Novel requirements for HAP2-mediated gamete fusion in Tetrahymena.

The ancestral gamete fusion protein, HAP2, catalyzes sperm-egg fusion in a broad range of taxa dating to the last eukaryotic common ancestor. Remarkably, HAP2 orthologs are structurally related to the class II fusogens of modern-day viruses, and recent studies make clear that these proteins utilize similar mechanisms to achieve membrane merger. To identify factors that may regulate HAP2 activity, we screened mutants of the ciliate Tetrahymena thermophila for behaviors that mimic Δhap2 knockout phenotypes in this species. Using this approach, we identified two new genes, GFU1 and GFU2, whose products are necessary for the formation of membrane pores during fertilization and show that the product of a third gene, namely ZFR1, may be involved in pore maintenance and/or expansion. Finally, we propose a model that explains cooperativity between the fusion machinery on apposed membranes of mating cells and accounts for successful fertilization in T. thermophila's multiple mating type system.

A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers.

BACKGROUND: YH4808, a K+ -competitive acid blocker, is under clinical development for the treatment of acid-related disorders, such as gastroesophageal reflux disease. AIMS: To determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole. METHODS: This double-blind, randomised, placebo- and active comparator (esomeprazole)-controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30-800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24-hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24). RESULTS: Plasma YH4808 exposure increased dose-proportionally and declined in a multi-phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24-hour period, respectively; and >50% vs 33% of a 9-hour night respectively). A twice-daily regimen of YH4808 more effectively controlled intragastric pH at night than a once-daily regimen. In evaluating the mean areas under the intragastric pH-time curves in 15-minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well-tolerated at all doses administered. CONCLUSION: This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid-related diseases.

The impact of obesity on febrile urinary tract infection and renal scarring in children with vesicoureteral reflux.

INTRODUCTION: It has become clear that obesity is associated with a variety of infectious diseases, including urinary tract infection (UTI) and renal scarring. OBJECTIVE: The aim of this study was to evaluate the association between obesity and the degree of febrile UTI (fUTI) and renal scarring in children with vesicoureteral reflux (VUR), and to stratify the results into obesity subcategories. STUDY DESIGN: A total of 186 patients were diagnosed with VUR between January 2002 and December 2008. This study retrospectively reviewed the medical records of 72 children with primary VUR who had recurrent fUTI (more than twice). Overweight or obese status of the patients aged <2 years was defined using weight-for-length (WFL) measurements. For 2-5 year old children, body mass index (BMI) percentile-for-age was used. They were divided into three groups as follows; standard (<85%), overweight (85-95%), and obese (≥95%). The following clinical variables were compared: age at diagnosis of primary VUR (months), sex, VUR grade, hydronephrosis grade, presence of renal scarring, surgical treatment, and degree of inflammation during fUTI. RESULTS: In the overweight and obese groups, VUR was diagnosed at a young age (P = 0.05), the degree of renal scarring was more severe (P = 0.006), and serum white blood cell count, C-reactive protein, and erythrocyte sedimentation rate (ESR) levels were significantly higher (P < 0.001, P < 0.001, and P < 0.001, respectively). Abnormal focal dimercaptosuccinic acid (DMSA) defects were present in 25 of the 72 children (35%). Cortical defects occurred more frequently in children with obesity, and they were associated with a higher grade of reflux and serum ESR levels (P = 0.007, P = 0.042, and P = 0.021, respectively). Among these risk factors, high-grade VUR (OR = 9.93, 95% CI = 1.13-86.71), and being overweight and obese (OR = 5.26, 95% CI = 1.75-15.82) were associated with increased renal scarring. However, ESR was not associated with renal scarring (OR = 1.01, 95% CI = 0.95-1.07). DISCUSSION: The relationships between obesity and UTI are controversial. Some studies have shown positive results; however, other studies have shown opposite results. The main limitations of this study were the retrospective data collection via electronic medical records, and the small number of subjects. CONCLUSIONS: This study showed that obesity in patients with VUR has an effect on fUTI and renal scar formation. If the patients with VUR have obesity, close follow-up should be performed, and VUR patients should be started on a weight-loss program, which could reduce the number of patients with chronic kidney disease in the future.

Differentiation of Hemangioblastoma from Metastatic Brain Tumor using Dynamic Contrast-enhanced MR Imaging.

PURPOSE: The aim of this study was to differentiate hemangioblastomas from metastatic brain tumors using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and compare the diagnostic performances with diffusion-weighted imaging (DWI) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). METHODS: We retrospectively reviewed 7 patients with hemangioblastoma and 15 patients with metastatic adenocarcinoma with magnetic resonance imaging (MRI) including DWI, DSC-MRI, and DCE-MRI. Apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), and DCE-MRI parameters (K trans, k ep, v e, and v p) were compared between the two groups. The diagnostic performance of each parameter was evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: v p, k ep, and rCBV were significantly different between patients with hemangioblastoma and those with metastatic brain tumor (p < 0.001, p = 0.005, and p = 0.017, respectively). A v p cutoff value of 0.012 and a rCBV cutoff value of 8.0 showed the highest accuracy for differentiating hemangioblastoma from metastasis. The area under the ROC curve for v p and rCBV was 0.99 and 0.89, respectively. A v p > 0.012 showed 100 % sensitivity, 93.3 % specificity, and 95.5 % accuracy and a rCBV > 8.0 showed 85.7 % sensitivity, 93.3 % specificity, and 90.9 % accuracy for differentiating hemangioblastoma from metastatic brain tumor. CONCLUSION: DCE-MRI was useful for differentiating hemangioblastoma from metastatic brain tumor.

Temperament and character traits in patients with tinnitus: a prospective case series with comparisons.

OBJECTIVE: To describe the personality traits of temperament and character in patients with tinnitus and to identify differences in these traits associated with the severity of tinnitus. STUDY DESIGN: Case series with comparisons. SETTING: Tertiary referral centre. PARTICIPANTS: From January to December 2014, one hundred and thirty-four adult patients with chronic subjective tinnitus completed psychoacoustic measurements of tinnitus and the Temperament and Character Inventory (TCI). MEASUREMENTS: Personality traits were assessed by the TCI. The TCI assesses seven dimensions of personality traits and four temperaments 'novelty seeking, harm avoidance, reward dependence, persistence', as well as three characters 'self-directedness, cooperativeness, self-transcendence'. MAIN OUTCOME MEASURES: The values of the TCI parameters in the tinnitus patients were compared with reference data from a non-institutional adult population, and associations between TCI parameter values and tinnitus severity were evaluated. RESULTS: In terms of temperament, tinnitus patients had higher scores for 'harm avoidance', whereas scores for 'novelty seeking', 'reward dependence' and 'persistence' were significantly lower than the reference. In terms of character, lower 'cooperativeness' and 'self-transcendence' were identified in the subjects with tinnitus. The 'novelty seeking' score was inversely related to tinnitus severity (r = -0.285, P = 0.001), while other temperament and character traits did not show significant correlations. CONCLUSIONS: There may be a connection between tinnitus and personality traits, especially in the case of 'novelty seeking', which is relatively constant over a lifetime. The TCI questionnaire may be useful in facilitating the application of personality traits to tailored counselling for tinnitus.

Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta.

BACKGROUND: Epigenetics is tissue-specific and potentially even cell-specific, but little information is available from human reproductive studies about the concordance of DNA methylation patterns in cord blood and placenta, as well as within-placenta variations. We evaluated methylation levels at promoter regions of candidate genes in biological ageing pathways (SIRT1, TP53, PPARG, PPARGC1A, and TFAM), a subtelomeric region (D4Z4) and the mitochondrial genome (MT-RNR1, D-loop). METHODS: Ninety individuals were randomly chosen from the ENVIRONAGE birth cohort to evaluate methylation concordance between cord blood and placenta using highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen individuals, a more extensive sampling scheme was performed to examine within-placenta variation. RESULTS: The DNA methylation levels of the subtelomeric region and mitochondrial genome showed concordance between cord blood and placenta with correlation coefficients ranging from r = 0.31 to 0.43, p ≤ 0.005, and also between the maternal and foetal sides of placental tissue (r = 0.53 to 0.72, p ≤ 0.05). For the majority of targets, an agreement in methylation levels between four foetal biopsies was found (with intra-class correlation coefficients ranging from 0.16 to 0.72), indicating small within-placenta variation. CONCLUSIONS: The methylation levels of the subtelomeric region (D4Z4) and mitochondrial genome (MT-RNR1, D-loop) showed concordance between cord blood and placenta, suggesting a common epigenetic signature of these targets between tissues. Concordance was lacking between the other genes that were studied. In placental tissue, methylation patterns of most targets on the mitochondrial-telomere axis were not strongly influenced by sample location.

Differential identification of three species of Curtovirus using loop-mediated isothermal amplification.

Rapid and sensitive detection methods for three species of Curtovirus were developed using a loop-mediated isothermal amplification (LAMP) technique. A universal primer set for detecting the three main species of Curtovirus at the same time, and three kinds of species-specific primer sets were designed and used for LAMP reactions. Results from the LAMP reactions were visualized both by color changes after adding SYBR Green I staining dye and by DNA laddering on agarose gel electrophoresis. The optimal conditions for the curtovirus LAMP reaction were confirmed at 60°C for the universal primers and at 62°C for the three species-specific primer sets. Amplification of curtoviruses by LAMP reaction was ten-fold more sensitive than that by polymerase chain reaction. Primers designed for curtovirus detection in this study did not anneal to or amplify DNA from other DNA or RNA viruses (tomato yellow leaf curl virus, tomato spotted wilt virus, and potato virus Y). Taken together, the primer sets and reaction conditions developed in this study show that the LAMP technique could be a useful tool to detect the three species of Curtovirus simultaneously and distinguish them in the laboratory and the field.

PKCδ phosphorylation is an upstream event of GSK3 inactivation-mediated ROS generation in TGF-ß1-induced senescence.

Transforming growth factor ß1 (TGF-ß1) induces Mv1Lu cell senescence through inactivating glycogen synthase kinase 3 (GSK3), thereby inactivating complex IV and increasing intracellular ROS. In the present study, we identified protein kinase C delta (PKCδ) as an upstream regulator of GSK3 inactivation in this mechanism of TGF-ß1-induced senescence. When Mv1Lu cells were exposed to TGF-ß1, PKCδ phosphorylation simultaneously increased with GSK3 phosphorylation, and then AKT and ERK were phosphorylated. AKT phosphorylation and Smad signaling were independent of GSK3 phosphorylation, but ERK phosphorylation was downstream of GSK3 inactivation. TGF-ß1-triggered GSK3 phosphorylation was blocked by inhibition of PKCδ, using its pharmacological inhibitor, Rottlerin, or overexpression of a dominant negative PKCδ mutant, but GSK3 inhibition with SB415286 did not alter PKCδ phosphorylation. Activation of PKCδ by PMA delayed cell growth and increased intracellular ROS level, but did not induce senescent phenotypes. In addition, overexpression of wild type or a constitutively active PKCδ mutant was enough to delay cell growth and decrease the mitochondrial oxygen consumption rate and complex IV activity, but weakly induce senescence. However, PMA treatment on Mv1Lu cells, which overexpress wild type and constitutively active PKCδ mutants, effectively induced senescence. These results indicate that PKCδ plays a key role in TGF-ß1-induced senescence of Mv1Lu cells through the phosphorylation of GSK3, thereby triggering mitochondrial complex IV dysfunction and intracellular ROS generation.

Thromboembolic complications in patients with clopidogrel resistance after coil embolization for unruptured intracranial aneurysms.

BACKGROUND AND PURPOSE: Antiplatelet resistance is known to be associated with symptomatic ischemic complication after endovascular coil embolization. The purpose of our study was to evaluate the relationship between antiplatelet resistance and clinically silent thromboembolic complications using DWI in patients who underwent coil embolization for unruptured intracranial aneurysm. MATERIALS AND METHODS: Between October 2011 and May 2013, 58 patients with 62 unruptured aneurysms who were measured for antiplatelet response using VerifyNow assay and underwent elective coil embolization for an unruptured aneurysm with posttreatment DWI were enrolled. Diffusion-positive lesions were classified into 3 groups according to the number of lesions (n=0 [grade 0], n<6 [grade I], and n≥6 [grade II]). The relationship between antiplatelet resistance and diffusion-positive lesions was analyzed. RESULTS: Sixty-two endovascular coiling procedures were performed on 58 patients. Clopidogrel resistance was revealed in 23 patients (39.7%) and diffusion-positive lesions were demonstrated in 28 patients (48.3%); these consisted of 19 (32.8%) grade I and 9 (15.5%) grade II lesions. Clopidogrel resistance was not relevant to the development of any diffusion-positive lesion (grade I and II, P=.789) but was associated with the development of multiple diffusion-positive lesions (grade II, P=.002). In the logistic regression prediction model, clopidogrel resistance showed significant correlation with the development of grade II lesions (P=.001). CONCLUSIONS: Multiple diffusion-positive lesions (≥6 in number) occurred more frequently in patients with clopidogrel resistance after endovascular coiling for unruptured aneurysms.

Diffusion and perfusion MRI findings of the signal-intensity abnormalities of brain associated with developmental venous anomaly.

BACKGROUND AND PURPOSE: Developmental venous anomalies are the most common intracranial vascular malformation. Increased signal-intensity on T2-FLAIR images in the areas drained by developmental venous anomalies are encountered occasionally on brain imaging studies. We evaluated diffusion and perfusion MR imaging findings of the abnormally high signal intensity associated with developmental venous anomalies to describe their pathophysiologic nature. MATERIALS AND METHODS: We retrospectively reviewed imaging findings of 34 subjects with signal-intensity abnormalities associated with developmental venous anomalies. All subjects underwent brain MR imaging with contrast and diffusion and perfusion MR imaging. Regions of interest were placed covering abnormally high signal intensity around developmental venous anomalies on fluid-attenuated inversion recovery imaging, and the same ROIs were drawn on the corresponding sections of the diffusion and perfusion MR imaging. We measured the apparent diffusion coefficient, relative cerebral blood volume, relative mean transit time, and time-to-peak of the signal-intensity abnormalities around developmental venous anomalies and compared them with the contralateral normal white matter. The Mann-Whitney U test was used for statistical analysis. RESULTS: The means of ADC, relative cerebral blood volume, relative mean transit time, and TTP of signal-intensity abnormalities around developmental venous anomalies were calculated as follows: 0.98 ± 0.13 10(-3)mm(2)/s, 195.67 ± 102.18 mL/100 g, 16.74 ± 7.38 seconds, and 11.65 ± 7.49 seconds, respectively. The values of normal WM were as follows: 0.74 ± 0.08 10(-3)mm(2)/s for ADC, 48.53 ± 22.85 mL/100 g for relative cerebral blood volume, 12.12 ± 4.27 seconds for relative mean transit time, and 8.35 ± 3.89 seconds for TTP. All values of ADC, relative cerebral blood volume, relative mean transit time, and TTP in the signal-intensity abnormalities around developmental venous anomalies were statistically higher than those of normal WM (All P < .001, respectively). CONCLUSIONS: The diffusion and perfusion MR imaging findings of the signal-intensity abnormalities associated with developmental venous anomaly suggest that the nature of the lesion is vasogenic edema with congestion and delayed perfusion.

First Report of Chickpea chlorotic dwarf virus Infecting Hot Pepper in India.

Hot pepper (Capsicum annuum) cultivated in India has been identified as a host of geminiviruses causing leaf curl disease such as Chilli leaf curl virus and Pepper leaf curl virus, leading to serious crop losses (3). In June 2013, hot pepper plants growing in Bangalore showed stunting and upward leaf curling. Viral DNA was extracted from a hot pepper with a Viral Gene-spin Viral DNA/RNA Extraction Kit (iNtRON Biotechnology, Seongnam, Korea) and amplified by rolling circle amplification using the illustra TempliPhi 100 Amplification Kit (GE Healthcare, Uppsala, Sweden) (2). Amplified products were digested by restriction enzyme KpnI (Takara Bio, Shiga, Japan), cloned, and sequenced (Macrogen, Seoul, Korea). Based on a BLAST search, a 2.6-kb DNA obtained from one plant sample was identified as Chickpea chlorotic dwarf virus (CpCDV), belonging to the genus Mastrevirus (family Geminiviridae) (GenBank Accession No. KF632712). The CpCDV-Bangalore isolate is 2,585 bases in length and exhibits 85.9 to 98.5% identity to previously reported CpCDV isolates. To our knowledge, this is the first report of CpCDV infecting hot pepper in India. CpCDV was recently reported from pepper plants in Oman (KF111683) (1), but it shared the lowest sequence identity (85.9%) with CpCDV-Bangalore isolate. References: (1) S. Akhtar et al. Plant Dis. 98:286, 2014. (2) E.-J. Kil et al. Arch. Virol. 159:2387. (3) D. M. J. B. Senanayake et al. Plant Pathol. 56:343, 2007.

First Report of Tomato yellow leaf curl virus Infecting Eustoma (Eustoma grandiflorum) in Korea.

Eustoma (Eustoma grandiflorum), also called lisianthus, belongs to the family Gentianaceae and is cultivated for flower production globally (1), including in Korea. At least 10 viruses can infect eustoma, including Cucumber mosaic virus (genus Cucumovirus), Tobacco mosaic virus (genus Tobamovirus), Tomato spotted wilt virus (genus Tospovirus), and Tomato yellow leaf curl virus (TYLCV, genus Begomovirus) (1,2). In December 2012, disease symptoms such as leaf curling and stunting were observed on eustoma plants grown in Gumi, Korea, where TYLCV outbreak was reported on tomato farms. In a eustoma greenhouse, about 5% of eustoma plants showed the leaf curling and stunting symptoms. Total DNA was isolated from 15 symptomatic eustoma plants with a Viral Gene-spin Viral DNA/RNA Extraction Kit (iNtRON Biotechnology, Seongnam, Korea) and viral DNA was amplified by rolling circle amplification (TempliPhi Amplification Kit, GE Healthcare Life Sciences, Uppsala, Sweden) following the manufacturer's instructions. All amplicons were digested with the restriction enzyme SacI (TaKaRa Bio, Shiga, Japan) and 2.8-kb DNA fragments were verified on an agarose gel. Fifteen digested DNA fragments were purified from the gel, ligated into pGEM-T easy vector (Promega, Madison, WI), and sequenced (Macrogen, Seoul, Korea, GenBank Accession No. KF225312.1). A BLAST search exhibited a 99% identity to TYLCV previously reported in Korea (GenBank HM856911.1). This is the first report of TYLCV in eustoma plants in Korea. To identify the movement and replication of TYLCV in infected eustoma plants, PCR and Southern hybridization analysis were performed with samples from four organs (flower, leaf, stem, and root) of three individual TYLCV-infected plants. TYLCV TYL DNA from each organ sample was amplified using 2× Taq PCR MasterMix (Bioneer, Daejeon, Korea) with TYLCV-specific primers (TYLCV-F: 5'-ATATTACCGGATGGCCGCGCCT-3', CV-R: 5'-TCCACGGGGAACATCAGGGCTT-3'). Single-stranded as well as double-stranded TYLCV DNA were identified from all organs of symptomatic eustoma, indicating TYLCV can replicate and move systemically in eustoma plants. Whitefly (Bemisia tabaci)-mediated plant-to-plant viral transmission was performed with one TYLCV-infected eustoma plant and five healthy eustoma plants and revealed that 80% (4 of 5) of the eustoma plants were infected by whitefly-mediated transmission. These results indicate that TYLCV-infected eustoma plants could act as virus reservoirs to healthy eustoma plants as well as other potential TYLCV hosts, such as tomatoes. In Korea, TYLCV has been the most notorious plant virus since 2008 (3), but, until now, TYLCV infection in eustoma plants has not been reported in Korea. References: (1) C. C. Chen et al. Plant Dis. 84:506, 2000. (2) A. Kritzman et al. Plant Dis. 84:1185, 2000. (3) H. Lee et al. Mol. Cells 30:467, 2010.

First Report of Sweet potato golden vein associated virus Infecting Sweet Potato in Korea.

Sweet potato (Ipomoea batatas) is one of the most important crops in eastern Asia, including Korea. Consumption of sweet potato is increasing gradually because of its growing reputation as a health food. Recently, outbreaks of viruses infecting sweet potatoes have increased all over the world, probably because sweet potatoes are produced via vegetative propagation (1,2). In Korea, most sweet potatoes in fields have been infected by a begomovirus, Sweet potato leaf curl virus (SPLCV), and other viruses such as Sweet potato feathery mottle virus, Sweet potato virus G, and Sweet potato latent virus (3). Many countries have monitored sweet potato virus infections in fields as well as in germplasm collections to select virus-free stocks. In 2013, 20 sweet potato plants showing leaf roll symptoms in Muan, South Korea, were collected and analyzed. Total DNA was isolated from sweet potato leaves (Viral Gene-spin Viral DNA/RNA Extraction Kit, iNtRON Biotechnology, Seongnam, Korea) and viral DNA was amplified by rolling circle amplification (RCA, TempliPhi Amplification Kit, GE Healthcare Life Sciences, Uppsala, Sweden) following the manufacturer's instructions. Amplicons were digested by restriction enzyme SacI (TaKaRa Bio, Shiga, Japan) and products were run on a 1.5% agarose gel. A 2.8-kb DNA fragment was purified from a gel, ligated into a pGEM-T easy vector (Promega, Madison, WI), and sequenced (Macrogen, Seoul, Korea). Based on a BLAST search, most of the sequences (36/38) were identified as SPLCV, but two independent clones 2,824 nt in length from sweet potato cv. Sincheonmi were similar to Sweet potato golden vein associated virus (SPGVaV) isolate US:MS:1B-3 (94.38%, GenBank Accession No. HQ333143). The complete genome sequence of the SPGVaV-Korea isolate contained six ORFs, as expected for a typical monopartite begomovirus. The sequence was deposited in GenBank under accession number KF803170. SPGVaV is a whitefly (Bemisia tabaci)-transmitted virus (genus Begomovirus, family Geminiviridae). A phylogenetic analysis that included other begomoviruses that infect sweet potato showed SPGVaV-Korea to segregate with other SPGVaV isolates. SPGVaV has previously only been reported in Brazil and the United States (1). This is the first report of SPGVaV in sweet potato outside of the Americas. References: (1) L. C. Albuquerque et al. Virol. J. 9:241, 2012. (2) E. Choi et al. Acta Virol. 56:187, 2012. (3) H. R. Kwak et al. Plant Pathol. J. 22:239, 2006.

Daily skin care habits and the risk of skin eruptions and symptoms in cancer patients.

BACKGROUND: Cancer patients are at high risk for skin problems because rapidly proliferating skin cells are susceptible to anticancer therapies. However, the effects of daily skin care habits on development of skin problems in cancer patients have rarely been studied. PATIENTS AND METHODS: We conducted a survey of daily skin care habits and the presence of skin problems in 866 cancer patients. RESULTS: Hot water bath>1 h significantly increased the risk of definite eruptions [odds ratio (OR) 4.09] and the risk of itching or pain on the skin (OR 1.73). Diligent use of moisturizers did not decrease the risk of definite eruptions and symptoms, and daily bathing, scrubbing off the skin while bathing, and sun protection did not influence the risk of definite eruptions and symptoms. Subgroup analysis of 183 breast cancer patients showed results similar to the total results, including that hot water bath>1 h significantly increased the risk of definite eruptions (OR 3.41). CONCLUSIONS: Being a cross-sectional study, our study could not prove causality. However, at the present stage of knowledge, avoidance of hot water baths of protracted duration should be first emphasized in patient education to prevent skin problems in cancer patients.

Posterior glottic gap and age as factors predicting voice outcome of injection laryngoplasty in patients with unilateral vocal fold paralysis.

OBJECTIVES: This study aimed to analyse demographic profiles and pre-injection stroboscopic findings for patients with unilateral vocal fold paralysis, to investigate possible predictive factors for voice outcomes of injection laryngoplasty. MATERIALS AND METHODS: Fifty-nine unilateral vocal fold paralysis patients underwent vocal fold augmentation, using transcutaneous Artecoll (polymethyl methacrylate microspheres plus bovine collagen) injection into the paralysed vocal fold via the cricothyroid space. Three months later, patients were divided into improved (n = 44) and unimproved (n = 15) groups, using the perceptual grade-roughness-breathiness-asthenia-strain scale, and their clinical characteristics and pre-operative stroboscopic findings compared. RESULTS: The improved group were significantly younger than the unimproved group (p = 0.000). The size of the posterior gap on phonation was closely associated with the outcome of injection laryngoplasty (p = 0.015). CONCLUSION: Younger patients with a smaller posterior glottic gap on phonation can be expected to have a more favourable outcome following injection laryngoplasty for correction of glottic insufficiency due to unilateral vocal fold paralysis.

Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress TNF-induced JNK activation.

The zinc-finger protein A20 has crucial physiological functions as a dual inhibitor of nuclear factor-κB (NF-κB) activation and apoptosis in tumor necrosis factor (TNF) receptor 1 signaling pathway. Although the molecular basis for the anti-NF-κB function of A20 has been well elucidated, the anti-apoptotic function of A20 is largely unknown. Here, we report a novel mechanism underlying the anti-apoptotic function of A20: A20 blocks TNF-induced apoptosis through suppression of c-jun N-terminal kinase (JNK) by targeting apoptosis signal-regulating kinase1 (ASK1). First, the ectopic expression of A20 drastically inhibits TNF-induced JNK activation and apoptosis in multiple cell types including those deficient of NF-κB activation. Unexpectedly, the blunting effect of A20 on TNF-induced JNK activation is not mediated by affecting the TNFR1 signaling complex formation. Instead, A20 interacts with ASK1, an important MAPKK kinase in the JNK signaling cascade. More importantly, overexpression of wild-type A20, but not of mutant A20 (ZnF4; C624A, C627A), promotes degradation of the ASK1 through the ubiquitin-proteasome system. Taken together, the results from this study reveal a novel anti-apoptotic mechanism of A20 in TNF signaling pathway: A20 binds to ASK1 and mediates ASK1 degradation, leading to suppression of JNK activation and eventually blockage of apoptosis.

Interleukin-6 small interfering RNA improved the herpes simplex virus-induced systemic inflammation in vivo Behcet's disease-like mouse model.

It is known that the level of interleukin-6 (IL-6) is higher in patients with active Behcet's disease (BD) than in those with inactive disease. Herpes simplex virus (HSV) type 1 inoculation of the earlobes of ICR mice resulted in the development of BD-like symptoms. To find out whether downregulation of IL-6 would affect the symptoms of BD, IL-6 small interfering RNA (siRNA) was administered to a BD mouse model. IL-6 siRNA was intraperitoneally injected into BD mice to downregulate IL-6 (n=9). IL-6 siRNA injection downregulated serum IL-6 level (118.9+/-114.4 pg ml(-1)) compared with scramble injection (439.4+/-378.0 pg ml(-1)) in BD mice (P=0.01). In seven out of nine IL-6 siRNA-injected BD mice, 77.8% improved and the severity score was decreased from 3.1+/-1.05 to 1.7+/-0.87 (P=0.005), whereas two out of six (33.3%) scramble-injected BD mice improved and the severity score changed from 2.5+/-0.84 to 2.0+/-1.41 (P=0.203). Foxp3, ROR gamma t, IL-17A, IL-17F and tumor necrosis factor-alpha were also influenced in IL-6 siRNA-injected BD mice compared with scramble-injected BD mice. Adoptive transfer of CD4+CD25+ cells to BD mice affected the decrease of IL-6 serum levels and were dependent on CD4+CD25+ cell numbers. These results showed that downregulation of IL-6 improved the inflammatory symptoms in BD mice through upregulation of regulatory T cells and inhibition of Th17 cells.