α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases

Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation

Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250 μM) concentration-dependently inhibited lipopolysaccharide (LPS)-induced NO and IL-1β release in primary cultured microglia. However, ketamine (100 and 250 μM) did not significantly inhibit the LPS-induced TNF-α production in microglia, except at the higher concentration (500 μM). Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2) phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation

Intensity modulated radiotherapy for elderly bladder cancer patients

<p>Abstract</p> <p>Background</p> <p>To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer.</p> <p>Methods</p> <p>From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison.</p> <p>Results</p> <p>The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% <it>vs </it>.37.5%, respectively; the corresponding values for disease-free survival were 58.3% <it>vs</it>. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% <it>vs</it>. 83.3%, respectively; and for metastases-free survival, the values were 66.7% <it>vs</it>. 60.0%, respectively. The 2-year OS rates for T1, 2 <it>vs</it>. T3, 4 were 66.7% <it>vs</it>. 35.4%, respectively (<it>p </it>= 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, <it>p </it>= 0.004).</p> <p>Conclusion</p> <p>IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate.</p

Associations between child maltreatment, PTSD, and internet addiction among Taiwanese students

AbstractThis study examines (1) the associations between multiple types of child maltreatment and Internet addiction, and (2) the mediating effects of post-traumatic stress disorder (PTSD) on these associations. We collected data from a national proportionately stratified random sample of 6233 fourth-grade students in Taiwan in 2014. We conducted bivariate correlations and sets of multiple regression analyses to examine the associations between multiple types of maltreatment (5 types in total) and Internet addiction, and to identify the mediating role of PTSD. The results reveal that being male and experiencing abuse (psychological neglect, physical neglect, paternal physical violence, sexual violence) were associated with increased risk among children of developing PTSD and Internet addiction. Moreover, PTSD mediated the associations between multiple types of maltreatment (except maternal physical violence) and Internet addiction. This study demonstrates (1) the effects of multiple types of maltreatment on the PTSD and Internet addiction of children and (2) the importance of early prevention and intervention in addressing related public-health concerns

Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats

Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root), has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Treatment of puerarin (25 and 50 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia in rats. Administration of puerarin at 50 mg/kg, showed marked reduction in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions as well as the mRNA expression of tumor necrosis factor-α (TNF-α) in ischemic regions. These expressions were markedly inhibited by the treatment of puerarin (50 mg/kg). In addition, puerarin (10~50 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by formyl-Met-Leu-Phe. On the other hand, puerarin (20~500 μM) did not significantly inhibit the thiobarbituric acid-reactive substance reaction in rat brain homogenates. An electron spin resonance (ESR) method was conducted on the scavenging activity of puerarin on the free radicals formed. Puerarin (200 and 500 μM) did not reduce the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, puerarin treatment may represent a novel approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

<p>Abstract</p> <p>Background</p> <p>To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer.</p> <p>Methods</p> <p>Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m²intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0).</p> <p>Results</p> <p>The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully.</p> <p>Conclusion</p> <p>HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted.</p

Relationships between Parent-Reported Parenting, Child-Perceived Parenting, and Children’s Mental Health in Taiwanese Children

The current study examines the relationship between parents’ and children’s reports of parenting and their effects on children’s mental health symptoms. Six hundred and sixty-six parent-child dyads in Taiwan participated in this study. The parents and the children filled out the parenting questionnaires, and the children also reported their general mental health. The results demonstrated that parental-reported and child-perceived parenting were positively correlated, but parents tended to report lower scores on authoritarian parenting and higher scores on Chinese parenting than did their children. There were also significant gender differences: The mothers reported higher authoritative parenting than did the fathers; and the boys perceived higher authoritarian and Chinese-culture specific parenting than did the girls. Moreover, the Chinese parenting had a negative effect on children’s mental health outcomes. Finally, our results showed that children’s perception of parenting had a stronger effect on children’s mental health symptoms than did parental reports on parenting, urging future research to include the children’s report when investigating the effects of parenting on children’s mental health outcomes

Correcting Front-end RF Impedance Mismatch for 2.4GHz Wireless Long- Distance Data Transmission

ABSTRACT In order to increase the higher competition in lowpower wireless network communication market, a highperformance and low-cost product is necessary to distinguish the difference with others. Through integrating the system performance with suitable L-shape impedance-match circuit assisting with some network analyzer, this target with a 2.4 GHz radio-frequency (RF) product in long-distance data transportation seems to be promisingly implemented. In short-distance data transportation, the ideal outputlink transportation rate (~ max. 54 Mb/sec) is slightly influenced by impedance mismatch between power amplifier (PA) and antenna port. However, it is tremendously reduced at long-distance condition and the transportation rate is decreased to ~ 24 Mb/sec. Using the attenuator to attenuate the real input signal to -70dB to simulate the real signal transportation, the packet error rate (PER) is less than 10% at a physical sublayer service data unit (PSDU) length of 1000 bytes under the communication 802.11g spec. as the real transmission rate is 20 Mb/sec. If the impedance of the transmission line is shifted, the long-distance transportation rate will be reduced to, almost, 20 x 24 / 54 = 8.8 Mb/sec. The transportation performance is greatly deducted. With the delicate design and the feasible component arrangement, the impedance mismatch influencing the long-distance (~ 100 m) data transportation is overcome and reduced to the acceptable range. In this investigation using 3.3 V power supply, we observe that the selection of electronic components with miniaturization is also an art to reduce the radiation side-effect

Comparison of eight modern preoperative scoring systems for survival prediction in patients with extremity metastasis

BACKGROUND: Survival is an important factor to consider when clinicians make treatment decisions for patients with skeletal metastasis. Several preoperative scoring systems (PSSs) have been developed to aid in survival prediction. Although we previously validated the Skeletal Oncology Research Group Machine-learning Algorithm (SORG-MLA) in Taiwanese patients of Han Chinese descent, the performance of other existing PSSs remains largely unknown outside their respective development cohorts. We aim to determine which PSS performs best in this unique population and provide a direct comparison between these models. METHODS: We retrospectively included 356 patients undergoing surgical treatment for extremity metastasis at a tertiary center in Taiwan to validate and compare eight PSSs. Discrimination (c-index), decision curve (DCA), calibration (ratio of observed:expected survivors), and overall performance (Brier score) analyses were conducted to evaluate these models' performance in our cohort. RESULTS: The discriminatory ability of all PSSs declined in our Taiwanese cohort compared with their Western validations. SORG-MLA is the only PSS that still demonstrated excellent discrimination (c-indexes>0.8) in our patients. SORG-MLA also brought the most net benefit across a wide range of risk probabilities on DCA with its 3-month and 12-month survival predictions. CONCLUSIONS: Clinicians should consider potential ethnogeographic variations of a PSS's performance when applying it onto their specific patient populations. Further international validation studies are needed to ensure that existing PSSs are generalizable and can be integrated into the shared treatment decision-making process. As cancer treatment keeps advancing, researchers developing a new prediction model or refining an existing one could potentially improve their algorithm's performance by using data gathered from more recent patients that are reflective of the current state of cancer care