Proteomic and biochemical analyses reveal the activation of unfolded protein response, ERK-1/2 and ribosomal protein S6 signaling in experimental autoimmune myocarditis rat model

<p>Abstract</p> <p>Background</p> <p>To investigate the molecular and cellular pathogenesis underlying myocarditis, we used an experimental autoimmune myocarditis (EAM)-induced heart failure rat model that represents T cell mediated postinflammatory heart disorders.</p> <p>Results</p> <p>By performing unbiased 2-dimensional electrophoresis of protein extracts from control rat heart tissues and EAM rat heart tissues, followed by nano-HPLC-ESI-QIT-MS, 67 proteins were identified from 71 spots that exhibited significantly altered expression levels. The majority of up-regulated proteins were confidently associated with unfolded protein responses (UPR), while the majority of down-regulated proteins were involved with the generation of precursor metabolites and energy metabolism in mitochondria. Although there was no difference in AKT signaling between EAM rat heart tissues and control rat heart tissues, the amounts and activities of extracellular signal-regulated kinase (ERK)-1/2 and ribosomal protein S6 (rpS6) were significantly increased. By comparing our data with the previously reported myocardial proteome of the Coxsackie viruses of group B (CVB)-mediated myocarditis model, we found that UPR-related proteins were commonly up-regulated in two murine myocarditis models. Even though only two out of 29 down-regulated proteins in EAM rat heart tissues were also dysregulated in CVB-infected rat heart tissues, other proteins known to be involved with the generation of precursor metabolites and energy metabolism in mitochondria were also dysregulated in CVB-mediated myocarditis rat heart tissues, suggesting that impairment of mitochondrial functions may be a common underlying mechanism of the two murine myocarditis models.</p> <p>Conclusions</p> <p>UPR, ERK-1/2 and S6RP signaling were activated in both EAM- and CVB-induced myocarditis murine models. Thus, the conserved components of signaling pathways in two murine models of acute myocarditis could be targets for developing new therapeutic drugs or methods aimed at treating enigmatic myocarditis.</p

Effective gauge group of pure loop quantum gravity is SO(3): New estimate of the Immirzi parameter

We argue that the effective gauge group for {\it pure} four-dimensional loop quantum gravity(LQG) is SO(3) (or $SO(3,C)$) instead of SU(2) (or $SL(2,C)$). As a result, links with half-integer spins in spin network states are not realized for {\it pure} LQG, implying a modification of the spectra of area and volume operators. Our observations imply a new value of $\gamma \approx 0.170$ for the Immirzi parameter which is obtained from matching the Bekenstein-Hawking entropy to the number of states from LQG calculations. Moreover, even if the dominant contribution to the entropy is not assumed to come from configurations with the minimum spins, the results of both pure LQG and the supersymmetric extension of LQG can be made compatible when only integer spins are realized for the former, while the latter also contains half-integer spins, together with an Immirzi parameter for the supersymmetric case which is twice the value of the SO(3) theory. We also verify that the $-{1/2}$ coefficient of logarithmic correction to the Bekenstein-Hawking entropy formula is robust, independent of whether only integer, or also half-integer spins, are realized.Comment: new value of Immirzi parameter is ~0.170; dominance of miminum spin configurations is not assumed in comparing with Bekenstein-Hawking formula; typos corrected. Version pressed in PL

A Multicentre Analysis Of Employment Post-Spinal Cord Injury In Malaysia

OBJECTIVES: Employment outcome post-spinal cord injury (SCI) varies internationally due to different socioeconomic backgrounds. However, most previous studies were done in developed countries, with limited studies from developing countries like Malaysia. This research aims to study the employment rate, positive determinants of employment, and reasons for unemployment post-SCI in Malaysia. DESIGN: We conducted a cross-sectional multicentre survey study in Malaysia. This study included eight hospitals with inpatient rehabilitation services and one SCI organisation throughout Malaysia. 280 SCI individuals from 18 to 64 years old with more than one year of SCI duration participated in this study. We administered International Spinal Cord Injury (InSCI) Questionnaires to them. We extracted and analysed the relevant components like demographics, injury-related and work-related data. We identified significant positive determinants of employment by using logistic regression analyses with p-value <0.05 between categorical independent variables and employment status. We described reasons for unemployment post-SCI in frequencies of percentages. RESULTS: The employment rate post-SCI in Malaysia was 29%. Significant positive determinants of employment post-SCI in Malaysia identified from logistic regression analyses with higher odds of employment were female gender (OR [Odds Ratio]: 2.2, 95%, CI [Confidence Interval]: 1.1-4.2); being married (OR: 1.9, CI:1.1-3.4); and tertiary education (OR: 3.2, CI: 1.6-6.8. The five main reasons for unemployment post-SCI in Malaysia were health condition or disability (36.5%), inability to find suitable work (15.5%), not knowing how or where to seek work (11.5%), lack of accessibility to potential workplace (7.4%), and insufficient transportation services (6.2%) CONCLUSION: This study reported a low employment rate post-SCI in Malaysia. Tertiary education was a strong positive determinant of employment. Based on this study ’ s findings, suggested interventions focus on access to tertiary education, health condition optimisation, vocational guidance, exploration of telework options, creating a barrier-free environment, and provision of sufficient transportation services can raise the employment rate post-SCI

Spinal epidural hematoma after epidural anesthesia in a patient receiving enoxaparin -A case report-

Spinal epidural hematoma is a rare but serious neurological complication of neuraxial anesthesia. Enoxaparin sodium is a low molecular weight heparin (LMWH) for use in preventing deep venous thrombosis in patients undergoing total hip arthroplasty and total knee arthroplasty. Hemorrhage is an uncommon but documented adverse reaction when using LMWH. We report a case of epidural hematoma after lumbar epidural anesthesia in a patient who administered enoxaparin in perioperative period

Bone and Cartilage Turnover Markers, Bone Mineral Density, and Radiographic Damage in Men with Ankylosing Spondylitis

PURPOSE: To determine the levels of bone and cartilage turnover markers in men with ankylosing spondylitis (AS) and to investigate their associations with disease activity, bone mineral density, and radiographic damage of the spine. PATIENTS AND METHODS: This cross-sectional study enrolled 35 men with newly diagnosed AS. The bone mineral densities (BMD) of their lumbar spines and proximal femurs, Bath AS Disease Activity Index (BASDAI), and Bath AS Radiographic Index (BASRI) were evaluated. Urinary C-terminal telopeptide fragments of type I collagen (CTX-I) and type II collagen (CTX-II) levels were determined by enzyme-linked immunosorbent assay, and serum levels of bone-specific alkaline phosphatase (BALP) and osteocalcin were determined by an enzyme immunoassay. Levels of biochemical markers were compared with those of 70 age-matched healthy men. RESULTS: Patients with AS had significantly higher mean urinary CTX-I and CTX-II levels than control subjects (p < 0.05). Elevated urinary CTX-I levels correlated well with BASDAI, femoral BMD, and femoral T score (p < 0.05), and elevated urinary CTX-II levels correlated well with spinal BASRI (p < 0.05) in patients with AS. Mean serum BALP and osteocalcin levels did not differ between patients and controls and did not show any significant correlations with BMD, BASDAI, or BASRI in men with AS. Conclusions: Elevated CTX-I reflects disease activity and loss of femoral BMD while elevated CTX-II levels correlate well with radiographic damage of the spine, suggesting the usefulness of these markers for monitoring disease activity, loss of BMD, and radiographic damage in men with AS.ope