Adipocyte fatty acid-binding protein potentiates toxic lipids-induced endoplasmic reticulum stress via suppression of JAK2-dependent autophagy

Oral PresentationINTRODUCTION: Chronic inflammation is the key link between obesity and its related metabolic complications. Endoplasmic reticulum (ER) stress is the potent trigger of inflammation in obese adipose tissue but how ER stress in immune cells relates to inflammation is unclear. Adipocyte fatty acid–binding protein (A-FABP) regulates endotoxin-induced inflammation in macrophages by forming a positive feedback loop with c-Jun-N terminal kinase (JNK) which is the downstream regulator of ER stress. Defective autophagy is shown in obese liver which leads to insulin resistance and elevated ER stress. Here we investigate the role of A-FABP in association with autophagy in potentiating toxic lipids-induced ER stress in macrophages …published_or_final_versio

Adipocyte Fatty Acid Binding Protein Potentiates Toxic Lipids-Induced Endoplasmic Reticulum Stress in Macrophages via Inhibition of Janus Kinase 2-dependent Autophagy

Lipotoxicity is implicated in the pathogenesis of obesity-related inflammatory complications by promoting macrophage infiltration and activation. Endoplasmic reticulum (ER) stress and adipocyte fatty acid binding protein (A-FABP) play key roles in obesity and mediate inflammatory activity through similar signaling pathways. However, little is known about their interplay in lipid-induced inflammatory responses. Here, we showed that prolonged treatment of palmitic acid (PA) increased ER stress and expression of A-FABP, which was accompanied by reduced autophagic flux in macrophages. Over-expression of A-FABP impaired PA-induced autophagy associating with enhanced ER stress and pro-inflammatory cytokine production, while genetic ablation or pharmacological inhibition of A-FABP reversed the conditions. PA-induced expression of autophagy-related protein (Atg)7 was attenuated in A-FABP over-expressed macrophages, but was elevated in A-FABP-deficient macrophages. Mechanistically, A-FABP potentiated the effects of PA by inhibition of Janus Kinase (JAK)2 activity, thus diminished PA-induced Atg7 expression contributing to impaired autophagy and further augmentation of ER stress. These findings suggest that A-FABP acts as autophagy inhibitor to instigate toxic lipids-induced ER stress through inhibition of JAK2-dependent autophagy, which in turn triggers inflammatory responses in macrophages. A-FABP-JAK2 axis may represent an important pathological pathway contributing to obesity-related inflammatory diseases.published_or_final_versio

Use of Saliva for Early Dengue Diagnosis

The importance of laboratory diagnosis of dengue cannot be undermined. In recent years, many dengue diagnostic tools have become available for various stages of the disease, but the one limitation is that they require blood as a specimen for testing. In many incidences, phlebotomy in needle-phobic febrile individuals, especially children, can be challenging, and the tendency to forgo a dengue blood test is high. To circumvent this, we decided to work toward a saliva-based assay (antigen-capture anti-DENV IgA ELISA, ACA-ELISA) that has the necessary sensitivity and specificity to detect dengue early. Overall sensitivity of the ACA-ELISA, when tested on saliva collected from dengue-confirmed patients (EDEN study) at three time points, was 70% in the first 3 days after fever onset and 93% between 4 to 8 days after fever onset. In patients with secondary dengue infections, salivary IgA was detected on the first day of fever onset in all the dengue confirmed patients. This demonstrates the utility of saliva in the ACA-ELISA for early dengue diagnostics. This technique is easy to perform, cost effective, and is especially useful in dengue endemic countries

Diet and ovarian cancer risk: a case–control study in China

This case–control study, conducted in Zhejiang, China during 1999–2000, investigated whether dietary factors have an aetiological association with ovarian cancer. Cases were 254 patients with histologically confirmed epithelial ovary cancer. The 652 controls comprised 340 hospital visitors, 261 non-neoplasm hospital outpatients without long-term diet modifications and 51 women recruited from the community. A validated food frequency questionnaire was used to measure the habitual diet of cases and controls. The risks of ovarian cancer for the dietary factors were assessed by adjusted odds ratios based on multivariate logistic regression analysis, accounting for potential confounding demographic, lifestyle, familial factors and hormonal status, family ovarian cancer history and total energy intake. The ovarian cancer risk declined with increasing consumption of vegetables and fruits but vice versa with high intakes of animal fat and salted vegetables. The adjusted upper quartile odds ratio compared to the lower quartile was 0.24 (0.1–0.5) for vegetables, 0.36 (0.2–0.7) for fruits, 4.6 (2.2–9.3) for animal fat and 3.4 (2.0–5.8) for preserved (salted) vegetables with significant dose-response relationship. The risk of ovarian cancer also appeared to increase for those women preferring fat, fried, cured and smoked food

Dopamine Modulates Persistent Synaptic Activity and Enhances the Signal-to-Noise Ratio in the Prefrontal Cortex

The importance of dopamine (DA) for prefrontal cortical (PFC) cognitive functions is widely recognized, but its mechanisms of action remain controversial. DA is thought to increase signal gain in active networks according to an inverted U dose-response curve, and these effects may depend on both tonic and phasic release of DA from midbrain ventral tegmental area (VTA) neurons.We used patch-clamp recordings in organotypic co-cultures of the PFC, hippocampus and VTA to study DA modulation of spontaneous network activity in the form of Up-states and signals in the form of synchronous EPSP trains. These cultures possessed a tonic DA level and stimulation of the VTA evoked DA transients within the PFC. The addition of high (≥1 µM) concentrations of exogenous DA to the cultures reduced Up-states and diminished excitatory synaptic inputs (EPSPs) evoked during the Down-state. Increasing endogenous DA via bath application of cocaine also reduced Up-states. Lower concentrations of exogenous DA (0.1 µM) had no effect on the up-state itself, but they selectively increased the efficiency of a train of EPSPs to evoke spikes during the Up-state. When the background DA was eliminated by depleting DA with reserpine and alpha-methyl-p-tyrosine, or by preparing corticolimbic co-cultures without the VTA slice, Up-states could be enhanced by low concentrations (0.1–1 µM) of DA that had no effect in the VTA containing cultures. Finally, in spite of the concentration-dependent effects on Up-states, exogenous DA at all but the lowest concentrations increased intracellular current-pulse evoked firing in all cultures underlining the complexity of DA's effects in an active network.Taken together, these data show concentration-dependent effects of DA on global PFC network activity and they demonstrate a mechanism through which optimal levels of DA can modulate signal gain to support cognitive functioning

Risk groups defined by Recursive Partitioning Analysis of patients with colorectal adenocarcinoma treated with colorectal resection

<p>Abstract</p> <p>Background</p> <p>To define different prognostic groups of surgical colorectal adenocarcinoma patients derived from recursive partitioning analysis (RPA).</p> <p>Methods</p> <p>Ten thousand four hundred ninety four patients with colorectal adenocarcinoma underwent colorectal resection from Taiwan Cancer Database during 2003 to 2005 were included in this study. Exclusion criteria included those patients with stage IV disease or without number information of lymph nodes. For the definition of risk groups, the method of classification and regression tree was performed. Main primary outcome was 5-year cancer-specific survival.</p> <p>Results</p> <p>We identified six prognostic factors for cancer-specific survival, resulting in seven terminal nodes. Four risk groups were defined as following: Group 1 (mild risk, 1,698 patients), Group 2 (moderate risk, 3,129 patients), Group 3 (high risk, 4,605 patients) and Group 4 (very high risk, 1,062 patients). The 5-year cancer-specific survival for Group 1, 2, 3, and 4 was 86.6%, 62.7%, 55.9%, and 36.6%, respectively (p < 0.001). Hazard ratio of death was 2.13, 5.52 and 10.56 (95% confidence interval 1.74-2.60, 4.58-6.66 and 8.66-12.9, respectively) times for Group 2, 3, and 4 as compared to Group 1. The predictive capability of these grouping was also similar in terms of overall and progression-free survival.</p> <p>Conclusion</p> <p>The use of RPA offered an alternative grouping method that could predict the survival of patients who underwent surgery for colorectal adenocarcinoma.</p

Organizational commitment, knowledge sharing and organizational citizenship behaviour: the case of the Taiwanese semiconductor industry

[[abstract]]The semiconductor industry has made great contributions to Taiwan’s economy in the past 20 years. Because of competitive salaries and generous fringe benefits, some famous semiconductor manufacturers have become the best choice for students right after graduation. However, such magnetic effect has gradually faded away in the face of implementation of expensive employee bonuses. In a changeable environment, sharing knowledge will maintain organizational competitiveness and improve employees’ cohesion. As the semiconductor industry is characterized by a low-wage and high-turnover rate, the incurred job insecurities and career uncertainties have begun to force employees to change their cohesion, loyalty to organizations and even to reduce their willingness to share knowledge with others. This study aims to explore the relationships among organizational commitment (OC), knowledge sharing (KS) and organizational citizenship behavior (OCB) in the Taiwanese semiconductor industry. On the basis of 428 subjects, the results show that KS has a partial mediating effect on the OC–OCB relationship.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SSCI[[ispeerreviewed]]Y[[booktype]]紙本[[countrycodes]]GB

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Is quality of colorectal cancer care good enough? Core measures development and its application for comparing hospitals in Taiwan

<p>Abstract</p> <p>Background</p> <p>Although performance measurement for assessing care quality is an emerging area, a system for measuring the quality of cancer care at the hospital level has not been well developed. The purpose of this study was to develop organization-based core measures for colorectal cancer patient care and apply these measures to compare hospital performance.</p> <p>Methods</p> <p>The development of core measures for colorectal cancer has undergone three stages including a modified Delphi method. The study sample originated from 2004 data in the Taiwan Cancer Database, a national cancer data registry. Eighteen hospitals and 5585 newly diagnosed colorectal cancer patients were enrolled in this study. We used indicator-based and case-based approaches to examine adherences simultaneously.</p> <p>Results</p> <p>The final core measure set included seventeen indicators (1 pre-treatment, 11 treatment-related and 5 monitoring-related). There were data available for ten indicators. Indicator-based adherence possesses more meaningful application than case-based adherence for hospital comparisons. Mean adherence was 85.8% (79.8% to 91%) for indicator-based and 82.8% (77.6% to 88.9%) for case-based approaches. Hospitals performed well (>90%) for five out of eleven indicators. Still, the performance across hospitals varied for many indicators. The best and poorest system performance was reflected in indicators T5-negative surgical margin (99.3%, 97.2% - 100.0%) and T7-lymph nodes harvest more than twelve(62.7%, 27.6% - 92.2%), both of which related to surgical specimens.</p> <p>Conclusions</p> <p>In this nationwide study, quality of colorectal cancer care still shows room for improvement. These preliminary results indicate that core measures for cancer can be developed systematically and applied for internal quality improvement.</p