Identification and characterization of dysregulated P-element induced wimpy testis-interacting RNAs in head and neck squamous cell carcinoma.

It is clear that alcohol consumption is a major risk factor in the pathogenesis of head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanism underlying the pathogenesis of alcohol-associated HNSCC remains poorly understood. The aim of the present study was to identify and characterize P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) and PIWI proteins dysregulated in alcohol-associated HNSCC to elucidate their function in the development of this cancer. Using next generation RNA-sequencing (RNA-seq) data obtained from 40 HNSCC patients, the piRNA and PIWI protein expression of HNSCC samples was compared between alcohol drinkers and non-drinkers. A separate piRNA expression RNA-seq analysis of 18 non-smoker HNSCC patients was also conducted. To verify piRNA expression, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed on the most differentially expressed alcohol-associated piRNAs in ethanol and acetaldehyde-treated normal oral keratinocytes. The correlation between piRNA expression and patient survival was analyzed using Kaplan-Meier estimators and multivariate Cox proportional hazard models. A comparison between alcohol drinking and non-drinking HNSCC patients demonstrated that a panel of 3,223 piRNA transcripts were consistently detected and differentially expressed. RNA-seq analysis and in vitro RT-qPCR verification revealed that 4 of these piRNAs, piR-35373, piR-266308, piR-58510 and piR-38034, were significantly dysregulated between drinking and non-drinking cohorts. Of these four piRNAs, low expression of piR-58510 and piR-35373 significantly correlated with improved patient survival. Furthermore, human PIWI-like protein 4 was consistently upregulated in ethanol and acetaldehyde-treated normal oral keratinocytes. These results demonstrate that alcohol consumption may cause dysregulation of piRNA expression in HNSCC and in vitro verifications identified 4 piRNAs that may be involved in the pathogenesis of alcohol-associated HNSCC

Efecto del tamaño de pólipo y de los exudados de corales sobre la dinámica de picoeucariotas en un ambiente controlado

We examined the ability of scleractinian corals with different polyp sizes to remove picoeukaryotes by predation and the effect of coral exudates on picoeukaryote growth. Experiments were conducted by adding picoeukaryotes to Stylophora pistillata (SP) and Montipora stellata (MS). Within six hours the picoeukaryote concentration in the SP and MS tanks was significantly lower than the control without corals. SP showed higher overall activity than MS, and the particle removal activity of MS decreased in light conditions. Picoeukaryotes exposed to SP exudates grew significantly denser than those exposed to MS exudates or those in water without coral exudates. Dissolved organic carbon concentrations in the SP tanks were also significantly higher. We concluded that the picoeukaryote removal rates were higher in S. pistillata than in M. stellata, and coral exudates can reciprocally enhance picoeukaryote growth.Hemos estudiado la capacidad de corales escleractinios con diferentes tamaños de pólipo de depredar picoplancton eucariótico, y también el efecto de los exudados de los corales sobre el crecimiento de picoplancton eucariótico. Los experimentos se realizaron añadiendo picoplancton eucariótico a Stylophora pistillata (SP) y Montipora stellata (MS). Después de 6 horas, las concentraciones de picoplancton eucariótico en los tanques de SP y MS fueron significativamente reducidas, en comparación con las del tanque control sin coral. SP mostró en general una actividad depredadora algo más grande que MS, y éste redujo su actividad en condiciones de luz. Los picoeucariotas expuestos a exudados de SP llegaron a concentraciones más altas que cuando fueron expuestos a exudados de MS o a agua sin corales. La concentración de carbono orgánico disuelto en los tanques de SP también fué significativamente más alta. Se concluye que las tasas de depredación sobre los picoeukaryotes fueron más altas con S. pistillata que con M. stellata, y que los exudados del coral pueden recíprocamente mejorar el crecimiento de picoplancton eucariótico

Significant association of hematinic deficiencies and high blood homocysteine levels with burning mouth syndrome

Background/PurposeBurning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa in the absence of clinically apparent mucosal alterations. In this study, we evaluated whether there was an intimate association of the deficiency of hemoglobin (Hb), iron, vitamin B12, or folic acid; high blood homocysteine level; and serum gastric parietal cell antibody (GPCA) positivity with BMS.MethodsBlood Hb, iron, vitamin B12, folic acid, and homocysteine concentrations and the serum GPCA level were measured in 399 BMS patients and compared with the corresponding levels in 399 age- and sex-matched healthy control individuals.ResultsWe found that 89 (22.3%), 81 (20.3%), 10 (2.5%), and six (1.5%) BMS patients had deficiencies of Hb (men: <13 g/dL, women: <12 g/dL), iron (<60 μg/dL), vitamin B12 (<200 pg/mL), and folic acid (<4 ng/mL), respectively. Moreover, 89 (22.3%) BMS patients had abnormally high blood homocysteine level and 53 (13.3%) had serum GPCA positivity. BMS patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency; of abnormally elevated blood homocysteine level; or of serum GPCA positivity than the healthy control group (all p < 0.001 except for vitamin B12 deficiency, for which p = 0.004). However, no significant difference in frequency of folic acid deficiency (p = 0.129) was found between BMS patients and healthy control individuals.ConclusionWe conclude that there is a significant association of deficiency of Hb, iron, and vitamin B12; abnormally high blood homocysteine level; and serum GPCA positivity with BMS

Comparison of the Offspring Sex Ratio Between Cleavage Stage Embryo Transfer and Blastocyst Transfer

SummaryObjectiveTo compare the sex ratio of offspring born after cleavage stage embryo transfer and blastocyst transfer.Materials and MethodsIn this retrospective study of embryo transfer (ET), we included 473 offspring from 446 deliveries during the period January 2002 to December 2007. Statistical analysis was performed on the sex ratio of offspring resulting from day 3 cleavage stage embryo transfer and from sequential blastocyst culture transfer.ResultsIn total, 446 patient deliveries were included in this analysis. There were 251 singleton pregnancies, 109 twin pregnancies, and four triplet pregnancies. The total number of offspring was 473, of which 118 resulted from day 3 ETs, and 355 resulted from blastocyst ETs. At our center, the influence on the sex ratio of cleavage stage ET and blastocyst-stage ET showed a bias towards males in both cases. The overall female to male ratio for offspring resulting from day 3 ETs was not significantly higher than the same ratio for offspring resulting from blastocyst ETs (p = 0.24; odds ratio, 0.762). The female to male ratio for either singleton births or multiple deliveries was also not significantly different between day 3 ETs and blastocyst ETs.ConclusionThe sex ratio was influenced by cleavage stage ET and blastocyst-stage ET. In both cases, there was a bias towards males. In addition, when blastocyst ET was compared with day 3 ET, there was no further increase in the percentage of male offspring

DC-SIGN (CD209) Promoter −336 A/G (rs4804803) Polymorphism Associated with Susceptibility of Kawasaki Disease

Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is the most effective therapy for KD to reduce the prevalence of coronary artery lesion (CAL) formation. Recently, the α2, 6 sialylated IgG was reported to interact with a lectin receptor, specific intracellular adhesion molecule-3 grabbing nonintegrin homolog-related 1 (SIGN-R1) in mice and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) in human, and to trigger an anti-inflammatory cascade. This study was conducted to investigate whether the polymorphism of DC-SIGN (CD209) promoter −336 A/G (rs4804803) is responsible for susceptibility and CAL formation in KD patients using Custom TaqMan SNP Genotyping Assays. A total of 521 subjects (278 KD patients and 243 controls) were investigated to identify an SNP of rs4804803, and they were studied and showed a significant association between the genotypes and allele frequency of rs4804803 in control subjects and KD patients (P = 0.004 under the dominant model). However, the promoter variant of DC-SIGN gene was not associated with the occurrence of IVIG resistance, CAL formation in KD. The G allele of DC-SIGN promoter −336 (rs4804803) is a risk allele in the development of KD

Exercise training with negative pressure ventilation improves exercise capacity in patients with severe restrictive lung disease: a prospective controlled study

BACKGROUND: Exercise training is of benefit for patients with restrictive lung disease. However, it tends to be intolerable for those with severe disease. We examined whether providing ventilatory assistance by using negative pressure ventilators (NPV) during exercise training is feasible for such patients and the effects of training. METHODS: 36 patients with restrictive lung disease were prospectively enrolled for a 12-week multidisciplinary rehabilitation program. During this program, half of them (n:18; 60.3 ± 11.6 years; 6 men; FVC: 32.5 ± 11.7% predicted ) received regular sessions of exercise training under NPV, whilst the 18 others (59.6 ± 12.3 years; 8 men; FVC: 37.7 ± 10.2% predicted) did not. Exercise capacity, pulmonary function, dyspnea and quality of life were measured. The primary endpoint was the between-group difference in change of 6 minute-walk distance (6MWD) after 12 weeks of rehabilitation. RESULTS: All patients in the NPV-exercise group were able to tolerate and completed the program. The between-group differences were significantly better in the NPV-exercise group in changes of 6MWD (34.1 ± 12.7 m vs. -32.5 ± 17.5 m; P = 0.011) and St George Score (−14.5 ± 3.6 vs. 11.8 ± 6.0; P < 0.01). There was an improvement in dyspnea sensation (Borg’s scale, from 1.4 ± 1.5 point to 0.8 ± 1.3 point, P = 0.049) and a small increase in FVC (from 0.85 ± 0.09 L to 0.91 ± 0.08 L, P = 0.029) in the NPV-exercise group compared to the control group. CONCLUSION: Exercise training with NPV support is feasible for patients with severe restrictive lung diseases, and improves exercise capacity and health-related quality of life

Nocturnal CPAP improves walking capacity in COPD patients with obstructive sleep apnoea

BACKGROUND: Exercise limitation is an important issue in patients with chronic obstructive pulmonary disease (COPD), and it often co-exists with obstructive sleep apnoea (overlap syndrome). This study examined the effects of nocturnal continuous positive airway pressure (CPAP) treatment on walking capacity in COPD patients with or without obstructive sleep apnoea. METHODS: Forty-four stable moderate-to-severe COPD patients were recruited and completed this study. They all underwent polysomnography, CPAP titration, accommodation, and treatment with adequate pressure. The incremental shuttle walking test was used to measure walking capacity at baseline and after two nights of CPAP treatment. Urinary catecholamine and heart rate variability were measured before and after CPAP treatment. RESULTS: After two nights of CPAP treatment, the apnoea-hypopnoea index and oxygen desaturation index significantly improved in both overlap syndrome and COPD patients, however these changes were significantly greater in the overlap syndrome than in the COPD group. Sleep architecture and autonomic dysfunction significantly improved in the overlap syndrome group but not in the COPD group. CPAP treatment was associated with an increased walking capacity from baseline from 226.4 ± 95.3 m to 288.6 ± 94.6 m (P < 0.05), and decreased urinary catecholamine levels, pre-exercise heart rate, oxygenation, and Borg scale in the overlap syndrome group. An improvement in the apnoea-hypopnoea index was an independent factor associated with the increase in walking distance (r = 0.564). CONCLUSION: Nocturnal CPAP may improve walking capacity in COPD patients with overlap syndrome. TRIAL REGISTRATION: NCT0091426

Feasibility of Bispectral Index-Guided Propofol Infusion for Flexible Bronchoscopy Sedation: A Randomized Controlled Trial

There are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists.After administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation.The proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group.BIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference.ClinicalTrials. gov NCT00789815

Introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3D polymerase

AbstractIn 1998, an enterovirus 71 (EV71) epidemic in Taiwan resulted in 78 deaths; however, the molecular basis of EV71 pathogenicity remains poorly understood. Comparison of the deduced amino acid sequences in 3D polymerases of EV71clinical isolates showed the T251V or T251I substitution from 1986 and 1998 outbreaks. An EV71 replicon system showed that introducing an I251T mutation did not affect luciferase activities at 35 °C when compared with wild type; however, lower luciferase activities were observed when they were incubated at 39.5 °C. In addition, the I251T mutation in the EV71 infectious clone not only reduced viral replication at 39.5 °C in vitro but also decreased the virulence of the mouse adaptive strain MP4 in neonatal mice in an i.p. infection model. Therefore, these results suggested that the threonine at position 251 results in a temperature sensitivity phenotype of EV71 which may contribute to the attenuation of circulating strains