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The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe. [ABSTRACT FROM AUTHOR]

In the course of the psychiatrist-patient relationship, and especially during a psychotherapy, an image sometimes appears that is greeted by the therapist with a sense of surprise and rediscovery. Such an image has the quality of condensing many of the scattered elements of the patient's life and giving them a form that makes it possible to recognise something stable and permanent in the functioning of the patient's subjectivity. I propose to call these images, which have a valence of enlightenment, clarification and condensation of scattered elements, structuring images. I have used the term 'epiphany' to define these moments of enlightenment, which are of great help in psychiatric and psychotherapeutic work, contributing to a new construction of the history and relationships of the patient's life. [ABSTRACT FROM AUTHOR]

Background: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS). Objective: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects. Methods: Prospective 2-year study including two cohorts of young (18–35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay. Results: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration (p = 0.05), smoking (p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT (p = 0.00007), high-efficacy therapies (p = 0.001), brain lesion volume (BLV) (p = 0.011), and number of T2 lesions (p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm3 and white matter volume 1.78 cm3. Conclusion: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS. [ABSTRACT FROM AUTHOR]

Background: Systemic Sclerosis (SSc), an intricate autoimmune disease causing tissue fibrosis, introduces cardiovascular complexities, notably pulmonary hypertension (PH), affecting both survival and quality of life. This study centers on evaluating echocardiographic parameters and endothelial function using flow‐mediated dilatation (FMD) in SSc patients, aiming to differentiate those with and without pulmonary arterial hypertension (PAH). The emphasis lies in early detection, given the heightened vulnerability of the right ventricle (RV) in the presence of PH. Methods: Fifty‐nine SSc patients and 48 healthy subjects participated, undergoing clinical examinations, echocardiography, FMD assessments, blood analyses, and right heart catheterization (RHC) according to the ESC/ERS guidelines for diagnosis and treatment of PH. Results: SSc‐PAH patients displayed lower FMD, higher frequency of TAPSE < 18 mm, RA area > 18 cm2, act RVOT < 105 ms and TRV > 280 cm/s compared to those without PAH and healthy controls. Resting resistivity index (RI) was higher in SSc patients, with no significant difference between those with and without PAH. Lower FMD% serves as a predictive marker for adverse cardiovascular outcomes in both SSc and SSc‐PAH patients. Stratification by TRV levels and PAH presence reveals notable FMD% variations, emphasizing its potential utility. Conclusions: Early identification of endothelial dysfunction and impaired RV echocardiographic parameters, such as TAPSE and TRV, could aid in predicting right ventricular dysfunction and PAH in SSc patients. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a rare subtype of group 1 pulmonary hypertension (PH) diseases, characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. PAH involves complex mechanisms: vasoconstriction, vascular remodeling, endothelial dysfunction, inflammation, oxidative stress, fibrosis, RV remodeling, cellular hypoxia, metabolic imbalance, and thrombosis. These mechanisms are mediated by several pathways, involving molecules like nitric oxide and prostacyclin. PAH diagnosis requires clinical evaluation and right heart catheterization, confirming a value of mPAP ≥ 20 mmHg at rest and often elevated pulmonary vascular resistance (PVR). Even if an early and accurate diagnosis is crucial, PAH still lacks effective biomarkers to assist in its diagnosis and prognosis. Biomarkers could contribute to arousing clinical suspicion and serve for prognosis prediction, risk stratification, and dynamic monitoring in patients with PAH. The aim of the present review is to report the main novelties on new possible biomarkers for the diagnosis, prognosis, and treatment monitoring of PAH. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension is a complex pathology whose etiology is still not completely well clarified. The pathogenesis of pulmonary arterial hypertension involves different molecular mechanisms, with endothelial dysfunction playing a central role in disease progression. Both individual genetic predispositions and environmental factors seem to contribute to its onset. To further understand the complex relationship between endothelial and pulmonary hypertension and try to contribute to the development of future therapies, we report a comprehensive and updated review on endothelial function in pulmonary arterial hypertension. [ABSTRACT FROM AUTHOR]

Heart failure (HF) represents a significant global health challenge, characterized by high morbidity and mortality rates, and imposes considerable burdens on healthcare systems and patient quality of life. Traditional management strategies, primarily relying on clinical assessments and standard biomarkers like natriuretic peptides, face limitations due to the heterogeneity of HF. This review aims to delve into the evolving landscape of non-natriuretic biomarkers and the transformative potential of omics technologies, underscoring their roles in advancing HF treatment towards precision medicine. By offering novel insights into the biological underpinnings of HF, including inflammation, myocardial stress, fibrosis, and metabolic disturbances, these advancements facilitate more accurate patient phenotyping and individualized treatment strategies. The integration of non-natriuretic biomarkers and omics technologies heralds a pivotal shift in HF management, enabling a move towards tailored therapeutic interventions. This approach promises to enhance clinical outcomes by improving diagnostic accuracy, risk stratification, and monitoring therapeutic responses. However, challenges such as the variability in biomarker levels, cost-effectiveness, and the standardization of biomarker testing across different healthcare settings pose hurdles to their widespread adoption. Despite these challenges, the promise of precision medicine in HF, driven by these innovative biomarkers and technologies, offers a new horizon for improving patient care and outcomes. This review advocates for the further integration of these advancements into clinical practice, highlighting the need for ongoing research to fully realize their potential in transforming the landscape of heart failure management. [ABSTRACT FROM AUTHOR]

Background: SGLT2 inhibitors have been shown to reduce hospitalisation in patients with chronic heart failure (CHF). The cardioprotective mechanisms of gliflozins however have not been fully elucidated. The aim of this study was therefore to evaluate the effect of SGLT2 inhibitors on right and left ventricular function in patients with diabetes and HF. Methods: Seventy‐eight patients with diabetes and CHF were enroled in the study and followed up; 38 started treatment with SGLT2i, while the remaining 40 continued their previous antidiabetic therapy. All patients underwent conventional, TDI and strain echocardiography in an ambulatory setting, at the beginning and after 3 months of therapy with SGLT2i. Results: After 3 months of therapy with SGLT2i, echocardiographic parameters assessing both left and right ventricular dimensions and function were found as significantly improved in patients switching to SGLT2i than control group: LVEF (45 ± 9% vs. 40 ± 8%, p < 0.001), LVEDD (54 ± 6.5 vs. 56 ± 6.5 mm, p < 0.01), GLS (−13 ± 4% vs. −10 ± 3%, p < 0.001), TAPSE (21 ± 3 vs. 19 ± 3 mm, p < 0.001), RV S' (12.9 ± 2.5 vs 11.0 ± 1.9 cm/sec, p < 0.001) and PAsP (24 ± 8 vs. 31 ± 9 mmHg, p < 0.001). Also mitral (1.0 ± 0.5 vs. 1.3 ± 0.5, p < 0.01) and tricuspid regurgitation (1.0 ± 0.5 vs. 1.3 ± 0.5, p < 0.01) improved after SGLT2i therapy. Changes were not statistically significant in patients not treated with SGLT2i (p n.s. in all cases). Conclusions: In a real‐world scenario, treatment with SGLT2i in patients with CHF and diabetes is associated with an improvement in both left and right ventricular function assessed at echocardiography. These data may explain potential anti‐remodelling effects of gliflozins. [ABSTRACT FROM AUTHOR]

Background: The sodium–glucose cotransporter-2 inhibitors (SGLT2i) have emerged as a crucial therapeutic option for patients with chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single centre, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods: Consecutive patients affected by chronic heart failure (CHF) were evaluated beginning in January 2022. At the baseline clinical visit, both the patient's current medication and the prescribed treatments were recorded. Over a 6- to 12-month follow-up, changes in concomitant therapy were analysed. Results: At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i: 13 with HFrEF, five with mildly reduced (HFmrEF), preserved (HFpEF) or improved (HFimpEF) ejection fraction. After the baseline assessment, SGLT2i were prescribed to 224 (64%) of the patients, including 179 (84%) with HFrEF, 27 (42%) with HFmrEF/HFimpEF, and 18 (22%) with HFpEF/HFimpEF. After follow-up, SGLT2i therapy was well tolerated and was associated with a significant increase in sacubitril/valsartan prescriptions and a decrease in diuretic use. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions: In this single-centre, real-world study, SGLT2i were primarily prescribed to HFrEF patients who were already on other recommended drug classes for their treatment. Additionally, there was a noticeable enhancement in the prescribed therapy during a short-term follow-up. These findings further bolster the inclusion of this therapeutic approach in regular clinical practice. [ABSTRACT FROM AUTHOR]

In heart failure with reduced ejection fraction, edema and congestion are related to reduced cardiac function. Edema and congestion are further aggravated by chronic kidney failure and pulmonary abnormalities. Furthermore, together with edema/congestion, sodium/water retention is an important sign of the progression of heart failure. Edema/congestion often anticipates clinical symptoms, such as dyspnea and hospitalization; it is associated with a reduced quality of life and a major risk of mortality. It is very important for clinicians to predict the signs of congestion with biomarkers and, mainly, to understand the pathophysiological findings that underlie edema. Not all congestions are secondary to heart failure, as in nephrotic syndrome. This review summarizes the principal evidence on the possible roles of the old and new congestion biomarkers in HFrEF patients (diagnostic, prognostic, and therapeutic roles). Furthermore, we provide a description of conditions other than congestion with increased congestion biomarkers, in order to aid in reaching a differential diagnosis. To conclude, the review focuses on how congestion biomarkers may be affected by new HF drugs (gliflozins, vericiguat, etc.) approved for HFrEF. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorder (NMOSD) is a devastating antibody-mediated condition of the central nervous system. As in other autoimmune diseases, there is considerable evidence to suggest that NMOSD arises from complex interactions between genetic susceptibility and environmental factors. However, whether factors like aquaporin-4-Antibody production initiate NMOSD attacks, currently remains unclear, and requires further investigation. Infectious diseases have also been proposed as possible environmental factors associated with NMOSD onset or relapses, some of which are more common in Asia and Latin America than in Europe and North America, in parallel with the higher incidence of NMOSD in these geographic locations. In this review, we examine current evidence on specific infections and vaccines associated with NMOSD onset and/or attacks, as well as the most recent data on gut microbiome composition and SARS-CoV-2 infection in NMOSD patients. [ABSTRACT FROM AUTHOR]

Purpose: To assess the cost-effectiveness and clinical efficacy of AI-assisted abdominal CT-based opportunistic screening for atherosclerotic cardiovascular (CV) disease, osteoporosis, and sarcopenia using artificial intelligence (AI) body composition algorithms. Methods: Markov models were constructed and 10-year simulations were performed on hypothetical age- and sex-specific cohorts of 10,000 U.S. adults (base case: 55 year olds) undergoing abdominal CT. Using expected disease prevalence, transition probabilities between health states, associated healthcare costs, and treatment effectiveness related to relevant conditions (CV disease/osteoporosis/sarcopenia) were modified by three mutually exclusive screening models: (1) usual care ("treat none"; no intervention regardless of opportunistic CT findings), (2) universal statin therapy ("treat all" for CV prevention; again, no consideration of CT findings), and (3) AI-assisted abdominal CT-based opportunistic screening for CV disease, osteoporosis, and sarcopenia using automated quantitative algorithms for abdominal aortic calcification, bone mineral density, and skeletal muscle, respectively. Model validity was assessed against published clinical cohorts. Results: For the base-case scenarios of 55-year-old men and women modeled over 10 years, AI-assisted CT-based opportunistic screening was a cost-saving and more effective clinical strategy, unlike the "treat none" and "treat all" strategies that ignored incidental CT body composition data. Over a wide range of input assumptions beyond the base case, the CT-based opportunistic strategy was dominant over the other two scenarios, as it was both more clinically efficacious and more cost-effective. Cost savings and clinical improvement for opportunistic CT remained for AI tool costs up to $227/patient in men ($65 in women) from the $10/patient base-case scenario. Conclusion: AI-assisted CT-based opportunistic screening appears to be a highly cost-effective and clinically efficacious strategy across a broad array of input assumptions, and was cost saving in most scenarios. [ABSTRACT FROM AUTHOR]

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR−). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (−9.7 ± 5.2% vs. −7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined. [ABSTRACT FROM AUTHOR]

Left ventricular ejection fraction (LVEF) is universally accepted as a cardiac systolic function index and it provides intuitive interpretation of cardiac performance. Over the last two decades, it has erroneously become the leading feature used by clinicians to characterize the left ventricular function in heart failure (HF). Notably, LVEF sets the basis for structural and functional HF phenotype classification in current guidelines. However, its diagnostic and prognostic role in patients with preserved or mildly reduced contractile function is less clear. This is related to several concerns due to intrinsic technical, methodological and hemodynamic limitations entailed in LVEF measurement that do not describe the chamber's real contractile performance as expressed by pressure volume loop relationship. In patients with HF and preserved ejection fraction (HFpEF), it does not reflect the effective systolic function because it is prone to preload and afterload variability and it does not account for both longitudinal and torsional contraction. Moreover, a repetitive measurement could be assessed over time to better identify HF progression related to natural evolution of disease and to the treatment response. Current gaps may partially explain the causes of negative or neutral effects of traditional medical agents observed in HFpEF. Nevertheless, recent pooled analysis has evidenced the positive effects of new therapies across the LVEF range, suggesting a potential role irrespective of functional status. Additionally, a more detailed analysis of randomized trials suggests that patients with higher LVEF show a risk reduction strictly related to overall cardiovascular (CV) events; on the other hand, patients experiencing lower LVEF values have a decrease in HF-related events. The current paper reports the main limitations and shortcomings in LVEF assessment, with specific focus on patients affected by HFpEF, and it suggests alternative measurements better reflecting the real hemodynamic status. Future investigations may elucidate whether the development of non-invasive stroke volume and longitudinal function measurements could be extensively applied in clinical trials for better phenotyping and screening of HFpEF patients. [ABSTRACT FROM AUTHOR]

The 2018 Lancet series on low back pain (LBP) provides a compelling call for action, advocating system-wide transformation of how patients, providers, payers, and society approach the management of chronic LBP (CLBP). To compare outcomes of an interprofessional CLPB program, which utilizes multidimensional risk assessment to provide individualized, low-cost, evidence-based management strategies. Provincial program evaluation from Ontario, Canada. CLBP pilot (2012-17) to full-scale provincial implementation (2018-23). Patient experience/satisfaction surveys; key program/provider performance indicators. The program is a shared-care model, aimed at enabling patients and their primary care providers (PCPs) from diverse geographies and socioeconomic populations to better understand and manage CLPB. A networked provider approach is utilized to align primary to tertiary care guideline-concordant education, self-management exercises, and referral recommendations as required. Adults with unmanageable LBP for 6 weeks to 12 months are eligible for a standardized 1-hour assessment using validated risk tools and receive individualized management recommendations by geographically proximate Advanced Practice Providers (Physiotherapists/Chiropractors). Direct CLBP treatment is not provided. We performed a descriptive evaluation to assess program fidelity from pilot to post full-scale implementation. The pilot program was conducted in a metropolitan, urban and rural/northern population to represent Ontario's geographic and socioeconomic diversity. The pilot supported 540 PCPs and assessed 6,500 referrals (50% had follow visits and 25% underwent additional specialty assessments); demonstrated unprecedented access of less then 4 weeks (vs ≥12 months) from referral (virtually enabled as required); and >90% of patients (n= > 3,000 surveys) reported high patient experience and satisfaction across all multidimensional questions including the ability to better manage their CLPB. As a result of reduced diagnostic imaging, annual estimated per physician cost avoidance was $4175 in year 2. Surgical referral appropriateness increased to 96% compared to 20-30% prior to the program. 97% of PCPs reported high satisfaction with the program. Consistent annual pilot results across geographies/populations led to ministry of health funding for full-scale implementation across Ontario (population 14 million). Since April of 2018, the number of PCPs enrolled in the program has grown to 8,782. As of October 2023, over 71,000 patients have been assessed (53% had follow-ups and 20% underwent additional specialty assessment). Biopsychosocial risk profiles of patients remained the same as the pilot, as did assessment access times (less than 4 weeks), multidimensional patient experience and satisfaction >90% (>12,000 surveys) and specialty referral appropriateness (> 90%). 33,729 referrals requested "recommend appropriate imaging" (12% proceeded to imaging) and 47,526 requested "indicate need for specialist intervention" (16% had specialist assessment). [ABSTRACT FROM AUTHOR]

During the past decade, research has revealed that the vast community of micro-organisms that inhabit the gut - known as the gut microbiota - is intricately linked to human health and disease, partly as a result of its influence on systemic immune responses. Accumulating evidence demonstrates that these effects on immune function are important in neuroinflammatory diseases, such as multiple sclerosis (MS), and that modulation of the microbiome could be therapeutically beneficial in these conditions. In this Review, we examine the influence that the gut microbiota have on immune function via modulation of serotonin production in the gut and through complex interactions with components of the immune system, such as T cells and B cells. We then present evidence from studies in mice and humans that these effects of the gut microbiota on the immune system are important in the development and course of MS. We also consider how strategies for manipulating the composition of the gut microbiota could be used to influence disease-related immune dysfunction and form the basis of a new class of therapeutics. The strategies discussed include the use of probiotics, supplementation with bacterial metabolites, transplantation of faecal matter or defined microbial communities, and dietary intervention. Carefully designed studies with large human cohorts will be required to gain a full understanding of the microbiome changes involved in MS and to develop therapeutic strategies that target these changes. [ABSTRACT FROM AUTHOR]

Cardiac remodelling is an adverse phenomenon linked to heart failure progression and an important contributor to heart failure severity. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction, being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and β-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling (improving N-terminal pro-B-type natriuretic peptide levels, echocardiographic parameters of reverse cardiac remodelling and right ventricular function in patients with heart failure with reduced ejection fraction) were demonstrated. More recently, hemodynamic consequences of gliflozins, reduced cardiac hydrostatic pressure as a possible cause of ventricular remodelling and hypertrophy were proposed to explain potential anti-remodelling effects of gliflozins. Gliflozins exert their cardioprotective effects by attenuating myofibroblast activity and collagen-mediated remodelling. Another postulated mechanism is represented by the reduction in sympathetic activity, through the reduction in renal afferent nervous activity and the suppression of central reflex mechanisms. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described. In this review, we aimed to provide a wide overview on cardiac remodelling with a particular focus on possible anti-remodelling effects of angiotensin receptor neprilysin inhibitors and gliflozins. [ABSTRACT FROM AUTHOR]

Knowledge of the safety and efficacy of disease-modifying therapies (DMTs) in older patients with Multiple Sclerosis (pwMS) is limited due to their exclusion from clinical trials. Our purpose is to evaluate the choice of DMTs in pwMS older than 50 years old in a real-world setting. Cross-sectional study of pwMS from the Argentine MS and NMOSD Registry. We included patients under 35 and above 50 years old prescribed DMTs. Disease activity was categorized as highly active (HA) or not highly active (NHA), and DMTs were classified as low efficacy therapies (LET) or high efficacy therapies (HET). 1460 patients (65% females) were enrolled. The HA group comprised 241 patients, 198 young (82.2%) and 43 older (17.8%). The NHA group included 1219 patients, 893 young (73%) and 326 older (27%). In the NHA group, older patients received LET more frequently than younger patients (66% versus 44%; p < 0.01). In the HA group, older patients received LET in 61% of cases, whereas younger patients received HET in 71% (p = 0.01). The study shows the preference of LET in older patients regardless of disease activity. However it does not demonstrate a difference in disability in older patients based on low vs high efficacy DMTs used, probably due to the design of the study. Further longitudinal studies are warranted to address this issue. • Elderly MS patients often receive low-efficacy therapies. • Therapy selection in MS is often age-driven, guided by physician judgment. • It is the first study in Argentina describing MS treatment for older patients. • Design trials carefully to reduce patient age bias. [ABSTRACT FROM AUTHOR]

Background: Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real‐world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging. Methods: Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA class II‐III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy. Results: After 6‐month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, p < 0.001), TAPSE (19 ± 3 vs. 18 ± 3 mm, p < 0.001), RV FAC (38 ± 7 vs. 34 ± 6 mm, p < 0.001), RV S' (12 ± 2 vs. 10 ± 2 cm/s, p < 0.001), RV‐FW‐LS (−20 ± 5 vs. −18 ± 5%, p < 0.001), RV‐4Ch‐LS (−16 ± 5 vs. −14 ± 5%, p < 0.001). At multivariable analysis improvement in RV‐FW‐LS was associated to baseline levels of RV S' (r 0.75, p < 0.01) and RAV (r –0.32, p < 0.05). Conclusions: In a real‐world scenario, 6‐month therapy with S/V was associated with an improved RV function in HFrEF. RV function improvement may be predicted by assessing baseline RV S' and right atrial volume values. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is currently thought to arise by interactions between genetic susceptibility and environmental factors. Infections in general trigger autoimmune responses causing clinical manifestations of disease. However, as a result of regulatory T (Treg)‐ and regulatory B (Breg)‐cell induction, helminth infections tend to dampen disease activity. IL‐35, the newest member of the IL‐12 family, is an inhibitory cytokine composed of an EBI3β chain subunit, and an IL‐12p35 subunit. The aim of this study was to investigate the role of IL‐35 during parasite infections occurring in individuals with MS. Numbers of IL‐35‐producing Breg cells are higher in CSF from helminth‐infected than from uninfected MS subjects, a finding associated with decreased MRI disease activity. Interestingly, stimulation of CD19+ B cells with IL‐35 promotes conversion of these cells to Breg cells producing both IL‐35 and IL‐10. Coculture of B cells from helminth‐infected MS patients inhibits proliferation of Th1 and Th17 myelin peptide‐specific T cells, as well as production of IFN‐γ and IL‐17. Following activation, CD4+CD25+ Treg cells significantly upregulate expression of EBI3 and IL‐12p35 mRNA. Furthermore, CD4+CD25− T cells activated in the presence of IL‐35 induce a population of cells with regulatory function, known as iTR35. Finally, B cells from normal individuals cultured in vitro in the presence of the helminth antigen SEA increase expression of the transcription BATF, IRF4 and IRF8, acquiring a pattern similar to that of IL‐35 Breg cells. These data highlight the important immunoregulatory effects of IL‐35 on both Breg and Treg cells, observed in helminth‐infected MS subjects. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to astrocyte, then oligodendrocytes followed by demyelination and neuronal loss. NMO spectrum disorder (NMOSD) has recently been defined and stratified based on AQP4-ab serology status. Most NMOSD patients experience severe relapses leading to permanent neurologic disability, making suppression of relapse frequency and severity, the primary objective in disease management. The most common treatments used for relapses are steroids and plasma exchange.Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. In the last 2 years however, three pivotal clinical trials have expanded the spectrum of drugs available for NMOSD patients. Phase III studies have shown significant relapse reduction compared to placebo in AQP4-ab-positive patients treated with satralizumab, an interleukin-6 receptor (IL-6R) inhibitor, inebilizumab, an antibody against CD19+ B cells; and eculizumab, an antibody blocking the C5 component of complement. In light of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs, we present this descriptive review, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

An experimental study aimed at the characterization of energy deposition of nanosecond Dielectric Barrier Discharge (ns-DBD) plasma actuators was carried out. Special attention was given on the effect of the thickness and material used for dielectric barrier. The selected materials for this study were polyimide film (Kapton), polyamide based nylon (PA2200), and silicone rubber. Schlieren measurements were carried out in quiescent air conditions in order to observe density gradients induced by energy deposited. Size of heated area was used to qualify the energy deposition coupled with electrical power measurements performed using the back-current shunt technique. Additionally, light intensity measurements showed a different nature of discharge based upon the material used for barrier, for a fixed thickness and frequency of discharge. Finally, a characterisation study was performed for the three tested materials. Dielectric constant, volume resistivity, and thermal conductivity were measured. Strong trends between the control parameters and the energy deposited into the fluid during the discharge were observed. Results indicate that efficiency of energy deposition mechanism relative to the thickness of the barrier strongly depends upon the material used for the dielectric barrier itself. In general, a high dielectric strength and a low volumetric resistivity are preferred for a barrier, together with a high heat capacitance and a low thermal conductivity coefficient in order to maximize the efficiency of the thermal energy deposition induced by an ns-DBD plasma actuator. [ABSTRACT FROM AUTHOR]

Background Ischemic colitis (IC) is caused by a transient hypo-perfusion of the colon leading to mucosal ulcerations, inflammation, and hemorrhage. The primary aim was to identify predictive factors of endoscopic severity of IC. Secondary endpoints were to show epidemiology, clinical presentation, endoscopic findings, and outcomes of IC. Methods In this single-center retrospective analysis, IC was scored according to endoscopy as: grade 1 (hyperemia, <1 cm erosions and non-confluent ulcers); grade 2 (>1 cm superficial, partially confluent ulcers); and grade 3 (deep or diffuse ulcers or necrosis). Then, IC was grouped into low- (grade 1) and high-grade (grades 2 and 3). Significant (P≤0.1) independent factor of severe IC at univariate analysis were entered into multivariate analysis and considered significant at P<0.05. Results 227 patients (male:female 60:167; mean age 72.7±16.2 years) were included. IC was scored as grade 1 in 137/227 (60.4%), grade 2 in 62/227 (27.3%), and grade 3 in 28/227 (12.3%) patients. At univariate analysis, age (74.9 vs. 71.3 years; P=0.09), diabetes (14.4% vs. 12.4%; P=0.09), and leukocytosis or creatinine elevation (74.4% vs. 60.6%; P=0.032) were associated with endoscopic high-grade IC. At multivariate analysis, leukocytosis and creatinine levels remained associated with high-grade IC (44.7% vs. 29.9%; odds ratio 1.92, 95% confidence interval 1.07- 3.52; P=0.030). Conclusions Although confounding factors cannot be excluded due to study design and patients' characteristics, leukocytosis and/or creatinine elevation at hospital admission were significantly related with endoscopic high-grade IC and might be used to stratify patients for the need of endoscopy. [ABSTRACT FROM AUTHOR]

Purpose: Patients affected by heart failure with reduced ejection fraction (HFrEF) receive clinical and functional beneficial effects from treatment with sacubitril/valsartan. However previous studies have shown that patients with an implantable cardioverter defibrillator (ICD) could obtain even greater benefit, but only make up a only a small proportion of patients. In the current study we evaluated the effect of sacubitril/valsartan in patients with an ICD. Methods: Thirty-five outpatients with HFrEF (aged 60 ± 11 years, 28 were males), on optimal medical therapy were studied. All patients received an ICD at least 6 months before enrollment or were non-responders to ICD plus resynchronization (CRT-D). An open-label sacubitril/valsartan treatment was established at the maximum tolerated dose. Clinical assessment, 6-min walk test (6MWT) and echocardiography, were performed during follow-up at 90, 180, and 360 days. Quality of life score and perceived fatigue on exercise were assessed. Results: Clinical conditions dramatically improved in most patients, especially within the first 6 months of therapy (76 % were in NYHA-I and 24 % in NYHA-II at the end of study vs 71 % NYHA-II and 29 % NYHA III at enrollment, p < 0.001). Quality of life and exercise performance significantly improved according to N-terminal pro-brain natriuretic peptide (NT-proBNP) serum levels lowering. Walking distance at 6MWT increased from 274 ± 97 to 389 ± 53 m and walking speed from 0.74 ± 0.27 to 1.07 ± 0.15 m/s (p < 0.001), while oxygen saturation did not differ significantly (from 90 ± 1 % to 91 ± 2 %). More gradual was left ventricular reverse remodeling. Ejection fraction improved mildly (+ 5 points %, p < 0.001). Global longitudinal strain and diastolic function were also assessed over time. Conclusion: Sacubitril/valsartan therapy for HFrEF may lead to significant clinical and functional improvements even in patients with ICD at greater arrhythmic risk. Clinical improvement is obtained within the first 6 months of treatment while reverse remodeling needs more time. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is characterized by higher rates of atrial fibrillation (AF) and endothelial dysfunction (ED). First line anticoagulant therapy in AF is represented by direct oral anticoagulants (DOACs); several patients, however, are still treated with vitamin-K inhibitors. The use of DOACs is associated in previous studies with an improved vascular function. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with CHF and AF shifting from warfarin to DOACs. Forty-three consecutive outpatients were enrolled in the study. FMD was assessed at baseline and after 4 months. Patients were compared according to AC therapy. After the first measurement of FMD, 18 patients "switched" to DOACs because of poor compliance to warfarin therapy or time in therapeutic range, 19 patients continued to use DOACs, 6 warfarin. "Switched" patients to DOACs therapy showed an improved FMD (19.0 ± 6.6% vs 3.8 ± 1.3%, p < 0.0001); C-reactive protein (CRP) levels decreased in "switched" patients from 1.4 ± 0.5 to 1.0 ± 0.7 mg/dl (p < 0.05). FMD and CRP changes were not significant in patients who did not changed anticoagulant therapy. In switched patients, changes in CRP levels were proportional to FMD changes (r = −0.50, p < 0.05). Shifting from warfarin to DOACs was significantly correlated to improved FMD levels even at multivariable analysis (p < 0.05). Switch from warfarin to DOACs in patents with CHF and AF was associated in an observational non randomized study with an improved endothelial function. Changes in FMD values were related to changes in CRP levels. • Switch from warfarin to DOACs in patients with CHF and AF was associated in an observational non randomized study with an improved endothelial function. • Changes in FMD values were related to changes in CRP levels. • Anticoagulation with DOACs may be preferable over warfain in patients with CHF and AF. [ABSTRACT FROM AUTHOR]

Background: SARS-Cov2 infection may trigger lung inflammation and acute-respiratory-distress-syndrome (ARDS) that requires active ventilation and may have fatal outcome. Considering the severity of the disease and the lack of active treatments, 14 patients with Covid-19 and severe lung inflammation received inhaled adenosine in the attempt to therapeutically compensate for the oxygen-related loss of the endogenous adenosine→A2A adenosine receptor (A2AR)-mediated mitigation of the lung-destructing inflammatory damage. This off label-treatment was based on preclinical studies in mice with LPS-induced ARDS, where inhaled adenosine/A2AR agonists protected oxygenated lungs from the deadly inflammatory damage. The treatment was allowed, considering that adenosine has several clinical applications. Patients and treatment: Fourteen consecutively enrolled patients with Covid19-related interstitial pneumonitis and PaO2/FiO2 ratio<300 received off-label-treatment with 9 mg inhaled adenosine every 12 hours in the first 24 hours and subsequently, every 24 days for the next 4 days. Fifty-two patients with analogue features and hospitalized between February and April 2020, who did not receive adenosine, were considered as a historical control group. Patients monitoring also included hemodynamic/hematochemical studies, CTscans, and SARS-CoV2-tests. Results: The treatment was well tolerated with no hemodynamic change and one case of moderate bronchospasm. A significant increase (> 30%) in the PaO2/FiO2-ratio was reported in 13 out of 14 patients treated with adenosine compared with that observed in 7 out of52 patients in the control within 15 days. Additionally, we recorded a mean PaO2/FiO2-ratio increase (215 ± 45 vs. 464 ± 136, P = 0.0002) in patients receiving adenosine and no change in the control group (210±75 vs. 250±85 at 120 hours, P>0.05). A radiological response was demonstrated in 7 patients who received adenosine, while SARS-CoV-2 RNA load rapidly decreased in 13 cases within 7 days while no changes were recorded in the control group within 15 days. There was one Covid-19 related death in the experimental group and 11in the control group. Conclusion: Our short-term analysis suggests the overall safety and beneficial therapeutic effect of inhaled adenosine in patients with Covid-19-inflammatory lung disease suggesting further investigation in controlled clinical trials. [ABSTRACT FROM AUTHOR]

Spinal hematoma following neuraxial or perineural techniques is a rare but severe complication that can potentially lead to catastrophic consequences. The aim of this review is to analyze all reported cases of neuraxial or perineural bleeding after performance of a locoregional technique since the last guidelines update in 201 8. We included articles indexed by MEDLINE, Scopus, and Google Scholar. We analyzed the patient's age, surgical procedure, pre-operative anticoagulant and antiplatelet therapy, type of anesthetic procedure, vertebra level of the procedure, diameter and point type of the needle, hematoma type (spinal, subdural, epidural), signs and symptoms, time to imaging, and time to treatment and outcome. During our bibliographic research, we identified 5637 unique articles that were eligible according to our protocol criteria, identifying 18 separate cases of neuraxial bleeding. Although clinicians are usually aware of antiplatelet and anticoagulant perioperative management, a careful post-procedural observation and a detailed patient education are also imperative for the early detection of the symptoms of spinal cord ischemia. [ABSTRACT FROM AUTHOR]

In this study, life‐history traits (maximum and average size, size at maturity and fecundity) of two congeneric smooth‐hounds, Mustelus mustelus and Mustelus punctulatus, which share a geographical distribution and experience a similar fishing exploitation, were estimated and compared between species. The results indicated a lower maximum and average size, a lower size at maturity and a higher fecundity in M. punctulatus compared with those in M. mustelus. Considering that these two species co‐occur in the same areas and are caught by the same fishing gears, the results indicate a higher vulnerability to exploitation of M. mustelus compared with that of M. punctulatus. [ABSTRACT FROM AUTHOR]

• Many associated conditions could potentially impairs HF course and prognosis. They can be distinguished in cardiac and extra cardiac comorbidities. • Cardiac comorbidities are strictly related with HF syndrome and are either the cause of clinical deterioration and the primary driver of HF syndrome. • Extra cardiac conditions reflect much more the whole clinical status, systemic organ damage and perfusion. An increased number of extracardiac diseases is often associated with more advanced NYHA class. • Because patients with advanced HF are more often affected by systemic diseases, specific research and management should be addressed in order to better understand mechanisms for each condition. • An holistic view looking at monitorization and specific treatment of each comorbidity could lead to a significant improvement of clinical status and likely to the quality of life. The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities' effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in "fight against heart failure." [ABSTRACT FROM AUTHOR]

Studies the production of ArN[sub +] starting from the two symmetric charge-state reactants Ar[sub +] + N[sub 2] and N[sub 2][sup +] + Ar. Measurement of the total cross sections for both reactions as a function of the relative energy; Explanation for the discrepancies between different estimates of the dissociation energy of ArN[sup +].

The mechanism of action of SGLT2i in HF is different from that of other HF therapies that focused on reverse left ventricular remodeling, blocking the neurohormonal activation (such as renin-angiotensin-aldosterone system inhibitors), or enhancing the natriuretic peptide system (such as neprilysin inhibitors) [[4]]. Current guidelines propose therapeutic algorithms based on left ventricular ejection fraction values and clinical presentations; however, these guidelines do not specify which of the four pillar drugs to start first. However, considering the most recent updates on SGLT2i, I would compare SGLT2i to ACE-inhibitors rather than statins, mainly due to nephroprotection and the multitarget action of ACE-inhibitors and SGLT2i. [Extracted from the article]

The noble gases He, Ne and Ar in fluid inclusions from mantle xenoliths at three localities in Northern Victoria Land (Baker Rocks, Greene Point and Handler Ridge), spanning about 300 km, provide new constraints on the nature of the lithospheric mantle beneath the West Antarctic Rift System (WARS). Mantle xenoliths are anhydrous and hydrous spinel-bearing lherzolite and harzburgite samples. The 4He/40Ar* ratios (0.004–0.39) in olivines, two pyroxenes and amphiboles are much lower than those typical of fertile mantle (1–5), suggesting that this lithospheric domain are consistent with a variably depleted mantle, as also indicated by the major- and trace-element compositions of whole rock and minerals. The 3He/4He ratios vary from 2.30 to 19.79 Ra. However, the lowest and highest 3He/4He ratios are related to the post-eruptive accumulation of radiogenic 4He and cosmogenic 3He, respectively. After filtering the data for these secondary effects, we constrain the 3He/4He signature of the subcontinental lithospheric mantle below this area to 7.1 ± 0.4 Ra (mean ± standard deviation). This isotope signature results from mantle metasomatism by asthenospheric melts with a MORB (mid-ocean ridge basalt)-type 3He/4He. The range of 7.1 ± 0.4 Ra is compatible with previous measurements in mantle xenoliths and lavas from other localities of the NVL, as far away as Mount Erebus, evidencing a homogeneous He-isotope signature beneath the entire rift. The He and Ne isotopes support the hypothesis that WARS origin is not related to a plume. • The mantle source below the WARS is characterized by a homogeneous SCLM-type isotopic helium. • The mantle source below the WARS suffers the influence of rising MORB-type asthenospheric melts. • Lower mantle plume influence below this area is unlikely. • The isotopic helium signature of the WARS mantle source is homogeneous over a distance of thousands of kilometers. [ABSTRACT FROM AUTHOR]

Summary: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting young people and leading to demyelination and neurodegeneration. The disease is clearly more common in women, in whom incidence has been rising. Gender differences include: earlier disease onset and more frequent relapses in women; and faster progression and worse outcomes in men. Hormone‐related physiological conditions in women such as puberty, pregnancy, puerperium, and menopause also exert significant influence both on disease prevalence as well as on outcomes. Hormonal and/or genetic factors are therefore believed to be involved in regulating the course of disease. In this review, we discuss clinical evidence for the impact of sex hormones (estrogens, progesterone, prolactin, and testosterone) on MS and attempt to elucidate the hormonal and immunological mechanisms potentially underlying these changes. We also review current knowledge on the relationship between sex hormones and resident CNS cells and provide new insights in the context of MS. Understanding these molecular mechanisms may contribute to the development of new and safer treatments for both men and women. Hormonal and/or genetic factors are believed to be involved in regulating the course of MS. In this review, we discuss clinical evidence for the impact of sex hormones (estrogens, progesterone, prolactin, and testosterone) on MS and attempt to elucidate hormonal and immunological mechanisms potentially underlying these changes. We also review current knowledge on the relationship between sex hormones and resident CNS cells and provide new insights in the context of MS. [ABSTRACT FROM AUTHOR]

Poly(carbon diselenide), (CSe2)x, is obtained as a black powder either by thermal polymerization of CSe2 solutions at high pressure, slow thermal polymerization under ambient conditions of neat CSe2, or photopolymerization of CSe2 solutions. X-ray diffraction measurements indicate that the as-prepared polymer is highly disordered and does not contain free crystalline or amorphous selenium. This result contrasts with the extensive formation of free selenium in the high pressure, high temperature polymerization of neat CSe2. The electrical conductivity is below 10-6 S cm-1, which is consistent with a band gap of ∼2 eV obtained by diffuse reflection spectroscopy. Details of the thermal properties, and the optical absorption, electron spin resonance, infrared absorption, Raman scattering, and extended x-ray absorption fine structure (EXAFS) spectra of the polymer are discussed. The EXAFS data clearly indicate that Se–Se bonds (but not Se chains) are present. The resonance-enhanced Raman and infrared absorption spectra are consistent with the presence of conjugated carbon–carbon and C=Se bonds, respectively. Based on these results, the structure indicated for (CSe2)x is the head-to-head polymer Se || [–Se–Se–C–C–]n, || Se rather than the head-to-tail polymer Se Se || || [–C–Se–C–Se–]n, proposed by previous workers. This polymer thermally decomposes above about 130 °C to form trigonal selenium as a by-product. [ABSTRACT FROM AUTHOR]

Spinal cord and brain MRI should be routinely performed during follow-up in patients with NMOSD - Yes Brain and spinal cord magnetic resonance imaging (MRI) have a critical role in the early diagnosis of neuromyelitis optica spectrum disorders (NMOSDs) and in its differentiation from multiple sclerosis (MS) and other central nervous system inflammatory conditions, particularly in aquaporin-4-antibodies (AQP4-ab) negative patients.[1],[2] Brain abnormalities have been described in up to 80% of NMOSD patients at presentation, and around 50% are suggestive or typical of NMOSD,[1],[2] frequently located in: optic nerve (bilateral, posterior/chiasmal or longitudinally extensive lesions), brainstem periependymal lesions, periependymal lesions along lateral ventricles, diencephalic lesions, large cortico-spinal tract lesions, and hemispheric lesions.[1] On the other hand, longitudinally extensive myelitis (LETM) on spinal MRI has been reported in up to 70% of NMOSD, while short-segment myelitis (STM) in around 15%-20%.[1][2]-[3] Although the use of contrast may help distinguish NMOSD MRI lesions from other inflammatory diseases, gadolinium administration at follow-up may not be routinely required, particularly if no lesions are detected.[3] After NMOSD diagnosis has been made, MRI longitudinal monitoring of the disease and its association with clinical disability is still not well established. In addition, 17% of the patients did not exhibit any significant brain symptoms but showed chronic NMOSD-typical lesions on MRI.[7] The most common asymptomatic abnormalities included edematous corpus callosum lesions followed by internal capsule and/or cerebral peduncle lesions. [Extracted from the article]

The use of Activated Carboxylic Acids (ACAs) allows the time‐controlled operation of dissipative chemical systems based on the acid‐base reaction by providing both the stimulus that temporarily drives a physicochemical change and, subsequently, the counter‐stimulus with a single reagent addition. However, their application is inherently limited to acid‐sensitive systems. To overcome this limitation, we herein develop a straightforward device for the transduction of the acid‐base stimuli delivered by an ACA into a voltage signal that, in turn, is used to control voltage‐sensitive circuits that are not pH‐responsive by themselves. The signal transductor can be easily assembled from common laboratory equipment and employs aqueous solutions of readily available chemicals. Furthermore, the operator can simply and intuitively tune the amplitude of the voltage signal, as well as its duration and offset by varying the concentration of the chemical species involved in the transduction process. [ABSTRACT FROM AUTHOR]

Physical activity (PA) improves glycemic control and reduces the risk of chronic diabetes-related complications. Despite this evidence, most people with type 1 diabetes (T1DM) do not regularly exercise, mainly due to fear of hypoglycemia during exercise. Improving knowledge in the management of the pathology during exercise can help to reduce PA limiting factors. The purpose of this study was to evaluate the role of an educational PA camp for patients with T1DM to improve active lifestyle. This study involved T1DM's adults attended an educational camp focused on PA and management of glycaemia during exercise. Subjects filled three questionnaires: International PA Questionnaire (IPAQ), Problem Areas in Diabetes (PAID) and Exercise Motivation Inventory (EMI). Data at baseline and after the camp at 1, 3 and 6 month later were analyzed. 25 type 1 diabetics participated at the camp (41.5 ± 11.49 years, 12 females). Subjects who had higher values of PAID presented lower levels of PA. After 3rd and 6th months improvements in PA level were recorded for both genders. PA increased similarly for subjects with lower and higher PAID. At least, EMI's results show that achieving of "physical well-being" was the mainly motivation to increase PA level. These findings showed a positive impact of educational camp on improvement of PA level. A better knowledge in the management of the diabetes during exercise could lead subjects to a more active lifestyle reducing limitation factors. Finally, our results suggest that PA promotion should be better focused on patients with greater difficulties perception. [ABSTRACT FROM AUTHOR]

The 6-minute walking test (6MWT) is a simple assessment tool to evaluate exercise capacity. The result of the test is the distance that a subject can walk at a constant and normal pace within 6 minutes (6MWD) and reflects the aerobic/fitness performance related to walking function. Use of 6MWT has been relevant to assess exercise tolerance either in healthy children or in patients with, heart, lung and metabolic diseases. Our aim was to find 6MWT reference values in healthy Italian children. The 6MWT was performed in 5614 children aged 6–11 years recruited from primary Italian schools. Age related reference percentiles of the covered distance were gender-modeled. A linear and quadratic regression model was used to predict 6MWT performance. Males walked longer distances than females, respectively 598.8±83.9 m vs 592.1±77.6 m (p = 0.0016). According to the regression analysis, 6MWD was positively related to age, gender and height, while it was negatively related to body weight [(6MWD = -160.16 + 93.35× age (years) -4.05× age2 (years) +7.34× gender (m) +2.12× weight (kg) −2.50× height (cm)]. Reference values were established for the 6MWT in healthy children. The age related 6MWD percentiles provided a useful tool in the assessment of capacity in 6–11 year children, in fact they may be helpful to evaluate the effect of a given treatment or rehabilitation program and represent a feasible measure as to prevention within the primary school context. It was found a substantial difference from other countries for 6mwd values. In our study, factors such as age, weight and height were relevant for the prediction of 6MWD, similarly to other studies. Therefore, these variables should be taken into account in context of exercise performance. [ABSTRACT FROM AUTHOR]

Eight samples of Pliocenic/Pleistocenic volcanic rocks from the Hyblean area (south-eastern Sicily, Italy) were investigated for noble gases, trace elements, and Sr-Nd isotopes. The samples consist of tholeiitic basalts, basanites, and nephelinites and display a variable Sr-Nd isotopic composition ( 87 Sr/ 86 Sr = 0.70275–0.70284 and 143 Nd/ 144 Nd = 0.51312–0.51316 in the tholeiites; 87 Sr/ 86 Sr = 0.70294–0.70331 and 143 Nd/ 144 Nd = 0.51293–0.51308 in the basanites/nephelinites). Most of the investigated lavas show almost constant 3 He/ 4 He ratios of about 7.0 Ra, except one basanite and one tholeiite-basalt which exhibit 3 He/ 4 He ratios of 3.5 Ra and 8.3 Ra, respectively. The two samples, both characterized by low abundance of gases, are affected by secondary inputs of 4 He and 3 He that led to a wide deviation from the leading value of 7.0 Ra. We suggest that a heterogeneous lithosphere fed the Quaternary volcanism beneath the Hyblean Plateau. This mantle source is featured by a variable Sr-Nd isotopic composition as a consequence of patchy partial melting or cryptic metasomatism events. Its almost constant isotopic helium is due to the homogenizing effect of deep fluids periodically infiltrating the lithosphere. Although the samples show the same He isotope signatures as mantle harzburgite xenoliths from Hyblean Miocenic diatremes, the distribution of some trace element pairs argues against a close geochemical parentage between the Pliocenic-Pleistocenic volcanic rocks and mantle xenoliths. This can be reconciled if the xenoliths come from mantle portions whose trace element distribution was modified by carbonatitic metasomatic melts responsible for the enrichment of incompatible trace elements but not able to carry significant He amounts. [ABSTRACT FROM AUTHOR]

This paper discusses the first geochemical characterization of obsidian fragments from the prehistoric site of Roccapalumba (Palermo, Italy). The Neolithic age of the prehistoric settlement was constrained by pottery and flint tools discovered in the same archaeological context. To define the provenance of the investigated obsidian artifacts major and trace element analyses have been carried out by using scanning electron microscopy (SEM-EDX) and inductively coupled plasma mass spectrometry (LA-ICP-MS). The comparison with literature data of the Central Mediterranean source areas, based on trace elements content and their ratios allow of constraining a provenance of the Roccapalumba obsidians from the Lipari Island. The obsidian lava flow from Gabellotto Valley is the most probable source of volcanic glass at Lipari and also the most exploited in the Mediterranean area for manufactured tools. The obtained results can contribute in reconstructing the trade/exchange and procurement relationships occurred between the prehistoric human groups inhabiting Sicily during Neolithic age. [ABSTRACT FROM AUTHOR]

In their clinical practice, physicians can face heart diseases (chronic or acute heart failure) affecting the liver and liver diseases affecting the heart. Systemic diseases can also affect both heart and liver. Therefore, it is crucial in clinical practice to identify complex interactions between heart and liver, in order to provide the best treatment for both. In this review, we sought to summarize principal evidence explaining the mechanisms and supporting the existence of this complicate cross-talk between heart and liver. Hepatic involvement after heart failure, its pathophysiology, clinical presentation (congestive and ischemic hepatopathy), laboratory and echocardiographic prognostic markers are discussed; likewise, hepatic diseases influencing cardiac function (cirrhotic cardiomyopathy). Several clinical conditions (congenital, metabolic and infectious causes) possibly affecting simultaneously liver and heart have been also discussed. Cardiovascular drug therapy may present important side effects on the liver and hepato-biliary drug therapy on heart and vessels; post-transplantation immunosuppressive drugs may show reciprocal cardio-hepatotoxicity. A heart-liver axis is drafted by inflammatory reactants from the heart and the liver, and liver acts a source of energy substrates for the heart. [ABSTRACT FROM AUTHOR]

Background Right heart catheterization ( RHC) is usually required to confirm the diagnosis of pulmonary artery hypertension ( PAH). As an invasive test, RHC may be associated with possible complications, so noninvasive parameters able to predict PAH at RHC would be extremely useful. Aim To ascertain possible correlations between cardiopulmonary exercise testing ( CPET) and hemodynamic parameters at RHC indicative of pulmonary hypertension ( PH). Methods Thirty-six consecutive outpatients with suspect of PAH underwent CPET and RHC; the intercept of ventilation (VEint) on the VE vs carbon dioxide production ( VE/ VCO2) and VE/ VCO2 slope at CPET and diastolic pressure gradient ( DPG), trans-pulmonary pressure gradient ( TPG), mean pulmonary artery pressure ( mPAP) and pulmonary vascular resistance ( PVR) at RHC were assessed and compared. Results Ventilation VCO2 slope was directly related to DPG ( r: .41, P: .019), TPG ( r: .45, P: .01), mean pulmonary arterial pressure ( mPAP, r: .36, P: .031), PVR ( r: .41, P: .029), VEint and VE/ VCO2 slope inversely related to DPG ( r: −.63, P < .001), TPG ( r: −.67, P < .001), mPAP ( r: −.68, P < .001) and PVR ( r: −.5, P < .001). Conclusion In patients with suspected PAH, VEint during exercise and the VE/ VCO2 slope might provide useful information to predict results of RHC. Their correlations with PVR and with DPG may be helpful in discriminating patients with isolated postcapillary PH from those with combined postcapillary and precapillary. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) represents one of the main clinical expressions of the vascular changes in systemic sclerosis (SSc). Lung microvascular changes can play a role in the pathogenesis of idiopathic PAH (IPAH) also. The aim of this study is to investigate the presence of capillaroscopic abnormalities in patients with IPAH and to evaluate the differences in capillary nailfold changes between patients with IPAH and patients with SSc with and without PAH. Methods 39 SSc patients (19 with PAH – SSc-PAH and 20 without – SSc-noPAH), 21 subjects with IPAH and 20 healthy subjects were recruited. PAH was diagnosed by right heart catheterization. Nailfold videocapillaroscopy was performed (NVC) in all recruited subjects; capillary quantitative parameters (loops length and width, capillary density, neoangiogenesis) were evaluated and a semiquantitative scoring was used (normal, minor or major abnormalities for healthy controls and IPAH subjects and specific patterns – early, active and late – for SSc subjects) to define microvascular alterations. Results The presence of capillaroscopic abnormalities was detected in 38,1% subjects with IPAH; particularly, compared to healthy controls, capillary density was significantly lower (7,5 ± 1,65 loops/mm vs 9 ± 1,37 loops/mm p < 0,05) and mean capillary width was significantly higher (21 ± 13 μm vs 17 ± 3 μm p < 0,05). A more severe NVC pattern (active/late) was described. SSc-PAH patients compared to SSc-noPAH patients (73,2% vs 50% respectively, p < 0,05), with a significantly lower capillary density (5,64 ± 1,9 loops/mm vs 6,5 ± 1,3 loops/mm p < 0,05) and a significantly higher capillary width (55 ± 7 μm vs 35 ± 8 μm - p < 0,05) and mean number of neoangiogenesis (N/mm) (1 ± 0,33 vs 0,2 ± 0,22 respectively p < 0,05). Conclusions These data, beyond to confirm the role of microvascular damage in SSc-related PAH, support the hypothesis of systemic microvascular involvement in IPAH also, which can be detected by NVC, although further studies are needed to establish whether the changes in the systemic microcirculation are causal or consequential to PAH. [ABSTRACT FROM AUTHOR]

Both proprietary and non-proprietary medicines are expected to undergo rigorous pre-approval testing and both should meet stringent health authority regulatory requirements related to quality to obtain approval. Non-proprietary (also known as copy or generic) medicines, which base their authorization and use on the proprietary documentation and label, are often viewed as a means to help lower cost and thus increase patient access. If these medicines fail to meet quality standards, such as good manufacturing practice and bioequivalence (in humans), they are then defined as substandard copies and can pose serious risks to patients in terms of safety and efficacy. Availability of this type of compounds is more prevalent in regions where health authorities do not enforce registration regulations as stringent as those of the Food and Drug Administration, European Medicines Agency, or World Health Organization, including preestablished quality standard requirements. This article focuses on non-proprietary medicines for multiple sclerosis, that are not identical to proprietary versions and could thus fail to meet efficacy or have different impact on the safety of patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

This study aimed to test acute reactivity during a physical activity in an outdoor setting and to verify the relative perceived performance. In all, 38 volunteers wore accelerometers or not and completed two 20-minute sessions of self-selected pace physical activity. Covered distance, exertional responses, and perceived efficacy were recorded at the end of every session. Relevant finding of this study has been that reactivity to accelerometers also occurs in acute condition. Consequently, this condition leads to a better performance and a greater perceived exertion. Moreover, this situation seems to occur in a state of awareness. [ABSTRACT FROM AUTHOR]

Usually, neurons stimulated by constant current exhibit one of two types of behavior: for type-1 neurons, the curve representing “firing frequency versus input current” is continuous; for type-2 neurons, there is a discontinuity in such a curve. Here, we reproduce these typical behaviors from a discrete-time model based on the dynamics of ion channels. In this model, the axonal membrane is considered as a lattice and each patch of this lattice contains a set of ion channels. The state transitions of the voltage-gated ion channels are governed by deterministic rules. We show that the frequency-current relationship obtained from this model is similar to the one derived from the Hodgkin–Huxley equations, which are commonly used to describe type-2 neurons. We also show that our approach can be convenient to model type-1 neurons. [ABSTRACT FROM AUTHOR]