers and predictors of both cardiac and vascular damage occurring in SARS-CoV-2 infection. SIGNIFICANCE STATEMENT: It is essential to identify the molecular mediators of coronavirus disease 2019 (COVID-19) cardiovascular (CV) complications. This report focused on the role of microRNAs in CV complications associated with COVID-19, discussing their potential use as biomarkers, prognostic predictors, and therapeutic targets., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

COVID-19 infection evokes various systemic alterations that push patients not only towards severe acute respiratory syndrome but causes an important metabolic dysregulation with following multi-organ alteration and potentially poor outcome. To discover novel potential biomarkers able to predict disease's severity and patient's outcome, in this study we applied untargeted lipidomics, by a reversed phase ultra-high performance liquid chromatography-trapped ion mobility mass spectrometry platform (RP-UHPLC-TIMS-MS), on blood samples collected at hospital admission in an Italian cohort of COVID-19 patients (45 mild, 54 severe, 21 controls). In a subset of patients, we also collected a second blood sample in correspondence of clinical phenotype modification (longitudinal population). Plasma lipid profiles revealed several lipids significantly modified in COVID-19 patients with respect to controls and able to discern between mild and severe clinical phenotype. Severe patients were characterized by a progressive decrease in the levels of LPCs, LPC-Os, PC-Os, and, on the contrary, an increase in overall TGs, PEs, and Ceramides. A machine learning model was built by using both the entire dataset and with a restricted lipid panel dataset, delivering comparable results in predicting severity (AUC= 0.777, CI: 0.639-0.904) and outcome (AUC= 0.789, CI: 0.658-0.910). Finally, re-building the model with 25 longitudinal (t1) samples, this resulted in 21 patients correctly classified. In conclusion, this study highlights specific lipid profiles that could be used monitor the possible trajectory of COVID-19 patients at hospital admission, which could be used in targeted approaches., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Wellens' pattern is an electrocardiogram (EKG) finding of biphasic or deeply inverted T waves in leads V2 and V3 that is suggestive of anterior wall ischemia classically reflecting critical stenosis of the proximal left anterior descending artery (LAD). This pattern reflects a preinfarction state that can eventually progress to massive and fatal anterior wall myocardial infarction (MI). We describe a case of a 50-year-old male who presented with chest pain and hypertensive emergency. EKG revealed new biphasic T-waves in V2-V5. The patient's chest pain resolved with blood pressure control, however, the persistence of Wellens' pattern on EKG prompted further investigation. Emergent left heart catheterization (LHC) revealed severe multivessel coronary artery disease, most notably with critical stenosis of the mid-LAD. The patient underwent successful surgical revascularization. This case highlights a classic EKG pattern that can have serious morbidity and mortality if it is missed. This case also describes a unique anatomical correlation of Wellens' syndrome as the coronary lesion was identified in the mid-LAD, contrary to lesions typically identified in the proximal LAD. Prior knowledge about Wellens' pattern allowed us to consider the possibility of critical LAD stenosis, which allowed for timely intervention and prevention of a massive myocardial infarction and possibly death., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Mathew et al.)

Omega-3 fatty acids have been shown to exert several beneficial effects in the prevention of cardiovascular and cerebrovascular diseases. The objective of the present study was to analyze the effects of a novel high-load omega-3 lysine complex, AvailOm ® , its related constituents and a novel mixture of AvailOm ® with specific vasoactive anthocyanins on vascular function in mice resistance artery. Pressure myograph was used to perform vascular reactivity studies. Nitric oxide and oxidative stress were assessed by difluorofluorescein diacetate and dihydroethidium, respectively. Increasing doses of AvailOm ® exerted a dose-response vasorelaxation via AMPK-eNOS-mediated signaling. Omega-3 Ethyl Ester was identified as the main bioactive derivative of AvailOm ® , being capable of inducing vasorelaxant action to the same extent of entire product. The combination of AvailOm ® with a mix of potent vasoactive anthocyanins (C3-glu + DP3-glu + Mal3-glu + Mal3-gal + PEO3-gal), strongly protected mesenteric arteries from vascular dysfunction and oxidative stress evoked by oxidized-LDL. These data demonstrate for the first time the direct effects of AvailOm ® on resistance arteries. The evidence that the combination of specific vasoactive anthocyanins and AvailOm ® further enhanced the vasculoprotective properties of these compounds, may offer new promising perspectives for preventing the onset of cardiovascular and cerebrovascular events.

Conversion of free-standing graphene into pure graphane─where each C atom is sp 3 bound to a hydrogen atom─has not been achieved so far, in spite of numerous experimental attempts. Here, we obtain an unprecedented level of hydrogenation (≈90% of sp 3 bonds) by exposing fully free-standing nanoporous samples─constituted by a single to a few veils of smoothly rippled graphene─to atomic hydrogen in ultrahigh vacuum. Such a controlled hydrogenation of high-quality and high-specific-area samples converts the original conductive graphene into a wide gap semiconductor, with the valence band maximum (VBM) ∼ 3.5 eV below the Fermi level, as monitored by photoemission spectromicroscopy and confirmed by theoretical predictions. In fact, the calculated band structure unequivocally identifies the achievement of a stable, double-sided fully hydrogenated configuration, with gap opening and no trace of π states, in excellent agreement with the experimental results.

Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis in prisoners are higher than the general population and are two public health concerns, especially in low- and middle-income countries. We conducted a cross-sectional study to determine the prevalence and the factors associated with LTBI among the inmate population detained in three Southern Italian penitentiaries. Tuberculin intradermal reaction skin test was performed on the inmates who agreed to participate in the study. In case of positivity, the QuantiFERON-TB test was performed. In those positive to QuantiFERON, chest X-ray films were performed, and treatment initiated. A total of 381 inmates accepted to participate. The prevalence of LTBI was 4.2%. In the analysis, LTBI was associated with no self-reported contact with active tuberculosis patients within the prisons, and 10% of subjects admitted the use of inhaled drugs. No HIV coinfections were found. No cases of active symptomatic tuberculosis were identified during the study period. Our results confirm that incarceration increases the risk of tuberculous infection. Non-EU nationality and a history of drug addiction appear to be major risk factors for tuberculosis infection in the penitentiary setting. Reinforcing tuberculosis control is essential to prevent its transmission in prisons.

A 93-year-old female presented with persistent shortness of breath and wheezing since the consumption of a meal. Her past medical history is significant for a clinical diagnosis of asthma at the age of 88 years, without pulmonary function testing, complicated by several prior visits to the emergency department (ED) for recurrent exacerbations. Multiple bronchodilators in the ED provided only minimal improvement in her symptoms. Chest imaging eventually revealed a giant, fluid-filled hiatal hernia exhibiting a compressive effect on the posterior aspect of the left atrium. The etiology of the patient's airway bronchoconstriction was likely multifactorial. We hypothesize that the extrinsic, dynamic compression of the bronchial tree by the peristaltic motion of the hiatal hernia, microaspiration from gastroesophageal reflux, and peribronchial edema from left atrial compression accounted for our patient's unique presentation. An outpatient methacholine challenge test eventually excluded bronchial asthma. Although she was considered a poor surgical candidate, she has had no further recurrences of her symptoms with counseling on conservative lifestyle changes. This case serves to highlight the heterogeneity in presentations of hiatal hernias, particularly in elderly females. Furthermore, it remains prudent to maintain a broad differential for wheezing, as evidenced by our patient who was previously managed for a number of years as poorly controlled asthma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Karan et al.)

Though the acute effects of SARS-CoV-2 infection have been extensively reported, the long-term effects are less well described. Specifically, while clinicians endure to battle COVID-19, we also need to develop broad strategies to manage post-COVID-19 symptoms and encourage those affected to seek suitable care. This review addresses the possible involvement of the lung, heart and brain in post-viral syndromes and describes suggested management of post-COVID-19 syndrome. Post-COVID-19 respiratory manifestations comprise coughing and shortness of breath. Furthermore, arrhythmias, palpitations, hypotension, increased heart rate, venous thromboembolic diseases, myocarditis and acute heart failure are usual cardiovascular events. Among neurological manifestations, headache, peripheral neuropathy symptoms, memory issues, lack of concentration and sleep disorders are most commonly observed with varying frequencies. Finally, mental health issues affecting mental abilities and mood fluctuations, namely anxiety and depression, are frequently seen. Finally, long COVID is a complex syndrome with protracted heterogeneous symptoms, and patients who experience post-COVID-19 sequelae require personalized treatment as well as ongoing support.

The recovery of high added value compound from waste stream is fundamental to keep biotechnological processes sustainable. In this study, anaerobic digestion of two highly produced organic waste was integrated with microalgae-based processes both to treat liquid digestate and recover high value compounds. Chlorella vulgaris growth was assessed for lipids accumulation and subsequent recovery, using two types of digestate: organic waste and sewage sludge digestate (DIG-OFMSW) and wine lees digestate (DIG-WL). Growth tests were carried out in batch mode and results showed a slightly higher final biomass concentration from DIG-WL (1.36 ± 0.09 g l -1 ) compared to DIG-OFMSW (1.05 ± 0.13 g l -1 ) and a clearly different lipids accumulation yield (28.86 ± 0.05% in DIG-WL compared to 6.1 ± 0.2% of DIG-OFMSW, on total solids). Lipid characterization showed a high oleic acid accumulation (69.52 ± 0.50%w/w in DIG-WL) that positively influence biodiesel properties and a low linolenic acids content (below 0.30%w/w) that comply with European law EN14214 for biodiesel (linolenic acid content lower than 12%w/w). In addition, due to the high concentration of palmitic and stearic acids detected at the end of test, this oil can be used as new substrate to produce stearin, normally produced from palm oil., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Constipation is a condition that is very prevalent and is reported in up to 40 percent of individuals with intellectual and developmental disabilities (IDD). Constipation in this patient population is most commonly secondary to neuromuscular abnormalities, immobility, suboptimal diet, and medication side effects. History taking is frequently limited in adults with IDD due to communication barriers, often leading to a missed diagnosis of constipation. Inadequately treated constipation may lead to adverse effects including behavioral disturbances, fecal impaction, intestinal obstruction, and even death from intestinal perforation and sepsis. As a result, a high index of suspicion must exist for this patient population. Treatment in these patients requires an individualized approach, to reduce the constipation and its associated health complications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Reshmi Mathew et al.)

Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge.

Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which are still under study. Cardiovascular sequelae of COVID-19 include heart failure, cardiomyopathy, acute coronary syndrome, arrhythmias, and venous thromboembolism. This article aims to collect scientific evidence by exploiting PubMed, Scopus, and Pedro databases to highlight the cardiovascular complications of COVID-19 and to define the physiotherapy treatment recommended for these patients. Exercise training (ET), an important part of cardiac rehabilitation, is a powerful tool in physiotherapy, capable of inducing significant changes in the cardiovascular system and functional in the recovery of endothelial dysfunction and for the containment of thromboembolic complications. In conclusion, due to the wide variety of possible exercise programs that can be obtained by combining intensity, duration, and speed in various ways, and by adjusting the program based on continuous patient monitoring, exercise training is well suited to the treatment of post-COVID patients with an impaired cardiovascular system of various degrees.

Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection.

Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.

A suitable way to modify the electronic properties of graphene-while maintaining the exceptional properties associated with its two-dimensional (2D) nature-is its functionalisation. In particular, the incorporation of hydrogen isotopes in graphene is expected to modify its electronic properties leading to an energy gap opening, thereby rendering graphene promising for a widespread of applications. Hence, deuterium (D) adsorption on free-standing graphene was obtained by high-energy electron ionisation of D2 and ion irradiation of a nanoporous graphene (NPG) sample. This method allows one to reach nearly 50 at.% D upload in graphene, higher than that obtained by other deposition methods so far, towards low-defect and free-standing D-graphane. That evidence was deduced by X-ray photoelectron spectroscopy of the C 1s core level, showing clear evidence of the D-C sp3 bond, and Raman spectroscopy, pointing to remarkably clean and low-defect production of graphane. Moreover, ultraviolet photoelectron spectroscopy showed the opening of an energy gap in the valence band. Therefore, high-energy electron ionisation and ion irradiation is an outstanding method for obtaining low defect D-NPG with a high D upload, which is very promising for the fabrication of semiconducting graphane on large scale.

A 49-year-old male with a history of nonischemic heart failure with reduced ejection fraction, hypertension, diabetes was admitted for cardiogenic shock. Treatment started with a high dose of dobutamine infusion. While the patient's volume status improved, his clinical status declined as he became febrile and hypotensive. He was found to have severe dobutamine-induced eosinophilia, corrected only upon dobutamine cessation and steroid administration. A comprehensive investigation ruled out other potential etiologies. Peripheral eosinophilia is a rare adverse effect associated with dobutamine, leading to a significant deterioration in already decompensated patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Maaliki et al.)

Introduction: HCV infection elimination is set to be carried out by 2030. To achieve this goal, the WHO has set minor achievable short-term "mini-goals." One of these is treating "difficult to reach and treat populations," such as prisoners. One of the biggest obstacles to achieving this mini goal is the poor knowledge of the real HCV prevalence in such a population and the barriers to its detection, treatment, and follow-up. Even if HCV testing in Italian prisons is feasible and recommended, it is not however always carried out. To worsen the picture, the peculiar status of conviction is correlated to difficulty in caring out the antiviral therapy due to loss in follow-up and to the refusals by inmates., Aims: A point-of-care test-and-treat program was set up in a penitentiary in Southern Italy to reduce the number of patients Lost To Follow-Up (LTFU) between detection and treatment. A secondary aim was to evaluate the prevalence of HCV-infected patients in a cohort of newly arrived inmates., Methods: This prospective-observational study was carried out from January 2020 to February 2020. We performed an HCV-RNA blood capillary quick test on all newly arrived inmates. As a routine, the new inmates underwent clinical and laboratory assessments. To those who were detected HCV-RNA positive, the shortest possible antiviral treatment was offered, according to genotype and clinical features., Results: We observed 122 new inmates in the period between January and February of 2020. Overall, 62 (50.8%) subjects took HCV-RNA quick testing through blood sampling. Four (6.4%) subjects were found to be HCV-RNA positive; 1 refused antiviral therapy, while 3 accepted, obtaining 100% SVR. None of the HCV-active inmates were lost to follow up between detection and treatment proposal., Conclusion: The use of a high-speed test-and-treat protocol for HCV infection was demonstrated to be effective in avoiding LTFU in HCV-positive new inmates in the period between detection and treatment. We observed an apparent prevalence of HCV incident cases in newly arrived inmates of 6.4%. Antiviral therapy was quickly provided and found to be effective and successful., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cardiovascular diseases (CVDs) such as hypertension, atherosclerosis, myocardial infarction, and diabetes are a significant public health problem worldwide. Although several novel pharmacological treatments to reduce the progression of CVDs have been discovered during the last 20 years, the better way to contain the onset of CVDs remains prevention. In this regard, nutraceuticals seem to own a great potential in maintaining human health, exerting important protective cardiovascular effects. In the last years, there has been increased focus on identifying natural compounds with cardiovascular health-promoting effects and also to characterize the molecular mechanisms involved. Although many review articles have focused on the individual natural compound impact on cardiovascular diseases, the aim of this manuscript was to examine the role of the most studied nutraceuticals, such as resveratrol, cocoa, quercetin, curcumin, brassica, berberine and Spirulina platensis, on different CVDs.

(1) Background: The emergency linked to the spread of COVID-19 in Italy has led to inevitable consequences on the penitentiary system. The risks of this emergency in prisons is mainly related to the problem of persistent overcrowding that makes social distancing difficult and the isolation of any contagion hard to arrange. The Department of Protection for Adults and Minors of the ASL Salerno Criminal Area has taken steps in order to perform screening operations and minimize the risks for prisoners and operators. (2) Methods: We conducted a two-phase observational study. In the first phase, we offered and then executed serum COVID-19 screening to all the convicted inmates. For those who had a doubtful or positive result, a swab was executed in the shortest time possible. In the second phase, a pharyngeal swab was offered and executed to all the police officers, the penitentiary administrative staff and the medical personnel working in the prison. (3) Results: In the first phase, we executed 485 COVID-19 blood tests on prisoners, 3 (0.61%) of which were positive. The three positive inmates underwent nasopharyngeal swabbing, which ultimately were negative. After that, we executed 276 nasopharyngeal swabs on the prison personnel, penitentiary administrative staff and medical personnel-all were negative. (4) Conclusion: All tests (blood tests and swabs) that were carried out on the prisoners and on the staff were negative for COVID-19. We believe that all prisons in Italy and in the world should take action to ensure preventive and control measures in order to safeguard the health of the prison population and of all the people who work there.

Background: An unmet objective in the pursuit of HCV elimination is the creation of a simple and fast operating model to identify difficult-to-treat populations, like prisoners. Of many obstacles, the first is represented by the poor knowledge of inmates HCV-Ab prevalence. Moreover, due to the peculiar status of conviction, often their access to antiviral therapy is neglected., Aims: To evaluate the prevalence of HCV infection in a penitentiary Institution of Southern Italy through a point-of-care screening and treatment program., Methods: We conducted a prospective observational study in two phases: first, we reviewed all the prisoners' clinical records, to verify HCV-Ab execution. Subsequently, we performed a universal point-of-care screening and treatment program., Results: We enrolled 670 patients. Overall, 310(46.27%) were already HCV-Ab tested. At the screening initiation, 23.28% patients were discharged, whereas 8.35% refused. Of the remaining 458 subjects, 58(12.67%) were HCV-Ab positive and 46 HCVRNA positive. All these underwent DAA, obtaining 100% SVR. At the end of the program, a total of 491(73.28%) subjects had HCV-Ab available. Sixty-nine (14.05%) were positive. A total of 214(31.94%) subjects were lost to follow-up., Conclusions: We revealed a prevalence of 14.05% of HCV-Ab in conviction. Antiviral treatment was safe and efficacious. More efforts are advisable to provide screening for HCV-Ab in conviction., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background High blood pressure (BP) has long been recognized as a major health threat and, particularly, a major risk factor for stroke, cardiovascular disease, and end-organ damage. However, the identification of a novel, alternative, integrative approach for the control of BP and cardiovascular protection is still needed. Methods and Results Sixty-nine uncontrolled hypertension patients, aged 40 to 68 years, on antihypertensive medication were enrolled in 2 double-blind studies. Forty-five were randomized to placebo or a new nutraceutical combination named AkP05, and BP, endothelial function, and circulating nitric oxide were assessed before and at the end of 4 weeks of treatment. Twenty-four patients were randomized to diuretic or AkP05 for 4 weeks and underwent a cardiopulmonary exercise test to evaluate the effects of AkP05 on functional capacity of the cardiovascular, pulmonary, and muscular systems. Vascular and molecular studies were undertaken on mice to characterize the action of the single compounds contained in the AkP05 nutraceutical combination. AkP05 supplementation reduced BP, improved endothelial function, and increased nitric oxide release; cardiopulmonary exercise test revealed that AkP05 increased maximum O 2 uptake, stress tolerance, and maximal power output. In mice, AkP05 reduced BP and improved endothelial function, evoking increased nitric oxide release through the PKCα/Akt/endothelial nitric oxide synthase pathway and reducing reactive oxygen species production via NADPH-oxidase inhibition. These effects were mediated by synergism of the single compounds of AkP05. Conclusions This is the first study reporting positive effects of a nutraceutical combination on the vasculature and exercise tolerance in treated hypertensive patients. Our findings suggest that AkP05 may be used as an adjunct for the improvement of cardiovascular protection and to better control BP in uncontrolled hypertension.

A 61-year-old Caucasian woman presented to the emergency room complaining of left-sided chest pain and altered mentation for 3 days. Her medical history included liver cirrhosis and coronary artery disease. On admission, she was found to have methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Due to a decline in mental status, a lumbar puncture was performed and cerebrospinal fluid cultures grew MRSA. She was treated initially with vancomycin. Ceftaroline was later added, due to the high burden of disease and difficulty in clearing her infection. After initiation of ceftaroline, bacteraemia cleared and mental status improved, however, she developed haemolytic anaemia. Ceftaroline was stopped and vancomycin continued. Staphylococcal meningitis is a rare occurrence, estimated at a rate of only 1%-10% of all bacterial meningitis cases. Ceftaroline seems to be a suitable option for disseminated MRSA infection, including MRSA meningitis, when the clinical response to vancomycin is inadequate. Further studies are warranted in order to establish adequate dosing while avoiding adverse effects., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Diabetes mellitus is a common disease that affects 3⁻5% of the general population in Italy. In some countries of northern Europe or in North America, it can even affect 6⁻8% of the population. Of great concern is that the number of cases of diabetes is constantly increasing, probably due to the increase in obesity and the sedentary nature of the population. According to the World Health Organization, in the year 2030 there will be 360 million people with diabetes, compared to 170 million in 2000. This has important repercussions on the lives of patients and their families, and on health systems that offer assistance to patients. In this review, we try to describe in an organized way the pathophysiological continuity between diabetes mellitus, endothelial dysfunction, and platelet hyperaggregation, highlighting the main molecular mechanisms involved and the interconnections.

A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.

We report the mass measurement of ^{56}Cu, using the LEBIT 9.4 T Penning trap mass spectrometer at the National Superconducting Cyclotron Laboratory at Michigan State University. The mass of ^{56}Cu is critical for constraining the reaction rates of the ^{55}Ni(p,γ) ^{56}Cu(p,γ) ^{57}Zn(β^{+}) ^{57}Cu bypass around the ^{56}Ni waiting point. Previous recommended mass excess values have disagreed by several hundred keV. Our new value, ME=-38626.7(7.1)  keV, is a factor of 30 more precise than the extrapolated value suggested in the 2012 atomic mass evaluation [Chin. Phys. C 36, 1603 (2012)CPCHCQ1674-113710.1088/1674-1137/36/12/003], and more than a factor of 12 more precise than values calculated using local mass extrapolations, while agreeing with the newest 2016 atomic mass evaluation value [Chin. Phys. C 41, 030003 (2017)CPCHCQ1674-113710.1088/1674-1137/41/3/030003]. The new experimental average, using our new mass and the value from AME2016, is used to calculate the astrophysical ^{55}Ni(p,γ) and ^{56}Cu(p,γ) forward and reverse rates and perform reaction network calculations of the rp process. These show that the rp-process flow redirects around the ^{56}Ni waiting point through the ^{55}Ni(p,γ) route, allowing it to proceed to higher masses more quickly and resulting in a reduction in ashes around this waiting point and an enhancement to higher-mass ashes.

We report the determination of the Q(EC) value of the mirror transition of (11)C by measuring the atomic masses of (11)C and (11)B using Penning trap mass spectrometry. More than an order of magnitude improvement in precision is achieved as compared to the 2012 Atomic Mass Evaluation (Ame2012) [Chin. Phys. C 36, 1603 (2012)]. This leads to a factor of 3 improvement in the calculated Ft value. Using the new value, Q(EC)=1981.690(61)  keV, the uncertainty on Ft is no longer dominated by the uncertainty on the Q(EC) value. Based on this measurement, we provide an updated estimate of the Gamow-Teller to Fermi mixing ratio and standard model values of the correlation coefficients.

Long-term ecological datasets are vital for investigating how species respond to changes in their environment, yet there is a critical lack of such datasets from aquatic systems. We developed otolith growth 'chronologies' to reconstruct the growth history of a temperate estuarine fish species, black bream (Acanthopagrus butcheri). Chronologies represented two regions in south-east Australia: South Australia, characterised by a relatively warm, dry climate, and Tasmania, characterised by a relatively cool, wet climate. Using a mixed modelling approach, we related inter-annual growth variation to air temperature, rainfall, freshwater inflow (South Australia only), and El Niño-Southern Oscillation events. Otolith chronologies provided a continuous record of growth over a 13- and 21-year period for fish from South Australia and Tasmania, respectively. Even though fish from Tasmania were sourced across multiple estuaries, they showed higher levels of growth synchronicity across years, and greater year-to-year growth variation, than fish from South Australia, which were sourced from a single, large estuary. Growth in Tasmanian fish declined markedly over the time period studied and was negatively correlated to temperature. In contrast, growth in South Australian fish was positively correlated to both temperature and rainfall. The stark contrast between the two regions suggests that Tasmanian black bream populations are more responsive to regional scale environmental variation and may be more vulnerable to global warming. This study highlights the importance of examining species response to climate change at the intra-specific level and further validates the emerging use of growth chronologies for generating long-term ecological data in aquatic systems.

We report the first direct measurement of the (14)O superallowed Fermi β-decay QEC value, the last of the so-called "traditional nine" superallowed Fermi β decays to be measured with Penning trap mass spectrometry. (14)O, along with the other low-Z superallowed β emitter, (10)C, is crucial for setting limits on the existence of possible scalar currents. The new ground state QEC value, 5144.364(25) keV, when combined with the energy of the 0(+) daughter state, Ex(0(+))=2312.798(11)  keV [F. Ajzenberg-Selove, Nucl. Phys. A523, 1 (1991)], provides a new determination of the superallowed β-decay QEC value, QEC(sa)=2831.566(28)  keV, with an order of magnitude improvement in precision, and a similar improvement to the calculated statistical rate function f. This is used to calculate an improved Ft value of 3073.8(2.8) s.

This study quantified the per cent contribution of water chemistry to otolith chemistry using enriched stable isotopes of strontium ((86) Sr) and barium ((137) Ba). Euryhaline barramundi Lates calcarifer, were reared in marine (salinity 40), estuarine (salinity 20) and freshwater (salinity 0) under different temperature treatments. To calculate the contribution of water to Sr and Ba in otoliths, enriched isotopes in the tank water and otoliths were quantified and fitted to isotope mixing models. Fulton's K and RNA:DNA were also measured to explore the influence of fish condition on sources of element uptake. Water was the predominant source of otolith Sr (between 65 and 99%) and Ba (between 64 and 89%) in all treatments, but contributions varied with temperature (for Ba), or interactively with temperature and salinity (for Sr). Fish condition indices were affected independently by the experimental rearing conditions, as RNA:DNA differed significantly among salinity treatments and Fulton's K was significantly different between temperature treatments. Regression analyses did not detect relations between fish condition and per cent contribution values. General linear models indicated that contributions from water chemistry to otolith chemistry were primarily influenced by temperature and secondly by fish condition, with a relatively minor influence of salinity. These results further the understanding of factors that affect otolith element uptake, highlighting the necessity to consider the influence of environment and fish condition when interpreting otolith element data to reconstruct the environmental histories of fish., (© 2015 The Fisheries Society of the British Isles.)

The Piedmont Group of Clinical Nephrology compared the activity of 15 nephrology centers in Piedmont and Aosta Valley as regards bone protection in patients on corticosteroids therapy. Fracture prevalence shows great variability: in 4/15 centers (27%) no fractures were found, in 6/15 centers (40%) fractures were present in 1-4% of cases, in 1 center in 18% of patients. Clinical risk of fracture was based on sex, age and postmenopausal status in 11/14 of the centers (79%), history of fractures and bone disease in 4/14 centers (27%), smoking and alcohol consumption in 3 and 2 centers respectively, glucocorticoid dose and duration in 4, in children bone age and calcium phosphorus status. Dual energy X-ray absorptiometry was performed in 12 centers based on risk factors, in 8 (57%) DXA was performed during the follow-up, in 4 it was performed after 12 months and in 2 after 2-3 years. DXA is not prescribed in children. Only in one center, risk assessment is based on FRAX. Most of the patients are treated with vitamin D supplementation at a dose of steroids of 5 mg/d (80%). Calcium carbonate is used in 9 centers (60%), in two it is used only in the presence of low ionized calcium or bone mineral density. Bisphosphonates are used following AIFA prescription, in particular alendronate in all centers, risedronate in seven and denosumab in one. The analysis shows the great variability of the clinical and therapeutic approach regarding bone protection in patients on corticosteroids therapy, in Piedmont and Aosta Valley.

Background: Often the reduced contrast enhancement on CT renal imaging is radiologically interpreted as acute pyelonephritis (PNA), but it is the task of the clinician to assess a possible differential diagnosis such as a renal infarct and look for a cause., Methods: In our experience (2010-2013), we hospitalized 51 patients with radiological imaging consistent with acute pyelonephritis in native kidneys. However, three of these cases result, after a second look, to be ischemic lesions, only sometimes complicated by over-infections (Tabella 1)., First Case: a woman hospitalized for fever and flank pain with blood culture positive for Klebsiella Pneumoniae. Antibiotic therapy allowed a clinical-laboratory improvement, but after 45 days persisted a focal wedge to the CT scan. The labs showed a anemia due to a sickle cell disease (SLC). The overview was finally interpreted as a renal infarct secondary to a sickle cell anemia, initially complicated by over-infection., Second Case: a men hospitalized for a acute flank pain. The CT scan showed a left renal infarct and a partial renal artery thrombosis, resulting in abuse of cannabinoids and LAC positivity.Third case: a woman hospitalized for flank pain and slight movement of inflammatory markers. CT showed a cuneiform area in the right kidney not vascularized, that did not resolved after prolonged antibiotic therapy. The labs evidence a heterozygous mutation of prothrombin and MTHFR causing the renal infarction., Conclusions: 6% of radiographic imaging consistent with acute pyelonephritis concealed an underlying infarct, due to a unknown state of thrombophilia. The presence of hypovascular imaging to the TC scan, therefore, requires a differential diagnosis between PNA and infarct, especially in the case of atypical development.

Partial migration occurs in many taxa and ecosystems and may confer survival benefits. Here, we use otolith chemistry data to determine whether fish from a large estuarine system were resident or migratory, and then examine whether contingents display differences in modelled growth based on changes in width of otolith growth increments. Sixty-three per cent of fish were resident based on Ba : Ca of otoliths, with the remainder categorized as migratory, with both contingents distributed across most age/size classes and both sexes, suggesting population-level bet hedging. Migrant fish were in slightly better condition than resident fish based on Fulton's K condition index. Migration type (resident versus migratory) was 56 times more likely to explain variation in growth than a model just incorporating year- and age-related growth trends. While average growth only varied slightly between resident and migratory fish, year-to-year variation was significant. Such dynamism in growth rates likely drives persistence of both life-history types. The complex relationships in growth between contingents suggest that management of species exhibiting partial migration is challenging, especially in a world subject to a changing climate., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

Background: A relationship between echolucency of carotid plaques and the consequent risk of ipsilateral ischemic stroke has been observed. An aggressive lipid-lowering therapy may increase the echogenicity of carotid plaque in patients with elevated low-density lipoprotein cholesterol levels. The aim of this study is to prospectively evaluate the long-term effect of high-dose atorvastatin on carotid plaque morphology in patients with first-ever transient ischemic attack or stroke., Methods: All patients with symptomatic first ischemic atherosclerotic cerebrovascular event occurred within the previous 10 days were enrolled. Carotid Doppler ultrasound of the neck vessels with 7-11 MHz probe for the definition of the atherosclerotic carotid framework was performed. The analysis of the gray-scale median (GSM) of each plate was carried out with image processing software., Results: A total of 240 symptomatic plaques were included and divided into 3 groups: 80 in group A (atorvastatin 80 mg), 80 in group B (atorvastatin 40 mg), and 80 to group C (no atorvastatin). GSM score increases significantly more extensive in group A than in group B (+48.65 vs. +39.46, P < .02) and group C (+48.65 vs. 19.3, P = .0002). An inverse association between reduction of low-density lipoprotein and the increase in the GSM score (r = -.456, P = .007) has been observed. Moreover, the reduction of high-sensitive C-reactive protein correlates inversely with the increase of the GSM (r = -.398, P = .021)., Conclusions: Dose-dependent effect of atorvastatin on symptomatic carotid plaque morphology may suggest a specific role of this drug in the atherosclerotic stroke prevention., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Although recent studies excluded an association between Chronic Cerebrospinal Venous Insufficiency and Multiple Sclerosis (MS), controversial results account for some cerebrovascular haemodynamic impairment suggesting a dysfunction of cerebral autoregulation mechanisms. The aim of this cross-sectional, case-control study is to evaluate cerebral arterial inflow and venous outflow by means of a non-invasive ultrasound procedure in Relapsing Remitting (RR), Primary Progressive (PP) Multiple Sclerosis and age and sex-matched controls subjects., Material and Methods: All subjects underwent a complete extra-intracranial arterial and venous ultrasound assessment with a color-coded duplex sonography scanner and a transcranial doppler equipment, in both supine and sitting position by means of a tilting chair. Basal arterial and venous morphology and flow velocities, postural changes in mean flow velocities (MFV) of middle cerebral arteries (MCA), differences between cerebral venous outflow (CVF) in clinostatism and in the seated position (ΔCVF) and non-invasive cerebral perfusion pressure (CPP) were evaluated., Results: 85 RR-MS, 83 PP-MS and 82 healthy controls were included. ΔCVF was negative in 45/85 (52.9%) RR-MS, 63/83 (75.9%) PP-MS (p = 0.01) and 11/82 (13.4%) controls (p<0.001), while MFVs on both MCAs in sitting position were significantly reduced in RR-MS and PP-MS patients than in control, particularly in EDSS ≥ 5 subgroup (respectively, 42/50, 84% vs. 66/131, 50.3%, p<0.01 and 48.3 ± 2 cm/s vs. 54.6 ± 3 cm/s, p = 0.01). No significant differences in CPP were observed within and between groups., Conclusions: The quantitative evaluation of cerebral blood flow (CBF) and CVF and their postural dependency may be related to a dysfunction of autonomic nervous system that seems to characterize more disabled MS patients. It's not clear whether the altered postural control of arterial inflow and venous outflow is a specific MS condition or simply an "epiphenomenon" of neurodegenerative events.

Background: Inactivating mutations of the calcium-sensing receptor (CaSR), of the G-protein subunit α11 (GNA11) and of the adaptor-related protein complex 2, sigma 1 subunit (AP2S1) genes are responsible for familial hypocalciuric hypercalcaemia (FHH). The aim of this study was to analyse prevalence and pathogenicity of CaSR, GNA11 and AP2S1 mutations in patients with an FHH phenotype and to compare them with a sample of patients with primary hyperparathyroidism (PHPT) in order to identify the most useful laboratory parameter for a differential diagnosis., Methods: Patients with an FHH phenotype were studied with polymerase chain reaction amplification and direct sequencing of the entire CaSR, GNA11 and AP2S1 coding sequences. Novel mutations were introduced in a Myc-tagged human wild-type (WT) CaSR cDNA-expressing vector, and functional assay was performed on human embryonic kidney cells evaluating expression and function of mutated proteins., Results: Among 16 FHH patients, none had an inactivating GNA11 or AP2S1 mutation while 3 (18.8%) carried a CaSR mutation and 10 (62.5%) at least one CaSR polymorphism. Within the latter group, 7 of 10 patients had more than one polymorphism (4.1 ± 2.1 per patient). Two novel CaSR mutations [c.2120A>T (E707V) and c.2320G>A (G774S)] were identified: the E707V mutation prevented CaSR expression (western blot), whereas the G774S mutation determined a reduced receptor sensitivity to calcium (IP3 assay). PHPT patients showed significantly (P < 0.001) higher serum calcium, parathyroid hormone, urinary calcium and calcium-creatinine clearance ratio (CCCR) and significantly lower serum phosphate than FHH ones., Conclusions: FHH should be clearly differentiated by PHPT to avoid unnecessary surgery: CCCR could be a useful screening tool while genetic analysis should include the two novel CaSR mutations herein described. The role of multiple polymorphisms deserves further investigation in patients with an FHH phenotype., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Patients with a rare genetic disease may receive renal transplantation (KTx) without a correct diagnosis of causal nephropathy and therefore develop unexpected and even severe complications. The aim of the study was to describe the cases of rare genetic disorders diagnosed after KTx, in order to draw clinical lessons for the transplant physician., Methods: We retrospectively assessed all patients who had received a diagnosis of a rare genetic disorder after KTx., Results: In our center, more than 30% (278/911) of kidney transplant (KTx) recipients were diagnosed with a causal nephropathy: Prevalence of rare genetic disorders in this group was 4.32% (12/278), including 2,8-dihydroxyadeninuria (2,8-DHA) disease (n = 2), HNF-1B-associated nephropathy (n = 2), UMOD-related nephropathy (n = 5), Fabry disease (n = 1), INF2 focal segmental glomerulosclerosis (n = 1), and Senior-Løken syndrome (n = 1). 2,8-DHA nephropathy relapsed in both patients causing an acute renal failure and jeopardizing the graft., Conclusions: Kidney transplant recipients without a diagnosis of causal nephropathy appear to be a selected population in which rare genetic diseases might be more common than expected. As even a belated diagnosis after KTx can have a significant impact on graft and patient survival and on other family members, this possibility should be evaluated in KTx recipients without a known causal nephropathy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)