Il fenomeno dell'elusione fiscale. Fattispecie applicative nei casi di fusione societaria.

Il presente lavoro si pone, nella parte iniziale, l'obiettivo di distinguere il fenomeno dell'elusione fiscale rispetto ad altri comportamenti volti ad ottenere un risparmio d'imposta, ovvero finalizzati alla violazione di specifiche norme fiscali, individuandone i caratteri fondamentali nonché le cause determinanti, per poi approfondire l'indagine con riferimento agli strumenti predisposti dal legislatore italiano per contrastare fenomeni di elusione nazionale ed internazionale. Successivamente, analizzando l'iter evolutivo della normativa in materia di elusione fiscale in ambito nazionale, è possibile evincere il tentativo del legislatore italiano di contrastare tale fenomeno, costantemente in evoluzione, attraverso norme non sempre omogenee ma aventi come denominatore comune la volontà di contrastare l'agire fraudolento del soggetto economico, che pone in essere atti formalmente ossequiosi della norma positiva ma in realtà finalizzati all'ottenimento di un indebito risparmio d'imposta: è qui che risulterà interessante confrontare l'approccio che nel tempo ha adottato il legislatore italiano rispetto a quello degli altri Paesi europei, gran parte dei quali hanno inteso trattare il fenomeno elusivo equiparandolo al concetto di abuso del diritto. L'ultimo capitolo invece, avrà l'obiettivo di individuare le caratteristiche principali di tale fenomeno, ponendo l'attenzione sulle possibili operazioni elusive contemplate dall'articolo 37 bis, terzo comma del D.P.R. n. 600/1973, in particolare soffermandosi sulla fattispecie tassativamente prevista dallo stesso, quale l'operazione di fusione societaria, tramite l'analisi di alcuni casi specifici

Acrodermatitis chronica atrophicans of the face: a case report and a brief review of the literature.

Acrodermatitis chronica atrophicans is a rare late manifestation of tick-borne Borrelia burgdorferi infection, manifesting as inflammatory and atrophic lesions on acral skin.We describe the case of  a 73-year-old woman with skin changes progressed to marked atrophy on her left hand and an edematous inflammatory involvement of the face. The diagnosis of acrodermatitis chronica atrophicans was made on the basis of clinical appearance, serological and histopathological findings, and the lesional detection of B. burgdorferi-specific gene segments by polymerase chain reaction.This unusual case illustrates that acrodermatitis chronica atrophicans affects not only the extremities but also the face. The clinical and histological finding of the lesions occurring on acral skin showed a prominent atrophic appearance, while the ones occurring on the face showed a prominent inflammatory appearance..</p

Catastrophic NAD+ Depletion in Activated T Lymphocytes through Nampt Inhibition Reduces Demyelination and Disability in EAE

Nicotinamide phosphoribosyltransferase (Nampt) inhibitors such as FK866 are potent inhibitors of NAD+ synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE) as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD+ depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-γ and TNF-α production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD+-degrading enzyme poly-(ADP-ribose)-polymerase (PARP) by activated T cells enhances their susceptibility to NAD+ depletion. In addition, we relate defective IFN-γ and TNF-α production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors) could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders

Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score

Objective To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. Results The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome. Conclusion The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice

Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry

: To characterize clinical and laboratory signs of patients with still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. patients with still's disease classified according to internationally accepted criteria were enrolled in the autoInflammatory disease alliance (AIDA) still's disease registry. clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p &lt; 0.001), platelet abnormalities (p &lt; 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p &lt; 0.001). at multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Acrodermatitis chronica atrophicans of the face: a case report and a brief review of the literature.

Acrodermatitis chronica atrophicans is a rare late manifestation of tick-borne Borrelia burgdorferi infection, manifesting as inflammatory and atrophic lesions on acral skin. We describe the case of a 73-year-old woman with skin changes progressed to marked atrophy on her left hand and an edematous inflammatory involvement of the face. The diagnosis of acrodermatitis chronica atrophicans was made on the basis of clinical appearance, serological and histopathological findings, and the lesional detection of B. burgdorferi-specific gene segments by polymerase chain reaction. This unusual case illustrates that acrodermatitis chronica atrophicans affects not only the extremities but also the face. The clinical and histological finding of the lesions occurring on acral skin showed a prominent atrophic appearance, while the ones occurring on the face showed a prominent inflammatory appearance

Nampt inhibition with FK866 induces mitochondria depolarization and ATP depletion in activated T lymphocytes.

<p>A, PHA- stimulated PBLs were incubated with 33 nM FK866 and <i>ΔΨ</i>_m was determined at the indicated days of exposure. B, Resting of PHA-stimulated PBLs were cultured with 33 nM FK866 for five days. Thereafter PBLs with conserved <i>ΔΨ</i>_m-high were quantified by flow-cytometry. C, Bcl2-overexpressing Jurkat and the respective vector control cells were incubated with 10 nM FK866 for the indicated number of days. Thereafter, <i>ΔΨ</i>_m was determined. Inset, Western blot for Bcl2 and γ-tubulin expression. D, 5×10⁵ Bcl2-overexpressing Jurkat and the vector control cells were incubated with or without 10 nM FK866 for the indicated times before ATP was detected. ATP levels are presented as % of ATP in FK866-untreated cells. E, 3×10⁴ Bcl2-overexpressing and control Jurkat cells/well were incubated in 96-well plates with or without the indicated FK866 concentrations. Viability was determined by PI staining and flow cytometry 96 h later. F, PHA-stimulated PBLs were incubated in the presence or absence of 33 nM FK866 with or without the indicated concentrations of 3-MA. Viability was detected after five days. *, p<0.05. G, PBLs incubated in 96-well plates in the presence of 5 µg/ml PHA were treated for five days with the indicated FK866 concentrations in the presence or absence of 20 µM LY294002. Viability was subsequently determined by PI staining and flow cytometry. B, Results are presented as means ± SD of three experiments (B, D–G). Panels A and C are representative of three separate experiments.</p

FK866 ameliorates EAE.

<p>10 mg/kg body weight FK866 were administered to mice from day 12 after rMOG immunization for 10 days. A, NAD(H) and NADP(H) levels were measured in mononuclear cells isolated from spleen and lymph nodes of treated or untreated animals at day 16. Dinucleotide levels in FK866-treated mice were expressed as % of those detected in control animals. B, FK866 halts EAE severity compared with controls (p<0.05 from day 19 onward). Arrows indicate the days of FK866 administration. C, Luxol fast Blue staining of the spinal cord shows areas of demyelination in control mice compared with FK866-treated animals.</p