Il controllo giudiziale sulle ragioni economiche di licenziamento

L'elaborato analizza l'evoluzione del controllo giudiziale sulle ragioni economiche di licenziamento, a partire dalla l. n. 604/1966 fino alla recente riforma l. n. 92/2012. Con riferimento al novellato art. 18 St. lav., l'analisi ripercorre le diverse ricostruzioni dottrinali e le prime applicazioni giurisprudenziali, al fine di individuare i limiti del sindacato del giudice

Biomarkers of Parkinson's disease: recent insights, current challenges, and future prospects

Marina Picillo,1 Marcello Moccia,2 Emanuele Spina,2 Paolo Barone,1 Maria Teresa Pellecchia1 1Department of Medicine and Surgery, Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, University of Salerno, Salerno, Italy; 2Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University, Naples, Italy Abstract: A biomarker represents a tool possibly helping physicians in predicting onset, diagnosis, and progression of a disease as well as evaluating the response to disease-modifying treatments. Currently, there is no biomarker fulfilling all such ideal criteria for Parkinson's disease (PD). In this article, we have critically reviewed the literature searching for the most reliable and reproducible clinical, biochemical, and imaging biomarkers for prodromal phase, diagnosis, and progression of PD. Different comprehensive batteries of biomarkers have been proposed as a sensitive approach to predict the onset of PD during the prodromal phase. There is a discussion about the redefinition of the clinical diagnosis of PD, including clinical biomarkers as non-motor symptoms; however, on the other hand, we have also observed that imaging biomarkers support the differential diagnosis from other causes of parkinsonism. Various clinical (eg, freezing of gait or cognitive impairment), biochemical (eg, epidermal growth factor, insulin-like growth factor 1, uric acid, etc), and imaging (eg, functional magnetic resonance imaging, voxel-based morphometry, etc) biomarkers may help envisaging disease progression of PD. To conclude, given the lack of a single biomarker that could track the entire course of the disease, our challenge is to find the best combinations of biomarkers for the different stages of the disease. Keywords: biomarkers, Parkinson's disease, progression, motor, imaging , staging, non moto

Fine tuning of atomic point charges classical simulations of pyridine in different environments

Abstract A correct description of electrostatic contributions in force fields for classical simulations is mandatory for an accurate modeling of molecular interactions in pure liquids or solutions. Here, we propose a new protocol for point charge fitting, aimed to take into the proper account different polarization effects due to the environment employing virtual sites and tuning the point charge within the polarizable continuum model framework. The protocol has been validated by means of molecular dynamics simulations on pure pyridine liquid and on pyridine aqueous solution, reproducing a series of experimental observables and providing the information for their correct interpretation at atomic level

Androgen-stimulated DNA synthesis and cytoskeletal changes in fibroblasts by a nontranscriptional receptor action

In NIH3T3 cells, 0.001 nM of the synthetic androgen R1881 induces and stimulates association of androgen receptor (AR) with Src and phosphatidylinositol 3-kinase (Pl3-kinase), respectively, thereby triggering S-phase entry. 10 nM R1881 stimulates Rac activity and membrane ruffling in the absence of the receptor–Src–PI3-kinase complex assembly. The antiandrogen Casodex and specific inhibitors of Src and PI3-kinase prevent both hormonal effects, DNA synthesis and cytoskeletal changes. Neither low nor high R1881 concentration allows receptor nuclear translocation and receptor-dependent transcriptional activity in fibroblasts, although they harbor the classical murine AR. The very low amount of AR in NIH3T3 cells (7% of that present in LNCaP cells) activates the signaling pathways, but apparently is not sufficient to stimulate gene transcription. This view is supported by the appearance of receptor nuclear translocation as well as receptor-mediated transcriptional activity after overexpression of AR in fibroblasts. In addition, AR-negative Cos cells transiently transfected with a very low amount of hAR cDNA respond to low and high R1881 concentrations with signaling activation. Interestingly, they do not show significant transcriptional activation under the same experimental conditions. Fibroblasts are the first example of cells that respond to steroid hormones with activation of signaling pathways in the absence of endogenous receptor transcriptional activity. The data reported also show that hormone concentration can be crucial in determining the type of cell responsiveness

Pacientes com hepatite C crônica e transaminases normais

Hepatitis C virus infection evolves progressively persisting in the majority of patients (85%). Most patients have high ALT (alanine aminotransferase) levels and approximately 25% normal ALT. The latter are usually female and there is no association between genotype and severity of hepatic lesion. Histologic analysis usually shows small lesion and absence or low amount of fibrosis, despite cirrhosis having been reported. Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we have carried out a study of 68 chronic hepatitis C patients between January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C patients with normal ALT levels, 45.6% of which were male and 54.4% female, the mean age being 38 +/- 13 years. We found a predominance of genotype 1 in 84.7% of the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases liver biopsies revealed liver reaction, periportal activity score 0-1 was observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of them. Periportal activity >; 2 and structural activity >; 1 was seen in 29%, but steatosis was not seen in 73.5%. Our results suggest the need to revisit for liver biopsy practice in patients with Chronic Hepatitis C and normal transaminases.Hepatite C é uma doença de evolução progressiva. A maioria dos pacientes tem nível de ALT elevada e 25% apresentam níveis normais. Os com ALT normal geralmente são do gênero feminino e sem associação entre genótipo e gravidade de lesão hepática. O exame histopatológico mostra geralmente ausência de ou leve fibrose (cerca de 20% tem fibrose), embora cirrose já tenha sido relatada. Visando estimar a prevalência, características demográficas, genotípicas e anatomopatológicas em pacientes com ALT normal, realizamos um estudo de série com 68 casos com diagnóstico de hepatite C crônica. Os pacientes foram selecionados de janeiro de 1977 a abril de 2002. Encontrou-se uma prevalência de 13,8% (45,6% masculinos). A média de idade foi 39 +/- 13 anos. Predomínio de genótipo 1 (84,8%), seguido pelo 3 (8,5%) e 2 (6,7%). Encontramos fígado reacional em 52,9% das biópsias, atividade periportal de 0-1 em 85,3% e atividade periportal de 2-4 em 14,7%. Apresentaram atividade estrutural de 0 a 1 73,5% e 26,5% com atividade estrutural de 2 a 4, sendo que 29% da amostra apresentou APP >; 2 e AE >; 1; 73,5% não apresentaram esteatose. Nossos dados reforçam a necessidade de biópsia em pacientes com hepatite C e níveis de ALT normais

pRb2/p130 localized to the Cytoplasm in Diffuse Gastric Cancer

pRb2/p130 is a key tumor suppressor, whose oncosuppressive activity has mainly been attributed to its ability to negatively regulate cell cycle by interacting with the E2F4 and E2F5 transcription factors. Indeed, pRb2/p130 has been found altered in various cancer types in which it functions as a valuable prognostic marker. Here, we analyzed pRb2/p130 expression in gastric cancer tissue samples of diffuse histotype, in comparison with their normal counterparts. We found a cytoplasmic localization of pRb2/p130 in cancer tissue samples, whereas, in normal counterparts, we observed the expected nuclear localization. pRb2/p130 cytoplasmic delocalization can lead to cell cycle deregulation, but considering the emerging involvement of pRb2/p130 in other key cellular processes, it could contribute to gastric tumorigenesis also through other mechanisms. Our data support the necessity of further investigations to verify the possibility of using pRb2/p130 as a biomarker or potential therapeutic target for diffuse gastric cancer

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS

The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases

IntroductionMinimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilution, several flow cytometry (FC) strategies for hemodilution evaluation have been compared. MethodsFor each BM sample, cells populations with a well-known distribution in BM and peripheral blood - e.g., mast cells (MC), immature (IG) and mature granulocytes (N) - have been studied by FC and quantified alongside the BM differential count. ResultsThe frequencies of cells' populations were correlated to the IG/N ratio, highlighting a mild correlation with MCs and erythroblasts (R=0.25 and R=0.38 respectively, with p-value=0.0006 and 0.0000052), whereas no significant correlation was found with B or T-cells. The mild correlation between IG/N, erythroblasts and MCs supported the combined use of these parameters to evaluate BM hemodilution, hence the optimization of the ALLgorithMM. Once validated, the ALLgorithMM was employed to evaluate the dilution status of BM samples in the context of MRD assessment. Overall, we found that 32% of FC and 52% of Next Generation Sequencing (NGS) analyses were MRD negative in samples resulted hemodiluted (HD) or at least mildly hemodiluted (mHD). ConclusionsThe high frequency of MRD-negative results in both HD and mHD samples implies the presence of possible false negative MRD measurements, impairing the correct assessment of patients' response to therapy and highlighs the importance to evaluate BM hemodilution

Gait Analysis in Progressive Supranuclear Palsy Phenotypes

The objective of the present study was to describe gait parameters of progressive supranuclear palsy (PSP) phenotypes at early stage verifying the ability of gait analysis in discriminating between disease phenotypes and between the other variant syndromes of PSP (vPSP) and Parkinson's disease (PD). Nineteen PSP (10 PSP-Richardson's syndrome, five PSP-parkinsonism, and four PSP-progressive gait freezing) and nine PD patients performed gait analysis in single and dual tasks. Although phenotypes showed similar demographic and clinical variables, Richardson's syndrome presented worse cognitive functions. Gait analysis demonstrated worse parameters in Richardson's syndrome compared with the vPSP. The overall diagnostic accuracy of the statistical model during dual task was almost 90%. The correlation analysis showed a significant relationship between gait parameters and visuo-spatial, praxic, and attention abilities in PSP-Richardson's syndrome only. vPSP presented worse gait parameters than PD. Richardson's syndrome presents greater gait dynamic instability since the earliest stages than other phenotypes. Computerized gait analysis can differentiate between PSP phenotypes and between vPSP and PD