Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial

AbstractPurposeThe aim of this study was to investigate the efficacy and tolerability of GCSB-5, a mixture of 6 purified herbal extracts, in treating hand osteoarthritis (OA).MethodsA randomized, double-blind, placebo-controlled trial enrolled 220 patients with hand OA who had baseline a visual analog scale joint pain score of >30 of 100 mm at 3 hospitals between September 2013 and November 2014. After randomization, patients were allocated to receive oral GCSB-5 600 mg or placebo, bid for 12 weeks. The primary end point was the change in the Australian/Canadian OA Hand Index (AUSCAN)-defined pain score at 4 weeks relative to baseline. Secondary end points included the frequency Outcome Measures in Rheumatology–OA Research Society International (OMERACT-OARSI)-defined response at 4, 8, 12, and 16 weeks after randomization.FindingsThe allocated treatment was received by 109 and 106 patients in the GCSB-5 and placebo groups, respectively. At 4 weeks, the median (interquartile range) change in AUSCAN pain score relative to baseline was significantly greater in the GCSB-5 group than in the placebo group (–9.0 [–23.8 to –0.4] vs –2.2 [–16.7 to 6.0]; P = 0.014), with sustained improvement at 8, 12, and 16 weeks (P = 0.039). The GCSB-5 group also had a significantly greater OMERACT-OARSI–defined response rate than did the placebo group at 4 weeks (44.0% vs 30.2%), 8 weeks (51.4% vs 35.9%), 12 weeks (56.9% vs 40.6%), and 16 weeks (50.5% vs 37.7%) (P = 0.0074). The 2 treatments exhibited comparable safety profiles.ImplicationsGCSB-5 was associated with improved symptoms of hand OA, with good tolerability, in these patients. GCSB-5 may be a well-tolerated alternative of, or addition to, the treatment of hand OA. ClinicalTrials.gov identifier: NCT01910116

Ejaculatory Failure after Unilateral Neurolytic Celiac Plexus Block

Abdominal pain associated with chronic pancreatitis is often difficult to control with analgesics and can be severely debilitating with significant impairment of quality of life. In these patients, neurolytic celiac plexus block (NCPB) is an effective treatment option with a low complication rate. However, there is a risk of ejaculatory failure after NCPB, which may be a problem in patients with a long life expectancy. We report a case of ejaculatory failure after unilateral NCPB in a patient with chronic pancreatitis

Impact of Desensitization on Antiviral Immunity in HLA-Sensitized Kidney Transplant Recipients

Viral infections represent significant morbidity and mortality factors in kidney transplant recipients, with CMV, EBV, and BKV infections being most common. Desensitization (DES) with IVIg and rituximab with/without plasma exchange followed by kidney transplantation with alemtuzumab induction increased successful transplant rates in HLA-sensitized patients but may represent an increased risk for viral infections due to severe lymphocyte depletion. Here, we report on the posttransplant viral infection status in 372 DES versus 538 non-DES patients. CMV and EBV viremia were significantly lower in DES patients, while BKV viremia was similar. This trend was observed primarily in CMV sero(−), EBV sero(+), and sero(−) patients. No patient developed PTLD. The incidence of BKAN, allograft, and patient survival was similar in both groups. These viral infections were not associated with subsequent allograft rejection which occurred within 6 months after the infection. Conclusions. The IVIg + rituximab desensitization combined with alemtuzumab induction with triple immunosuppression maintenance does not increase the risk for CMV, EBV, and BKV infections. Possible factors include, in addition to posttransplant antiviral prophylaxis and PCR monitoring, presence of memory T cells and antibodies specific to CMV and likely EBV, NK cell-mediated ADCC despite lymphocyte depletion, elimination of EBV and CMV reservoirs by rituximab and alemtuzumab, and use of IVIg with antiviral properties

Comparison of Cytokine Expression in Mesenchymal Stem Cells from Human Placenta, Cord Blood, and Bone Marrow

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into lineages of mesenchymal tissues that are currently under investigation for a variety of therapeutic applications. The purpose of this study was to compare cytokine gene expression in MSCs from human placenta, cord blood (CB) and bone marrow (BM). The cytokine expression profiles of MSCs from BM, CB and placenta (amnion, decidua) were compared by proteome profiler array analysis. The cytokines that were expressed differently, in each type of MSC, were analyzed by real-time PCR. We evaluated 36 cytokines. Most types of MSCs had a common expression pattern including MIF (GIF, DER6), IL-8 (CXCL8), Serpin E1 (PAI-1), GROα(CXCL1), and IL-6. MCP-1, however, was expressed in both the MSCs from the BM and the amnion. sICAM-1 was expressed in both the amnion and decidua MSCs. SDF-1 was expressed only in the BM MSCs. Real-time PCR demonstrated the expression of the cytokines in each of the MSCs. The MSCs from bone marrow, placenta (amnion and decidua) and cord blood expressed the cytokines differently. These results suggest that cytokine induction and signal transduction are different in MSCs from different tissues

Acetic acid-indigo carmine chromoendoscopy for delineating early gastric cancers: its usefulness according to histological type

<p>Abstract</p> <p>Background</p> <p>Endoscopic treatments, such as endoscopic submucosal dissection (ESD) and laparoscopic gastrectomy, are increasingly used to treat a subset of patients with early gastric cancer (EGC). To achieve successful outcomes, it is very important to accurately determine the lateral extent of the tumor. Therefore, we investigated the diagnostic performance of chromoendoscopy using indigo carmine dye added to acetic acid (AI chromoendoscopy) in delineating differentiated or undifferentiated adenocarcinomas in patients with EGC.</p> <p>Methods</p> <p>We prospectively included 151 lesions of 141 patients that had an endoscopic diagnosis of EGC. All the lesions were examined by conventional endoscopy and AI chromoendoscopy before ESD or laparoscopic gastrectomy. The border clarification between the lesion and the normal mucosa was classified as distinct or indistinct before and after AI chromoendoscopy.</p> <p>Results</p> <p>The borders of the lesions were distinct in 66.9% (101/151) with conventional endoscopy and in 84.1% (127/151) with AI chromoendoscopy (<it>P </it>< 0.001). Compared with conventional endoscopy, AI chromoendoscopy clarified the border in a significantly higher percentage of differentiated adenocarcinomas (74/108 [68.5%] vs 97/108 [89.8%], respectively, <it>P </it>< 0.001). However, the border clarification rate for undifferentiated adenocarcinomas did not differ between conventional endoscopy and AI chromoendoscopy (27/43 [62.8%] vs 30/43 [70.0%], respectively, <it>P </it>= 0.494).</p> <p>Conclusions</p> <p>AI chromoendoscopy is useful in determining the lateral extent of EGCs. However, its usefulness is reduced in undifferentiated adenocarcinomas.</p

Toxoplasma gondii Infection in the Brain Inhibits Neuronal Degeneration and Learning and Memory Impairments in a Murine Model of Alzheimer's Disease

Immunosuppression is a characteristic feature of Toxoplasma gondii-infected murine hosts. The present study aimed to determine the effect of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of Alzheimer's disease (AD) in Tg2576 AD mice. Mice were infected with a cyst-forming strain (ME49) of T. gondii, and levels of inflammatory mediators (IFN-γ and nitric oxide), anti-inflammatory cytokines (IL-10 and TGF-β), neuronal damage, and β-amyloid plaque deposition were examined in brain tissues and/or in BV-2 microglial cells. In addition, behavioral tests, including the water maze and Y-maze tests, were performed on T. gondii-infected and uninfected Tg2576 mice. Results revealed that whereas the level of IFN-γ was unchanged, the levels of anti-inflammatory cytokines were significantly higher in T. gondii-infected mice than in uninfected mice, and in BV-2 cells treated with T. gondii lysate antigen. Furthermore, nitrite production from primary cultured brain microglial cells and BV-2 cells was reduced by the addition of T. gondii lysate antigen (TLA), and β-amyloid plaque deposition in the cortex and hippocampus of Tg2576 mouse brains was remarkably lower in T. gondii-infected AD mice than in uninfected controls. In addition, water maze and Y-maze test results revealed retarded cognitive capacities in uninfected mice as compared with infected mice. These findings demonstrate the favorable effects of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of AD in Tg2576 mice

Prevalence of Neuropathic Pain and Patient-Reported Outcomes in Korean Adults with Chronic Low Back Pain Resulting from Neuropathic Low Back Pain

Study DesignA noninterventional, multicenter, cross-sectional study.PurposeWe investigated the prevalence of neuropathic pain (NP) and patient-reported outcomes (PROs) of the quality of life (QoL) and functional disability in Korean adults with chronic low back pain (CLBP).Overview of LiteratureAmong patients with CLBP, 20%–55% had NP.MethodsPatients older than 20 years with CLBP lasting for longer than three months, with a visual analog scale (VAS) pain score higher than four, and with pain medications being used for at least four weeks before enrollment were recruited from 27 general hospitals between December 2014 and May 2015. Medical chart reviews were performed to collect demographic/clinical features and diagnosis of NP (douleur neuropathique 4, DN4). The QoL (EuroQoL 5-dimension, EQ-5D; EQ-VAS) and functional disability (Quebec Back Pain Disability Scale, QBPDS) were determined through patient surveys. Multiple linear regression analyses were performed to compare PROs between the NP (DN4≥4) and non-NP (DN4<4) groups.ResultsA total of 1,200 patients (females: 65.7%; mean age: 63.4±13.0 years) were enrolled. The mean scores of EQ-5D, EQ-VAS, and QBPDS were 0.5±0.3, 55.7±19.4, and 40.4±21.1, respectively. Among all patients, 492 (41.0%; 95% confidence interval, 38.2%–43.8%) suffered from NP. The prevalence of NP was higher in male patients (46.8%; p<0.01), in patients who had pain based on radiological and neurological findings (59.0%; p<0.01), and in patients who had severe pain (49.0%; p<0.01). There were significant mean differences in EQ-5D (NP group vs. non-NP group: 0.4±0.3 vs. 0.5±0.3; p<0.01) and QBPDS (NP group vs. non-NP group: 45.8±21.2 vs. 36.3±20.2; p<0.01) scores. In the multiple linear regression, patients with NP showed lower EQ-5D (β=−0.1; p<0.01) and higher QBPDS (β=7.0; p<0.01) scores than those without NP.ConclusionsNP was highly prevalent in Korean patients with CLBP. Patients with CLBP having NP had a lower QoL and more severe dysfunction than those without NP. To enhance the QoL and functional status of patients with CLBP, this study highlights the importance of appropriately diagnosing and treating NP

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe