Evaluating hormonal mechanisms of vitamin D receptor agonist therapy in diabetic kidney disease: the VALIDATE-D study

Background: Insufficient vitamin D status and increased renin-angiotensin system (RAS) activity have been associated with renal-vascular disease and nephropathy in diabetes. Accumulating evidence indicates that vitamin D receptor (VDR) activation lowers unfavorable RAS activity; however, more human intervention studies evaluating whether this mechanism could influence diabetic kidney disease are needed. We previously reported that both vitamin D levels and genetic variation at the VDR predict human RAS activity, and that vitamin D therapy can lower RAS activity in non-diabetics. The VALIDATE-D study is a randomized, placebo-controlled, intervention study designed to extend these findings by evaluating whether direct VDR activation in diabetes lowers circulating and local renal-vascular tissue RAS activity (Aims 1 and 2) in a manner similar to the action of ACE inhibitors (Aim 3). Methods/Design Forty subjects with type 2 diabetes, microalbuminuria, and without chronic kidney disease will be recruited to undergo detailed assessment of the RAS before and after randomization to calcitriol 0.75 mcg/day or placebo. Primary analyses will evaluate whether calcitriol therapy reduces circulating and renal-vascular tissue-RAS activity in comparison to placebo. All subjects will thereafter be treated with lisinopril and followed for 3.5 months to evaluate whether combination therapy (calcitriol + lisinopril vs. placebo + lisinopril) additively or synergistically improves renal-vascular function, and lowers proteinuria. Discussion The VALIDATE-D study is the first human intervention study to evaluate whether direct VDR activation can lower the human RAS in diabetes, compared to the effect of an ACE inhibitor, and whether this mechanism can translate to clinically relevant endpoints for diabetic kidney disease. The outcomes of VALIDATE-D will have major implications for the recommendation of vitamin D supplementation for the primary prevention of kidney complications in diabetes. Trial registration ClinicalTrials.gov, NCT0163506

Advanced 3D “Modeling” and “Printing” for the Surgical Planning of a Successful Case of Thoraco-Omphalopagus Conjoined Twins Separation

The surgical separation of two Conjoined Twins is a particularly complex operation. Surgical times are particularly long and post-operative complications are very frequent in this type of procedure. We report a clinical case of surgical separation of two thoraco-omphalopagus conjoined twins in which, thanks to the use of (3D) three dimensional technologies, we were able to significantly reduce operative times and improve clinical outcomes

Utility of adenosine stress perfusion CMR to assess paediatric coronary artery disease

AIMS: Cardiovascular magnetic resonance (CMR), using adenosine stress perfusion and late-gadolinium enhancement (LGE), is becoming the 'gold standard' non-invasive imaging modality in the assessment of adults with coronary artery disease (CAD). However, despite its proved feasibility in paediatric patients, clinical utility has not been demonstrated. Therefore, this study aims to establish the role of adenosine stress perfusion CMR as a screening test in paediatric patients with acquired or congenital CAD. METHODS AND RESULTS: A total of 58 paediatric patients underwent 61 consecutive clinically indicated coronary artery assessments for diagnostic and clinical decision-making purposes. The diagnosis was based on X-ray or computed tomography coronary angiography for anatomy, adenosine stress CMR imaging for myocardial perfusion and LGE for tissue characterization. Two studies were aborted because of unwanted side effects of adenosine stress, thus 59 studies were completed in 56 patients [median age 14.1 years (interquartile range 10.9-16.2)]. When compared with coronary anatomical imaging, adenosine stress perfusion CMR performed as follows: sensitivity 100% (95% confidence interval, CI: 71.6-100%), specificity 98% (95% CI: 86.7-99.9%), positive predictive value (PPV) 92.9% (95% CI: 64.2-99.6%), and negative predictive value 100% (95% CI: 89.9-100%). CONCLUSION: In paediatric CAD, adenosine stress perfusion CMR imaging is adequate as an initial, non-invasive screening test for the identification of significant coronary artery lesions, with anatomical imaging used to confirm the extent of the culprit lesion

Electric vehicles’ consumer behaviours: Mapping the field and providing a research agenda

Research on consumers of electric vehicles appears to offer significant contributions relative to the behaviour factors that stimulate purchase. Although it is one of the topics most endorsed by international organisations, a holistic compendium of the literature is not provided. Therefore, different research directions necessitate a clear systematisation. This study moves in this direction by conducting a bibliometric and thematic analysis of 254 studies related to consumer behaviour in the electric car market. The research reveals the primary co-citation network between international journals and authors, a map of the leading research centres on the topic, and the dimensions covered by scholars. Additionally, the analysis extends the theory of planned behaviour, offering a valuable consumer identikit for practitioners. Based on the results, the study provides multiple research questions helpful to feed the academic debate. © 2022 The Author(s)Horizon 2020 Framework Programme, H2020: 869986This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 869986

Italian Health Care System: Methodology Suggestion for the Financial Equilibrium and Essential Level of Care

Italian Regions are the accountable entities for healthcare policies: their activity is not limited to policymaking but includes also management and financing of the Healthcare Public Utilities and services. A first step will be the creation of a dataset of revenues and expenditures of the Healthcare sector. Second, the cofinancing policy will be analyzed using comparative grids of in/out-flows of each Region. Third, it will be taken into account the regional fiscal coverage of the balance deficit. The sample is composed by the Italian Regions. Last the analysis between our theoretical approach based on law and the real economic balance. Furthermore it will be analyzed the National and Regional Healthcare System financing (in)-stability, highlighting current cash flows, sources and investments using the \u201cseparation\u201d of the Healthcare accounting items in the Balance Sheet. Through chi-square test analysis and method of OLS the group of study look a possible relation be-tween balance and respect of lea without finding a relationship. Latter, it will be represented an analysis of the National Health Fund allocation to the Regions. It will be also conducted a critical analysis of the current allocation formula and it will be proposed a simplified criterion of allocation

Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95% CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies

Piattaforme di Crowdfunding: un modello aziendale a sostegno della cultura in Italia

Secondo una visione di tipo antropologico, le imprese nascono dai bisogni delle persone, soddisfatti secondo un principio di sussidiariet\ue0. Il fenomeno del crowdfunding, oggetto di molti interventi e al centro dell\u2019attenzione mediatica negli ultimi anni, si pu\uf2 collocare in quest\u2019ottica: un soggetto, al fine di soddisfare un suo bisogno (condivisione, appartenenza, accessibilit\ue0, creazione di valore condiviso, visibilit\ue0, supporto, migliore comunicazione) si rivolge a una folla (\u201ccrowd\u201d). A tal fine, le piattaforme di crowdfunding (gestite in parte da soggetti giuridici separati, ma in parte come imprese vere e proprie e a s\ue9 stanti), consentono la soddisfazione del bisogno di supporto finanziario. Per\uf2, sono (o saranno in un futuro prossimo) le piattaforme di crowdfunding idonee a compensare o integrare il finanziamento tradizionale delle opere e produzioni culturali? In questo contributo sono analizzate le principali caratteristiche e i principali studi scientifici sul fenomeno del crowdfunding, in particolare culturale, e sono discusse le dimensioni e le dinamiche del crowdfunding culturale in Italia, con un particolare insight sul territorio piemontese. Nelle conclusioni viene rilevata sia la attuale inadeguatezza del sistema, dovuta in particolare alla sua sostanziale novit\ue0, sia il trend evolutivo, che ne conferma le potenzialit\ue0 future come modello aziendale di supporto al settore culturale, sempre crescente, in Italia