Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC

Extracts of Feijoa Inhibit Toll-Like Receptor 2 Signaling and Activate Autophagy Implicating a Role in Dietary Control of IBD

Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory disease affecting the gut with limited treatment success for its sufferers. This suggests the need for better understanding of the different subtypes of the disease as well as nutritional interventions to compliment current treatments. In this study we assess the ability of a hydrophilic feijoa fraction (F3) to modulate autophagy a process known to regulate inflammation, via TLR2 using IBD cell lines

Updated meta-analysis of randomized controlled trials comparing conventional excisional haemorrhoidectomy with LigaSure for haemorrhoids

Background:\ud To compare the surgical outcome of haemorrhoidectomy performed using LigaSure bipolar diathermy with conventional haemorrhoidectomy.\ud \ud Methods:\ud Only randomized and alternate allocated studies were included from the major electronic databases using the search terms "ligasure" and "haemorrhoids" Duration of operation, blood loss during operation, postoperative pain score, wound healing, in-hospital stay, time to return to normal activities and complications were assessed.\ud \ud Results:\ud The 11 trials contained a total of 1,046 patients; the largest study was based on 273 patients and two earlier studies were based on 34 patients. No significant gender mismatch between the groups was reported in any of the studies. The patients’ ages were similar between groups in the studies, as was disease severity. All 11 studies reported a shorter duration of the operation when using LigaSure compared to the conventional technique (p<0.001). The postoperative pain score (p=0.001) and blood loss during operation (p=0.001) were significantly reduced. After LigaSure haemorrhoidectomy wound healing (p=0.004) and the return to normal activities (p=0.001) were significantly faster than after conventional haemorrhoidectomy. However, the overall incidence of complications reported was not significantly different (p=0.056).\ud \ud Conclusions:\ud LigaSure is an effective instrument for haemorrhoidectomy which results in less blood loss, quicker wound healing and earlier return to work.\u

Involvement of RhoA-mediated Ca(2+ )sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice

BACKGROUND: It has recently been suggested that RhoA plays an important role in the enhancement of the Ca(2+ )sensitization of smooth muscle contraction. In the present study, a participation of RhoA-mediated Ca(2+ )sensitization in the augmented bronchial smooth muscle (BSM) contraction in a murine model of allergic asthma was examined. METHODS: Ovalbumin (OA)-sensitized BALB/c mice were repeatedly challenged with aerosolized OA and sacrificed 24 hours after the last antigen challenge. The contractility and RhoA protein expression of BSMs were measured by organ-bath technique and immunoblotting, respectively. RESULTS: Repeated OA challenge to sensitized mice caused a BSM hyperresponsiveness to acetylcholine (ACh), but not to high K(+)-depolarization. In α-toxin-permeabilized BSMs, ACh induced a Ca(2+ )sensitization of contraction, which is sensitive to Clostridium botulinum C3 exoenzyme, indicating that RhoA is implicated in this Ca(2+ )sensitization. Interestingly, the ACh-induced, RhoA-mediated Ca(2+ )sensitization was significantly augmented in permeabilized BSMs of OA-challenged mice. Moreover, protein expression of RhoA was significantly increased in the hyperresponsive BSMs. CONCLUSION: These findings suggest that the augmentation of Ca(2+ )sensitizing effect, probably via an up-regulation of RhoA protein, might be involved in the enhanced BSM contraction in antigen-induced airway hyperresponsiveness

Influence of microRNA deregulation on chaperone-mediated autophagy and α-synuclein pathology in Parkinson's disease

The presence of α-synuclein aggregates in the characteristic Lewy body pathology seen in idiopathic Parkinson's disease (PD), together with α-synuclein gene mutations in familial PD, places α-synuclein at the center of PD pathogenesis. Decreased levels of the chaperone-mediated autophagy (CMA) proteins LAMP-2A and hsc70 in PD brain samples suggests compromised α-synuclein degradation by CMA may underpin the Lewy body pathology. Decreased CMA protein levels were not secondary to the various pathological changes associated with PD, including mitochondrial respiratory chain dysfunction, increased oxidative stress and proteasomal inhibition. However, decreased hsc70 and LAMP-2A protein levels in PD brains were associated with decreases in their respective mRNA levels. MicroRNA (miRNA) deregulation has been reported in PD brains and we have identified eight miRNAs predicted to regulate LAMP-2A or hsc70 expression that were reported to be increased in PD. Using a luciferase reporter assay in SH-SY5Y cells, four and three of these miRNAs significantly decreased luciferase activity expressed upstream of the lamp-2a and hsc70 3'UTR sequences respectively. We confirmed that transfection of these miRNAs also decreased endogenous LAMP-2A and hsc70 protein levels respectively and resulted in significant α-synuclein accumulation. The analysis of PD brains confirmed that six and two of these miRNAs were significantly increased in substantia nigra compacta and amygdala respectively. These data support the hypothesis that decreased CMA caused by miRNA-induced downregulation of CMA proteins plays an important role in the α-synuclein pathology associated with PD, and opens up a new avenue to investigate PD pathogenesis

Effects of columnar disorder on flux-lattice melting in high-temperature superconductors

The effect of columnar pins on the flux-lines melting transition in high-temperature superconductors is studied using Path Integral Monte Carlo simulations. We highlight the similarities and differences in the effects of columnar disorder on the melting transition in YBa$_2$Cu$_3$O$_{7-\delta}$ (YBCO) and the highly anisotropic Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ (BSCCO) at magnetic fields such that the mean separation between flux-lines is smaller than the penetration length. For pure systems, a first order transition from a flux-line solid to a liquid phase is seen as the temperature is increased. When adding columnar defects to the system, the transition temperature is not affected in both materials as long as the strength of an individual columnar defect (expressed as a flux-line defect interaction) is less than a certain threshold for a given density of randomly distributed columnar pins. This threshold strength is lower for YBCO than for BSCCO. For higher strengths the transition line is shifted for both materials towards higher temperatures, and the sharp jump in energy, characteristic of a first order transition, gives way to a smoother and gradual rise of the energy, characteristic of a second order transition. Also, when columnar defects are present, the vortex solid phase is replaced by a pinned Bose glass phase and this is manifested by a marked decrease in translational order and orientational order as measured by the appropriate structure factors. For BSCCO, we report an unusual rise of the translational order and the hexatic order just before the melting transition. No such rise is observed in YBCO.Comment: 32 pages, 13 figures, revte

Prevalence of internet addiction and gaming disorders in Southeast Asia: A meta-analysis.

This meta-analytic review aimed to examine the pooled prevalence rates of Internet addiction and gaming disorders in Southeast Asia. Several databases including PubMed, MEDLINE, PsycINFO, Web of Science, Embase, and Cochrane Central were searched and a total of 24 studies were included in this study. The selection of studies was conducted in accordance to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Two meta-analyses were conducted to examine data on Internet addiction and gaming disorders separately. A random-effects model was employed to derive the pooled prevalence rate. Mixed-effects meta-regression and subgroup analyses were performed to examine the moderators of the between-study heterogeneity. Publication bias was tested using the Egger's regression test and funnel plot. Only seven out of the 11 Southeast Asian countries were represented in the literature. All except for two of the included studies were cross-sectional in nature. The findings revealed a pooled prevalence rate of 20.0% (95% confidence interval: 14.5%-27.0%) and 10.1% (95% confidence interval: 7.3%-13.8%) for Internet addiction and gaming disorders respectively. Mean age and study population were significant moderators of the between-study heterogeneity in the prevalence rates of gaming disorders such that samples involving older participants showed higher prevalence rate than those involving younger individuals. Country of study was found to be significant moderator of the between-heterogeneity for both Internet addiction and gaming disorders, however the findings should be interpreted with caution due to the small and unbalanced sample sizes. There was no significant publication bias. Such epidemiology research should be extended to the Southeast Asian countries that have not been studied or are under-studied. Given that the prevalence rates appear to be higher in Southeast Asia than in other world regions, future research should also explore the factors behind these inter-regional differences. Further longitudinal studies should also be conducted to examine the trajectories of such disorders

Cumulative survival in early-onset unilateral and bilateral breast cancer: an analysis of 1907 Taiwanese women

As the epidemiological pattern of breast cancer in modernising Asian countries differs greatly from that in Western countries, it is worthwhile to investigate the long-term prognoses of unilateral and bilateral breast cancer in these nations. A retrospective cohort study composed of 1907 Taiwanese women was conducted to follow 1863 unilateral and 44 bilateral cases of breast cancer. Time-dependent Cox regression was used to assess the risk of breast cancer death by considering the time course of unilateral and bilateral tumour development. The 15-year survival rates were 68.37, 62.63, and 26.42% for unilateral, synchronous bilateral, and metachronous bilateral breast cancer, respectively. Differences among types were most apparent after 5 years of follow-up. After adjusting for significant prognostic factors, the risk of death for overall bilateral breast cancer was 2.50-fold greater (95% CI, 1.43–4.37) compared to unilateral breast cancer. The corresponding figures were 1.12-fold (95% CI, 0.42–3.02) and 6.11-fold (95% CI, 3.14–11.89) for synchronous and metachronous bilateral breast cancer, respectively. Taiwanese women, who are frequently diagnosed with breast cancer before 50 years of age, showed poorer survival for metachronous bilateral than for synchronous bilateral or unilateral breast cancer. Survival was markedly poorer compared to recent data from Sweden