Hepatitis C Virus P7—A Viroporin Crucial for Virus Assembly and an Emerging Target for Antiviral Therapy

The hepatitis C virus (HCV), a hepatotropic plus-strand RNA virus of the family Flaviviridae, encodes a set of 10 viral proteins. These viral factors act in concert with host proteins to mediate virus entry, and to coordinate RNA replication and virus production. Recent evidence has highlighted the complexity of HCV assembly, which not only involves viral structural proteins but also relies on host factors important for lipoprotein synthesis, and a number of viral assembly co-factors. The latter include the integral membrane protein p7, which oligomerizes and forms cation-selective pores. Based on these properties, p7 was included into the family of viroporins comprising viral proteins from multiple virus families which share the ability to manipulate membrane permeability for ions and to facilitate virus production. Although the precise mechanism as to how p7 and its ion channel function contributes to virus production is still elusive, recent structural and functional studies have revealed a number of intriguing new facets that should guide future efforts to dissect the role and function of p7 in the viral replication cycle. Moreover, a number of small molecules that inhibit production of HCV particles, presumably via interference with p7 function, have been reported. These compounds should not only be instrumental in increasing our understanding of p7 function, but may, in the future, merit further clinical development to ultimately optimize HCV-specific antiviral treatments

CROSS-SHAPING – THE MORE EFFECTIVE NORDIC WALKING? RESULTS OF A BIOMECHANICAL FIELD STUDY

Cross-shaping is a new developed kind of nordic walking. The main difference between nordic walking and cross-shaping is the use of special sticks with forearm shells and wheels. The purpose of this study was to analyze the health effects of cross-shaping and to compare the results with own previous studies of nordic walking. Results clearly show positive health effects from cross-shaping, which are more extensive than in walking and nordic walking. Cross-shaping is harmonious similar to cross-country skiing in classic style. Push off is more effective than in nordic walking. Upper body is more erected and spine is relieved and mobilized effectively. Large parts of muscles of the upper and lower extremities were physiologically trained effective. Positive effects on the cardiovascular system are increased considerably compared to walking and nordic walking

Der Cross-Shaper: ein neues Sportgerät zum gesunden und effektiven Ganzkörpertraining – Ergebnisse einer biomechanischen Feldstudie

ZusammenfassungDer Cross-Shaper wurde entwickelt, um in den Bewegungsablauf des Walkens den Oberkörper effektiver einbeziehen zu können. Diese Feldstudie konnte deutlich positive gesundheitliche Effekte des Cross-Shapers zeigen, die umfassender ausgeprägt sind als beim Walking und Nordic Walking. Der Bewegungsverlauf ist harmonisch. Der stoßreduzierte Abdruck ist effektiver als beim Nordic Walking. Der Oberkörper wird vermehrt aufgerichtet und die Wirbelsäule effektiv entlastet und mobilisiert. Weite Teile der Muskulatur werden physiologisch gleichermaßen trainiert. Positive Effekte auf das Herz-Kreislauf-System sind gegenüber Walking und Nordic Walking deutlich erhöht.SummaryThe Cross-Shaper was developed to include the upper body more effectively in the motion sequence of walking. Results of this field study clearly show positive health effects from cross-shaper, which are pronounced more extensive than in walking and nordic walking. The path of movement is harmonious. The shock reduced push off is considerably more effective than in nordic walking. The upper body is increasingly erected and the spine is relieved and mobilized effectively. Large parts of muscles were physiologically trained equally effective. Positive effects on the cardiovascular system are increased considerably compared to walking and nordic walking

HIP- AND BACK-PROTECTORS IN SPORTS AND EVERYDAY LIFE - EFFECTIVE PROTECTION?

Hip and back protectors are recommended to reduce impact forces when falling in sports or everyday life. This study analyzed the shock-reducing effect of 29 different hip and back protectors using a drop test and a Kistler force plate. Our results showed large differences between the single protectors. Measured peak forces often and quickly exceeded the supposed limit of bone fracture strength. Therefore sufficient safety does not seem to exist yet and protectors must not be overestimated in their protection potential. In our opinion protectors should have a certain thickness preferably a combination of hardshell and viscoelastic material. Hip protectors for sports still show large deficits. Back protectors only protect against direct contusion but not against axial compressions or cervical spine

The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation

Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI

Hepatitis C Virus p7 Protein Is Crucial for Assembly and Release of Infectious Virions

Hepatitis C virus (HCV) infection is associated with chronic liver disease and currently affects about 3% of the world population. Although much has been learned about the function of individual viral proteins, the role of the HCV p7 protein in virus replication is not known. Recent data, however, suggest that it forms ion channels that may be targeted by antiviral compounds. Moreover, this protein was shown to be essential for infectivity in chimpanzee. Employing the novel HCV infection system and using a genetic approach to investigate the function of p7 in the viral replication cycle, we find that this protein is essential for efficient assembly and release of infectious virions across divergent virus strains. We show that p7 promotes virus particle production in a genotype-specific manner most likely due to interactions with other viral factors. Virus entry, on the other hand, is largely independent of p7, as the specific infectivity of released virions with a defect in p7 was not affected. Together, these observations indicate that p7 is primarily involved in the late phase of the HCV replication cycle. Finally, we note that p7 variants from different isolates deviate substantially in their capacity to promote virus production, suggesting that p7 is an important virulence factor that may modulate fitness and in turn virus persistence and pathogenesis

Increase in fall-related hospitalizations in the United States, 2001-2008

BACKGROUND: The objective was to determine secular trends in unintentional fall-related hospitalizations in people aged 65 years and older in the United States. MATERIALS: Data were obtained from a nationally representative sample of emergency department visits from January 1, 2001, to December 31, 2008, available through the National Electronic Injury Surveillance System-All Injury Program. These data were weighted to estimate the number, incidence rates, and the annual percent change of fall-related hospitalizations. RESULTS: From 2001 to 2008, the estimated number of fall-related hospitalizations in older adults increased 50%, from 373,128 to 559,355 cases. During the same time period, the age-adjusted incidence rate, expressed per 100,000 population, increased from 1,046 to 1,368. Rates were higher in women compared with men throughout the study period. The age-adjusted incidence rate showed an average annual increase of 3.3% (95% CI, 1.66-4.95). DISCUSSION: Both the number and rate of fall-related hospitalizations in the United States increased significantly over the 8-year study period. Unless preventive action is taken, rising hospitalization rates in combination with the aging US population over the next decades will exacerbate the already stressed healthcare system and may result in poorer health outcomes for older adults in the future. Further research is needed to determine the underlying causes for this rising trend. Copyrigh

Rheumatoid arthritis synovium contains plasmacytoid dendritic cells

We have previously described enrichment of antigen-presenting HLA-DR(+ )nuclear RelB(+ )dendritic cells (DCs) in rheumatoid arthritis (RA) synovium. CD123(+)HLA-DR(+ )plasmacytoid DCs (pDCs) and their precursors have been identified in human peripheral blood (PB), lymphoid tissue, and some inflamed tissues. We hypothesized recruitment of pDCs into the inflamed RA synovial environment and their contribution as antigen-presenting cells (APCs) and inflammatory cells in RA. CD11c(+ )myeloid DCs and CD123(+ )pDCs were compared in normal and RA PB, synovial fluid (SF), and synovial tissue by flow cytometry, immunohistochemistry, and electron microscopy and were sorted for functional studies. Nuclear RelB(-)CD123(+ )DCs were located in perivascular regions of RA, in a similar frequency to nuclear RelB(+)CD123(- )DCs, but not normal synovial tissue sublining. Apart from higher expression of HLA-DR, the numbers and phenotypes of SF pDCs were similar to those of normal PB pDCs. While the APC function of PB pDCs was less efficient than that of PB myeloid DCs, RA SF pDCs efficiently activated resting allogeneic PB T cells, and high levels of IFN-γ, IL-10, and tumor necrosis factor α were produced in response to incubation of allogeneic T cells with either type of SF DCs. Thus, pDCs are recruited to RA synovial tissue and comprise an APC population distinct from the previously described nuclear RelB(+ )synovial DCs. pDCs may contribute significantly to the local inflammatory environment

Salt and Metal Tolerance Involves Formation of Guttation Droplets in Species of the Aspergillus versicolor Complex

Three strains of the Aspergillus versicolor complex were isolated from a salty marsh at a former uranium mining site in Thuringia, Germany. The strains from a metal-rich environment were not only highly salt tolerant (up to 20% NaCl), but at the same time could sustain elevated Cs and Sr (both up to 100 mM) concentrations as well as other (heavy) metals present in the environment. During growth experiments when screening for differential cell morphology, the occurrence of guttation droplets was observed, specifically when elevated Sr concentrations of 25 mM were present in the media. To analyze the potential of metal tolerance being promoted by these excretions, proteomics and metabolomics of guttation droplets were performed. Indeed, proteins involved in up-regulated metabolic activities as well as in stress responses were identified. The metabolome verified the presence of amino sugars, glucose homeostasis-regulating substances, abscisic acid and bioactive alkaloids, flavones and quinones

Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint

Introduction. Femoral and patellar cartilage defects with a defect size > 2.5 cm2 are a potential indication for an autologous chondrocyte implantation (ACI). However, the influence of the localization and the absolute and relative defect size on the clinical outcome has not yet been determined. The purpose of this study is to analyze the influence of the localization and the absolute and relative defect size on the clinical outcome after third-generation autologous chondrocyte implantation. Methods. A total of 50 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D). A match paired analysis was performed of 25 treated femoral and 25 treated patella defects with a follow-up of three years. MRI data was used to do the manual segmentation of the cartilage layer throughout the knee joint. The defect size was determined by taking the defect size measured in the MRI in relation to the whole cartilage area. The clinical outcome was measured by the IKDC score and VAS pre-operatively and after six, 12, 24, and 36 months post-operatively. Results. IKDC and VAS scores showed a significant improvement from the baseline in both groups. Femoral cartilage defects showed significantly superior clinical results in the analyzed scores compared to patellar defects. The femoral group improved IKDC from 33.9 (SD 18.1) pre-operatively to 71.5 (SD 17.4) after three years and the VAS from 6.9 (SD 2.9) pre-operatively to 2.4 (SD 2.5) after three years. In the patellar group, IKDC improved from 36.1 (SD 12.6) pre-operatively to 54.7 (SD 20.3) after three years and the VAS improved from 6.7 (SD 2.8) pre-operatively to 3.4 (SD 2.) after three years. Regarding the defect size, results showed that the same absolute defect size at med FC (4.8, range 2–15) and patella (4.6, range 2–12) has a significantly different share of the total cartilaginous size of the joint compartment (med FC: 6.7, range 1.2–13.9; pat: 18.9, range 4.0–47.0). However, there was no significant influence of the relative defect size on the clinical outcome in either patellar or femoral localization. Conclusion. Third-generation autologous chondrocyte implantation in ACI-treated femoral cartilage defects leads to a superior clinical outcome in a follow-up of three years compared with patellar defects. No significant influence of the defect size was found in either femoral or patellar cartilage defects