Microscopic Polyangiitis With Selective Involvement of Central and Peripheral Nervous System : A Case Report

Background: Microscopic polyangiitis (MPA) is a necrotizing vasculitis that affects predominantly small-sized vessels in many organ systems. The disease generally causes glomerulonephritis, pulmonary damage, arthritis, and neuropathy. An exclusive involvement of both central nervous system (CNS) and peripheral nervous system (PNS) is extremely rare. Case Presentation: A 62-year-old woman was admitted to our hospital with a 3 months history of right foot drop, recently complicated by intense myalgia, arthralgia, and allodynia to tactile, vibratory, and pressure stimuli. Since blood tests revealed elevated inflammatory indexes, we suspected either infectious or immune-mediated disorders. Chest radiograph, blood culture series, and echocardiogram revealed normal findings, while urinalysis showed a bacterial infection that was successfully treated. The neurophysiological findings were compatible with multiple mononeuritis, and a brain MRI evidenced ischemic lesions of both basal ganglia and thalamus. A wide-spectrum autoantibody assay revealed the presence of high-titer perinuclear anti-neutrophil cytoplasmic antibodies specific for myeloperoxidase (MPO-ANCA). According to these findings, the diagnosis of MPA was made, and the patient was successfully treated with intravenous (IV) methylprednisolone, followed by two doses of rituximab. Conclusions: An assessment of both CNS and PNS should be included in the diagnostic evaluation of MPA. The involvement of the PNS may raise the risk of a relapsing course and treatment failure, therefore it should be considered in the choice of induction and maintenance therapy

Comprehensive genomic analysis reveals the prognostic role of LRRK2 copy-number variations in human malignancies

Genetic alterations of leucine-rich repeat kinase 2 (LRRK2), one of the most important contributors to familial Parkinson\u2019s disease (PD), have been hypothesized to play a role in cancer development due to demographical and preclinical data. Here, we sought to define the prevalence and prognostic significance of LRRK2 somatic mutations across all types of human malignancies by querying the publicly available online genomic database cBioPortal. Ninety-six different studies with 14,041 cases were included in the analysis, and 761/14,041 (5.4%) showed genetic alterations in LRRK2. Among these, 585 (76.9%) were point mutations, indels or fusions, 168 (22.1%) were copy number variations (CNVs), and 8 (1.0%) showed both types of alterations. One case showed the somatic mutation R1441C. A significant difference in terms of overall survival (OS) was noted between cases harboring somatic LRRK2 whole deletions, amplifications, and CNV-unaltered cases (median OS: 20.09, 57.40, and 106.57 months, respectively; p = 0.0008). These results suggest that both LRRK2 amplifications and whole gene deletions could play a role in cancer development, paving the way for future research in terms of potential treatment with LRRK2 small molecule inhibitors for LRRK2-amplified cases

Quasi-1D hyperbranched WO<inf>3</inf> nanostructures for low-voltage photoelectrochemical water splitting

Arrays of hyperbranched mesostructures self-assembled from the gas phase display a decreased overpotential for the water oxidation reaction.M.B. and A.M. and F.D.F acknowledge financial support from European Union through projects PHOCS, ENERGY 2012- 10.2.1, Future Emerging Technologies Collaborative Project, grant N. 309223. G.D. and C.D. acknowledge funding from the ERC under grant number 259619 PHOTO EM.This is the accepted manuscript. The final version is available at http://pubs.rsc.org/en/Content/ArticleLanding/2015/TA/c4ta06786j#!divAbstract

P473 Histological inflammation in ulcerative colitis in deep remission under treatment with infliximab

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Dental pathology in present-day and copper age samples

Dental paleopathology has become an excellent discipline to reconstruct the oral health of ancient populations and its trend from the past to the present day, especially regarding dietary habits. Our preliminary research aims to perform a comparative analysis on dental health status of two widely chronologically distant samples from Sardinia: the first one dates back to the Copper Age (III mill. B.C.) and comes from a collective hypogean burial named Scab’e Arriu (Siddi, SU), the second one is composed by extracted teeth of present-day individuals, collected during some traineeships at the Department of Surgical Science of the Dentistry School, in Cagliari

Kinetics of Bamberger rearrangement of N-phenylhydroxylamine in a reusable homogeneous system: CH3CN-H2O-CF3COOH

4-Aminophenol is an important raw material for several products in the field of dyes, photographs and pharmaceutics. For instance, paracetamol (N-acetyl-4-aminophenol) a widely employed analgesic and antipyretic [1]. Bases of the present research have been the recent results in the Beckmann rearrangement of the cyclohexanone oxime to caprolactam in CH3CN-CF3COOH solvent catalytic system [2]. The system CH3CN-CF3COOH in that reaction is fully reusable because of the acidity of the CF3COOH does not allow formation of the caprolactam salt and does not need neutralization [2]. Here we study the reactivity of the CH3CN-H2O-CF3COOH system in the Bamberger rearrangement of N-phenylhydroxylamine to 4-aminophenol the former being the key intermediate in the selective hydrogenation of nitrobenzene to 4-aminophenol. The reaction is carried out in a thermostatted reactor and the kinetics has been followed by HPLC and UV-Vis measurements. Both H2O and CF3COOH are in large excess and in any case an apparent first order has been observed, then a first order kobs have been reported. The influence of the operative variable has been studied and in particular the influence of CF3COOH and H2O concentration on reaction rate is shown in Figure 1. The increase of CF3COOH correspond to an increase of the reaction rate, on the contrary H2O inhibits the kinetics. These results suggest that H2O competes in one stage of the rearrangement thus reducing the overall rate, for instance, H2O may influence protonation equilibria

Parkinson's disease in Gaucher disease patients: What's changing in the counseling and management of patients and their relatives?

Background: How to address the counseling of lifetime risk of developing Parkinson's disease in patients with Gaucher disease and their family members carrying a single variant of the GBA1 gene is not yet clearly defined. In addition, there is no set way of managing Gaucher disease patients, taking into account the possibility that they may show features of Parkinson's disease. Methods: Starting from an overview on what has recently changed in our knowledge on this issue and grouping the experiences of healthcare providers of Gaucher disease patients, we outline a path of counseling and management of Parkinson's disease risk in Gaucher disease patients and their relatives. Conclusion: The approach proposed here will help healthcare providers to communicate Parkinson's disease risk to their patients and will reduce the possibility of patients receiving inaccurate information from inadequate sources. Furthermore, this resource will help to empower healthcare providers to identify early signs and/or symptoms of Parkinson's disease and decide when to refer these patients to the neurologist for appropriate specific therapy and follow-up

Loss of the nucleoporin Aladin in central nervous system and fibroblasts of Allgrove Syndrome

Allgrove syndrome (AS) is a rare disease with broad neurological involvement. Neurodegeneration can affect spinal motor neurons, Purkinje cells, striatal neurons, and the autonomic system. The mechanisms that lead to neuronal loss are still unclear. Recessive mutations in the AAAS gene affect the encoded protein Aladin, which would normally localize to the cytoplasmic face of the nuclear membrane as part of the nuclear pore complex (NPC). While the NPC is known to be a key factor for nucleo-cytoplasmic transport, the precise role of Aladin has not been elucidated yet. Here, we explored the consequences of the homozygous AAAS mutation c.464G&gt;A (p.R155H) in central nervous system tissues and fibroblasts of a novel AS patient presenting motor neuron disease, cerebellar ataxia, and autonomic dysfunction. Neuropathological analyses showed severe loss of motor neurons and Purkinje cells, with significant reduction in the perinuclear expression of Aladin. A reduced amount of protein was detected in the nuclear membrane fraction of the patient's brain. RNA analysis revealed a significant reduction of the transcript AAAS-1, while the AAAS-2 transcript was upregulated in fibroblasts. To our knowledge, this is the first study to demonstrate the effects of AAAS mutations in human central nervous system