HCV RNA Genomic sequences and HCV-E2 glycoprotein in sural nerve biopsies from HCV-infected patients with peripheral neuropathy.

AIMS: Peripheral neuropathy (PN), the major neurological complication of chronic HCV infection, is frequently associated with mixed cryoglobulinaemia (MC) and small-vessel systemic vasculitis. While humoral and cell-mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of HCV remains largely speculative. The possible demonstration of HCV in peripheral nerve tissue would obviously assume important pathogenic implications. METHODS: We studied sural nerve biopsies from 11 HCV-positive patients with neuropathic symptoms: five with and six without MC. In situ hybridization (ISH) and immunofluorescence studies were carried out to detect genomic and antigenomic HCV RNA sequences and HCV-encoded E2-glycoprotein, respectively. RESULTS: Epineurial vascular deposits of E2-glycoprotein were found in four (80%) MC and in two (33.3%) non-MC patients, respectively. These findings were enhanced by the perivascular deposition of positive-, though not negative-strand replicative RNA, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and/or complement proteins were revealed around small vessels, without distinct vasculitis changes between MC and non-MC patients. CONCLUSIONS: These results indicate that nerve vascular HCV RNA/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically HCV-infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate HCV productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus-triggered immune-mediated mechanisms.

Activation-induced cytidine deaminase in B cells of hepatits C virus-related cryoglobulinaemic vasculitis.

Immunoglobulin variable region heavy chain (IgVH ) somatic gene diversification is instrumental in the transformation process that characterizes hepatitis C virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to which activation-induced cytidine deaminase (AID), an enzyme essential for IgV gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV) remains unclear. AID mRNA expression in the peripheral blood of 102 chronically hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26 healthy subjects was investigated using real-time reverse transcription-polymerase chain reaction (RT-PCR). The features of activation-induced cytidine deaminase (AID) protein and mRNA transcripts were explored in liver tissue biopsies and portal tracts isolated using laser capture microdissection. In chronically HCV-infected patients, AID mRNA expression was almost threefold higher in those with than in those without CV and sevenfold higher than in healthy subjects (median-fold: 6.68 versus 2.54, P = 0.03 and versus 0.95, P = 0.0003). AID transcript levels were significantly higher in polyclonal than in clonally restricted B cell preparations in either CV or non-CV patients (median-fold, 15.0 versus 2.70, P = 0.009 and 3.46 versus 1.58, P = 0.02, respectively). AID gene expression was found to be related negatively to age and virological parameters. AID protein was found in portal tracts containing inflammatory cells that, in several instances, expressed AID mRNA transcripts. Our data indicate that the aberrant expression of AID may reflect continuous B cell activation and sustained survival signals in HCV-related CV patients.

T cell receptor variable ß gene repertoire in liver and peripheral blood lymphocytes of chronically hepatitis C virus-infected patients with and without mixed cryoglobulinaemia.

To characterize the repertoire of T lymphocytes in chronically hepatitis C virus (HCV)-infected patients with and without mixed cryoglobulinaemia (MC). T cell receptor (TCR) variable (V) ß clonalities in portal tracts isolated from liver biopsy sections with a laser capture microdissection technique in 30 HCV-positive MC patients were studied by size spectratyping. Complementarity-determining region 3 (CDR3) profiles of liver-infiltrating lymphocytes (LIL) were also compared with those circulating in the blood. The representative results of TCR Vß by CDR3 were also obtained from liver tissues and peripheral blood lymphocytes (PBL) of 21 chronically HCV-infected patients without MC. LIL were highly restricted, with evidence of TCR Vß clonotypic expansions in 23 of 30 (77%) and in 15 of 21 (71%) MC and non-MC patients, respectively. The blood compartment contained TCR Vß expanded clones in 19 (63%) MC and 12 (57%) non-MC patients. The occurrence of LIL clonalities was detected irrespective of the degree of liver damage or circulating viral load, whereas it correlated positively with higher levels of intrahepatic HCV RNA. These results support the notion that TCR Vß repertoire is clonally expanded in HCV-related MC with features comparable to those found in chronically HCV-infected patients without MC.

Accuracy evaluation of the Kinect v2 sensor during dynamic movements in a rehabilitation scenario.

In this paper, the accuracy evaluation of the Kinect v2 sensor is investigated in a rehabilitation scenario. The accuracy analysis is provided in terms of joint positions and angles during dynamic postures used in low-back pain rehabilitation. Although other studies have focused on the validation of the accuracy in terms of joint angles and positions, they present results only considering static postures whereas the rehabilitation exercise monitoring involves to consider dynamic movements with a wide range of motion and issues related to the joints tracking. In this work, joint positions and angles represent clinical features, chosen by medical staff, used to evaluate the subject's movements. The spatial and temporal accuracy is investigated with respect to the gold standard, represented by a stereophotogrammetric system, characterized by 6 infrared cameras. The results provide salient information for evaluating the reliability of Kinect v2 sensor for dynamic postures.

[Determination of centric relation. Study of the lateral position of the mandible in relation to the facial median line, using 2 methods of determination]. / Determinação da relação central. Estudo sobre as posições laterais da mandíbula, em relação à linha mediana facial, em função de dois métodos para esta determinação.

The authors studied the lateral positional desviations of the mandible, in relation to the facial median line in 30 (thirty) full edentulous patients, with the purpose to verify the influence of the unstrained guided (chinpoint guidance) and deglutition methods for the determination of centric relation. According the results obtained they conclude that the unstrained guided method produced a mandibular lateral desviation with a mean value of the 0.752 mm and in the deglutition method the mean value observed was 1.109 mm. The statistical analysis of the results revealed for the unstrained guided method a proportion of the "points" to the right and left of the median line not statistically significant, while for the deglutition method the difference was statistically significant at a level of 5%.

[1,3-Bis(diphenylphosphino)propane]trichlorooxorhenium(V).

Trichlorooxo[1,3-propanediylbis(diphenylphosphine)-P,P ']rhenium(V), [ReCl(3)O(C(27)H(26)P(2))], crystallizes with four formula units per unit cell. The crystal structure consists of neutral complexes of [ReOCl(3)(dppp)] [dppp is 1,3-bis(diphenylphosphino)propane] packed by H.pi-ring interactions. The Re atom is octahedrally coordinated to the oxo anion, three Cl atoms and two P atoms from the dppp ligand. The six-membered ring formed by the bidentate dppp ligand and the rhenium metal centre is in a chair conformation. The title compound is an intermediate in the synthesis of bis(dppp) complexes of rhenium.