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Objective: To investigate the relationship between genes and clinical characteristics in children and adolescents with metastatic differentiated thyroid cancer (caDTC). Methods: A cross sectional study. A total of 67 caDTC patients with lymph node metastasis or distant metastasis in Peking Union Medical College Hospital from December 2020 to December 2022 were included, according to the inclusion and exclusion criteria. Then the differences in clinicopathologic features and iodine intake were compared among different genomes, and the age subgroups divided by the age of 12 were further analyzed. Results: Among the 67 cases of caDTC, the diagnosed age [ M ( Q 1 , Q 3 )]was 13.2 (9.7, 16.9) years old, with 23 males and 44 females. There were 68.7% (46/67) of patients have distant metastasis (M1 stage). Pathogenic or potentially pathogenic gene variants were detected in 68.7% (46/67) of the patients, with RET or NTRK fusion (RET/NTRK) being the most common [43.3%(29/67)], BRAF V600E mutation followed [19.4%(13/67)].There was only 1 caDTC with NRAS Q61R mutation. The patients were divided into RET/NTRK fusion group ( n =29), BRAF mutation group ( n =12), other mutation group ( n =4), and non-mutation group ( n =21) (1 patient was not included in the gene mutation subgroup comparison due to the presence of NRAS Q61R mutation and BRAF V600E mutation). The comparison of gene feature groups showed that compared to the BRAF mutation group, caDTC with RET/NTRK fusion tended to have a lower age at diagnosis [12.6(9.3, 15.9) vs 17.2(15.5, 18.1) years old, P <0.001], the proportion of mutation load≥2 was higher (10.4% vs 8.3%, P =0.027), with statistically significant difference. Among 46 M1 stage patients, 71.7% (33/46) had initial iodine intake, and 30.4% (14/46) developed radioiodine-refractory (RAIR). In age group comparison, the<12 year old group had a higher proportion of male patients (51.9% vs 22.5%, P =0.013) and a lower incidence of BRAF V600E mutations (0 vs 32.5%, P <0.001) compared to the≥12 year old group, and the differences were statistically significant. Conclusions: The incidence of RET/NTRK fusion ranks first in metastatic caDTC, featured with younger age at diagnosis and higher rate of distant metastasis. Although most metastatic lesions initially consume iodine, they are prone to RAIR. Attention should be paid to the potential role of RET/NTRK fusion in the invasion and iodine resistance of young caDTC patients.

SUMMARYGroup A Streptococcus (GAS), also known as Streptococcus pyogenes , is a clinically well-adapted human pathogen that harbors rich virulence determinants contributing to a broad spectrum of diseases. GAS is capable of invading epithelial, endothelial, and professional phagocytic cells while evading host innate immune responses, including phagocytosis, selective autophagy, light chain 3-associated phagocytosis, and inflammation. However, without a more complete understanding of the different ways invasive GAS infections develop, it is difficult to appreciate how GAS survives and multiplies in host cells that have interactive immune networks. This review article attempts to provide an overview of the behaviors and mechanisms that allow pathogenic GAS to invade cells, along with the strategies that host cells practice to constrain GAS infection. We highlight the counteractions taken by GAS to apply virulence factors such as streptolysin O, nicotinamide-adenine dinucleotidase, and streptococcal pyrogenic exotoxin B as a hindrance to host innate immune responses., Competing Interests: The authors declare no conflict of interest.

The single-nucleotide polymorphism (SNP) rs2235371 ( IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequencing of an interval containing IRF6 in 159 Han Chinese with NSCL/P. This study revealed that the SNP rs12403599, within the IRF6 promoter, is associated with all phenotypes of NSCL/P, especially nonsyndromic cleft lip (NSCLO) and a subphenotype of it, microform cleft lip (MCL). This association was replicated in 2 additional much larger cohorts of cases and controls from the Han Chinese. Conditional logistic analysis indicated that association of rs2235371 with NSCL/P was lost if rs12403599 was excluded. rs12403599 contributes the most risk to MCL: its G allele is responsible for 38.47% of the genetic contribution to MCL, and the odds ratios of G/C and G/G genotypes were 2.91 and 6.58, respectively, for MCL. To test if rs12403599 is functional, we carried out reporter assays in a fetal oral epithelium cells (GMSM-K). Unexpectedly, the risk allele G yielded higher promoter activity in GMSM-K. Consistent with the reporter studies, expression of IRF6 in lip tissues from NSCLO and MCL patients with the G/G phenotype was higher than in those from patients with the C/C phenotype. These results indicate that rs12403599 is tagging the risk haplotype for NSCL/P better than rs2235371 in Han Chinese and supports investigation of the mechanisms by which the allele of rs12403599 affects IRF6 expression and tests of this association in different populations.

Various methods of evaluating a humectant's moisture retention have unique mechanisms. Hence, for designing advanced or efficient ingredients of cosmetic products, a clear understanding of differences among methods is required. The aim of this study was to analyze the moisture-retention capacity of glycerin, a common ingredient in cosmetic products. Specifically, this study applied gravimetric analysis, transepidermal water loss (TEWL) analysis, and differential scanning calorimetry (DSC) to examine the evaporation of glycerin solutions of different concentrations. The results revealed that the moisture-retention capacity of glycerin increased with the glycerin concentration from 0 to 60 wt%, and glycerin at concentration of 60-70 wt% did not exhibit weight change during the evaporation process. When the glycerin concentration exceeded 70 wt%, moisture sorption occurred in the glycerin solution. Furthermore, the results revealed a deviation between the evaporation rates measured using gravimetric analysis and those measured using TEWL analysis. However, normalizing the results of these analyses yielded the relative evaporation rates to water, which were consistent between these two analyses. DSC thermograms further confirmed the consistent results and identified two hydrated water microstructures (nonfreezable water and free water) in the glycerin solutions, which explained why the measured evaporation rate decreased with the glycerin concentration. These findings can be applied to prove the moisture-retention capacity of a humectant in cosmetic products by different measuring methods., (© 2022. The Author(s).)

Objectives: Tooth loss, which usually leads to malnutrition, is common in the elderly. However, limited information is available regarding its association with sarcopenia. This study aimed to investigate the relationship between loss of occlusal pairs of tooth and sarcopenia., Design: A cross-sectional retrospective study was performed., Setting: The elderly who participated in the National Basic Public Health Project in the Maigaoqiao Community Medical Center in Nanjing, Jiangsu Province, China., Participants: A total of 2850 individuals aged ≥60 years were enrolled., Measurements: Sarcopenia was defined according to the criteria proposed by the Asian Working Group for Sarcopenia. A trained dentist assessed oral health status and counted the number of present teeth. Logistic regression analyses were performed to evaluate the association between the loss of occlusal pairs and sarcopenia., Results: The prevalence of sarcopenia was 7.1% (201/2850). Univariate logistic regression analysis showed that loss of occlusal pairs was associated with sarcopenia [anterior occlusal pairs (AOPs): odd ratio (OR) = 1.292, 95% confidence interval (CI) = 1.158-1.442; posterior occlusal pairs (POPs): OR = 1.147, 95% CI = 1.018-1.221]. Multivariate logistic regression analysis indicated that loss of POPs was still an independent risk for sarcopenia (OR = 1.108, 95% CI = 1.007-1.220) after adjustment for traditional confounders. Subgroup analysis showed that loss of POPs was more significantly linked to sarcopenia in those with advanced age (≥80years) (OR = 1.307, 95% CI = 1.116-1.532) and in females (OR = 1.165, 95%CI = 1.038-1.308). Compared to individuals with ≥5 occluding pairs of POPs, those with <5 occluding pairs of POPs had a higher incidence of sarcopenia., Conclusions: Loss of POPs is associated with an increased risk of sarcopenia in the elderly in a Chinese population. Further research on the mechanism of the observed causal relationship is needed., Competing Interests: The authors declare no conflicts of interest.

Silver diamine fluoride (SDF) is used topically to prevent or arrest dental caries and has been tested clinically in toddlers to elderly adults. Following SDF application, small quantities of silver can be swallowed and absorbed. To monitor silver concentrations, pharmacokinetic studies can be performed. However, pharmacokinetic studies are time-consuming, resource intensive, and challenging to perform in young children. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict silver disposition in children. The PBPK model for silver was developed using Simcyp software (version 17.0) based on information obtained from literature sources. The predictive performance of the model was assessed by comparing the predicted PK profiles and parameters with the observed data from published rat and human data following intravenous or oral silver administration. The predicted silver concentrations were within 2-fold of observed blood and tissue silver concentrations in rats and within the 95% confidence interval of observed plasma silver concentrations in healthy human adults. The PBPK model was applied to the pediatric population by accounting for developmental physiological changes. For a given SDF dose, the simulated peak silver concentrations were 5.2-, 4.3-, 2.7-, and 1.3-fold higher in children aged 1 to 2, 2 to 4, 5 to 10, and 12 to 17 y, respectively, compared to adults. As silver is reportedly excreted in the bile, the half-life of silver was comparable in all ages and plasma and tissue silver concentrations were predicted to return to baseline levels within 2 wk after SDF application. The simulation in children suggests that conventional SDF application to teeth to prevent or arrest dental caries results in plasma and tissue silver concentrations lower than toxic concentrations. PBPK modeling offers a novel approach to studying dental exposures in younger children, where pharmacokinetic studies would be difficult to conduct.

Background: Clinical outcomes of patients undergoing a cardiac implantable electronic device (CIED) implantation following a recent non-device related infection are unknown., Aim: To evaluate the clinical outcomes of patients with recent infection before CIED implantation., Methods: Consecutive patients (N = 1237) were classified as patients with recent infection (N = 72) and without recent infection (N = 1165). A recent infection was established by reviewing medical records, including symptoms and clinical manifestations, diagnosis of systemic inflammatory response syndrome, and quick Sequential Organ Failure Assessment (qSOFA) score. Multiple stepwise logistic regression analysis was used to identify independent predictors of in-hospital all-cause mortality., Findings: During nearly three years of follow-up, 17 patients had CIED infection (1.4%), and the incidence of CIED infection did not significantly differ between patients with and without recent infection according to symptoms and clinical manifestations (2.8% vs 1.3%, respectively; not significant). However, patients with recent infection had a significantly higher in-hospital mortality rate compared to those without recent infection (22.2% vs 0.9%, respectively; P < 0.05). In multivariate analysis, predictors of in-hospital mortality were recent infection before CIED implantation (odds ratio: 20.3; 95% confidence interval: 8.4-49.3; P < 0.001) and end-stage renal disease (4.3; 1.4-12.8; P = 0.009)., Conclusion: A CIED implantation is feasible in patients with recent infection if the patient is afebrile and has received an adequate duration of antibiotic therapy. Participants in shared decision-making before implant should be advised that recent infection increases in-hospital mortality risk, especially in patients with a qSOFA score of ≥2., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Cardiac implantable electronic device (CIED) infection, a major complication of a CIED implant procedure, can prolong hospitalization and cause mortality., Aim: To evaluate the efficacy of a bundled skin antiseptic preparation for preventing infection after implantation of a complex CIED., Methods: This study analysed 1163 consecutive patients who had received a bundled skin antiseptic preparation before CIED implantation from July 2012 to December 2017. According to the complexity of the CIED implant procedure, the patients were divided into a complex CIED group (N = 370) and a non-complex CIED group (N = 793). A complex procedure was defined as a pacemaker replacement, implantation of implantable cardioverter defibrillator and cardiac resynchronization therapy, device upgrade, or lead revision., Findings: During a mean follow-up of 2.9 ± 1.7 years, CIED infection developed in 15 patients (1.3%), and the incidence of minor and major infection was 1.1% and 0.2%, respectively. The incidence of CIED infection did not significantly differ between the complex CIED group and the non-complex CIED group (1.1% vs 1.4%, respectively; non-significant). Multivariate analysis indicated that procedural complexity was not an independent predictor of CIED infection. After 2:1 propensity score matching, the matched non-complex CIED group and the matched complex CIED group still showed no significant difference in the incidence of CIED infection., Conclusion: Bundled skin antiseptic preparation is an effective and widely applicable strategy for decreasing infection risk after a complex CIED implantation., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We designed and fabricated a new type of superconducting quantum interference device (SQUID) susceptometers for magnetic imaging of quantum materials. The 2-junction SQUID sensors employ 3D Nb nano-bridges fabricated using electron-beam lithography. The two counter-wound balanced pickup loops of the SQUID enable gradiometric measurement and they are surrounded by a one-turn field coil for susceptibility measurements. The smallest pickup loop of the SQUIDs were 1 μm in diameter and the flux noise was around 1 μФ 0 /√Hz at 100 Hz. We demonstrate scanning magnetometry, susceptometry and current magnetometry on some test samples using these nano-SQUIDs.

Objective: To analyze the clinical characteristics and appropriate surgical procedures, and discuss the classification of congenital middle ear malformation. Methods: All cases were from the Center of Otorhinolaryngology, the Sixth Medical Center of Department of PLA General Hospital. All of these cases, including 26 male patients (ears) , 10 female patients (11 ears) , aged from 7 to 57 years old, had normal external auditory canal, tympanic membrane, conductive hearing loss, type A tympanogram and negative Gelle's test. Tympanoplasty was performed in all cases. The deformity was classified to three types,i.e., Type I (stapes foot plate mobility): Ⅰa, ossicular chain deformity with normal stapes suprastructure; Ⅰb, ossicular chain deformity with abnormal stapes suprastructure; Type Ⅱ (stapes foot plate fixation): Ⅱ a,normal ossicular chain, Ⅱ b, ossicular chain malformation; and Type Ⅲ: vestibular window osseous atresia or undeveloped, or with round window atresia. The malformation of type Ⅱ and Ⅲ may be accompanied with abnormal facial nerve. In addition, the papers on middle ear malformation published from 1982 to 2017 were analyzed retrospectively. The clinical data of 451 ears malformation were summarized. Results: According to the revisional classification criteria in 37 ear samples from our hospital, 20 ears were type I. 6 type Ⅰa cases were used PORP (partial ossicular replacement prosthesis) to reconstruct the ossicular chain; 14 type Ⅰb cases were used TORP (total ossicular replacement prosthesis) to reconstruct the ossicular chain. For the 5 ears of type Ⅱ, 2 of which were type Ⅱ a and 3 were type Ⅱ b. 4 ear samples of type Ⅱ were implanted with Piston ossicular prosthesis, 1 was implanted with TORP in which the ossificated foot plate was removed with periosteum preserved. 12 ear samples were type Ⅲ, with vestibular window osseous atresia, facial nerve malformation, and stapes suprastructure malformation. The pistons ossicular prosthesis were implanted in vestibular window in 3 ears with facial nerve covering vestibular window partially. The surgery had to be given up in 5 ears, and TORP was implanted in 4 ears at the opening with preserved periosteum at the beginning of the tympanic scala because of facial nerve covering vestibular window totally. 30 ears with complete follow-up data had no sensorineural hearing loss and the average air-bone conduction decreased 23.3±10.7 dB ( P <0.05).There were 234 ears of type Ⅰ in 451 ears of congenital middle ear malformation reported in the literature. 113 of which were type Ⅰa, the basic surgery was ossicular chain shaking and artificial or autogenous PORP implantation. Type Ⅰb was 121 ears, with autogenous or artificial TORP and PORP. Type Ⅱ was125 ears, including type Ⅱa 22 ears, Ⅱb 60 ears, and no subclassification for 43 ears. The surgery of type Ⅱ was the same as otosclerosis. The vestibular window atresia of type Ⅲ was 92 ears, the surgery of 17 ears had to be abandoned, the other ears underwent vestibular window, promontory or semicircular canal opening to reconstruct hearing with Piston, autogenous or artificial TORP. Conclusion: Referring to the classification of congenital middle ear malformation combining with appropriate surgical materials and methods, otologists can better understand and choose appropriate surgical method to the middle ear malformation.

Semiconducting 2D metal oxides have attracted great research interests for gas-sensing applications because of their considerable specific surface area and highly homogeneous surface. Developing a method for fabricating thin films of 2D metal oxides is crucial for minimizing the negative effects on sensing performance caused by slow diffusion. In this work, a simple, versatile, and highly reproducible self-assembly method is developed for fabricating monolayer film sensors made from metal oxide nanosheets with much superior sensing performance compared with their thick film counterparts. To prepare the monolayer film sensors, a monolayer film of metal oxide nanosheets, self-assembled at the air-water interface, is transferred onto a sensor substrate. The CuO monolayer sensors prepared with this self-assembly method show much improved gas sensitivity (sensor signal: 350% vs 100% at 5 ppm of H 2 S) and faster response and recovery rate (τ res : 20 s vs 110 s; τ rec : 120 s vs 320 s) than the thick film sensors prepared from the same sensing material. The enhanced sensing performance demonstrated by the monolayer film of CuO nanosheets is explained quantitively with a modified coupled reaction-diffusion model. Similar enhancement on gas-sensing performance is also observed for the ZnO-nanosheet-based monolayer sensors prepared by the same self-assembly method.

This paper reports synthesis of graphene oxide (GO) membranes with narrow interlayer free spacing on scalable polyester substrates using GO sheets prepared by Brodie's method. The GO membranes show interlayer free spacing of ∼3.2 Å with significantly improved hydrogen perm-selectivity than the GO membranes with the large inter-sheet spacing reported in literature.

Radioiodine-131((131)I) therapy as one of the post-surgical targeted therapies has been proven as an effective treatment modality in reducing the risk of recurrence and mortality in intermediate and high risk differentiated thyroid cancer (DTC). With increasing evidence over recent years, improvements in the management of DTC have been observed. In this review, several points and their influences on DTC decision making are discussed, including the purpose of (131)I therapy, evaluating system for risks and on-going response to therapy, as well as the significance of molecular features such as thyroglobulin, molecular pathology and nuclear medicine molecular imaging.

Background: Postherpetic neuralgia (PHN) is the most distressful complication of herpes zoster. PHN results in an impaired quality of life and higher healthcare utilization. Vitamin B12 has been proven to be effective in pain relief for various conditions., Objective: We conducted a systematic review and a meta-analysis to evaluate the efficacy of vitamin B12 supplementation in PHN patients., Methods: PubMed, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov registry were searched. Randomised control trials evaluating the efficacy and safety of vitamin B12 in PHN patients were selected. Eligible trials were abstracted and assessed for the risk of bias by two reviewers, and the results of pain indicators in the selected trials were analysed., Results: Four trials including 383 participants were published between 2013 and 2016. Compared with the placebo group, the Vitamin B12 group exhibited a significant decrease in the Numeric Rating Scale score, with a mean difference of -4.01 (95% confidence interval = -4.70 to -3.33). Vitamin B12 administration improved the quality of life of PHN patients with moderate quality evidence and significantly decreased the number of patients using analgesics., Conclusion: Vitamin B12 appears to be an attractive complementary therapy for PHN patients. Further investigation is needed before conclusive recommendations can be made., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The ventilatory efficiency represented cardiovascular, pulmonary, and musculoskeletal performance into an integrate index has been used as long-term and short-term prognostic variables in congestive heart failure. The heart failure patients post heart transplantation, whether the ventilatory efficiency was also normalized is still unknown., Methods: This was a cross-sectional study. We measured ventilation to carbon dioxide production slope and oxygen consumption in peak exercise (peak VO 2 ) by cardiopulmonary exercise test, which represented ventilatory efficiency and functional capacity respectively. Strength of hand grip, the 30-second chair stand test, and 6-minute walking test were also evaluated. Patients with ventilation to carbon dioxide production slope <30 were defined as the normal group; others were defined as the abnormal group. Independent t tests and paired t tests were used when appropriate. The level of statistical significance was set at .05., Results: There were 51 clinically stable post-heart transplantation patients (age 53 ± 12.4 years; 86.3% were male) at 65.14 ± 41.17 months after transplantation. The ventilation to carbon dioxide production slope was 29.2 ± 5.6, which significantly improved compared to that recorded 1 month after heart transplantation (32.6 ± 6.4). There were 20 patients in the abnormal group, characterized by lower 6-minute walking test distance (normal vs abnormal, 422.5 ± 97.8 vs 532.6 ± 87.6 m) and peak VO 2 (normal vs abnormal, 14.9 ± 5.3 vs 18.8 ± 5.1 mL/kg/min). The abnormal ventilation to carbon dioxide production slope was significantly correlated with 6-minute walking test distances in multivariate analyses., Conclusion: Our findings indicate that the ventilation to carbon dioxide production slope is partially abnormal among patients post-heart transplantation. A ventilation to carbon dioxide production slope above the normal range is characterized by a lower peak VO 2 during cardiopulmonary exercise test and lower 6-minute walking test distance. The ventilation to carbon dioxide production slope is also significantly negatively correlated with peak VO 2 , peak work rate, and 6-minute walking test distance. The prognostic utility of the ventilation to carbon dioxide production slope for patients post-heart transplantation requires further investigation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The ventilatory efficiency and functional capacity measured by the cardiopulmonary exercise test (CPET) have been used as important prognostic variables in congestive heart failure. This study sought to identify whether these predictors before heart transplantation (HTX) play a key role in predicting adverse events in patients with heart failure after HTX., Methods: This was a retrospective cohort study design. HTX recipients were included for analysis. Ventilation to carbon dioxide production slope (VE/VCO 2 slope) and oxygen consumption (VO 2 ) during exercise were collected by CPET, which represented ventilator efficiency and functional capacity respectively. Cardiac-related events 2 years after HTX were recorded by chart review. We divided patients into 2 groups based on VE/VCO 2 slope = 34, peak VO 2  = 14 mL/kg/min and VO 2 at aerobic threshold (AT) = 11 mL/kg/min. Kaplan-Meier survival curves was used to represent the events rate between groups and Log rank test was used to test significance., Results: A total of 87 patients after HTX were included. Mean (SD) age was 48 (11) years and 73 were male; 28 subjects suffered from events, and 76 cardiac events were recorded. The mean (SD) data of peak VO 2 , VO 2 at AT, and VE/VCO 2 slope analyzed from CPET were 17.8 (5.6) mL/kg/min, 15.4 (4.4) mL/kg/min, and 33.1 (8.2) mL/kg/min, respectively. Lower VO 2 at AT contributed to increase events rate (P < .05)., Conclusion: Aerobic capacity may better predict 2-year cardiac events in patients after HTX. Strategies to improve aerobic capacity should be focused on in the cohort., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Researchers have suggested that combining topical fluoride with an antiseptic to reduce cariogenic bacteria may be more effective than fluoride application alone in preventing dental caries. In previous studies, povidone iodine (PVP-I), a widely used bactericidal antiseptic, and sodium fluoride (NaF), used to foster remineralization of enamel, were applied sequentially topically and shown to be safe and effective. The study aim was to characterize the kinetics of iodine and fluoride following topical application of a single combination PVP-I and NaF anticaries varnish in healthy adults. Sixteen participants (aged 23 to 57 y) participated in a pharmacokinetics study following the application of 0.4 mL varnish containing 10% (w/v) PVP-I and 5% (w/v) NaF. Serum and urine samples were collected at various time points over 24 h following application of varnish. Iodine and fluoride concentrations were analyzed, and for each time point, baseline concentrations were subtracted from observed values. Following varnish application, 2 of 16 participants had nearly undetectable baseline-corrected iodine and fluoride levels, suggesting minimal absorption, lack of release of iodine and fluoride from the varnish, or inconsistent dosing. The average peak concentrations were 57 ± 33 ng/mL iodine and 60 ± 34 ng/mL (0.060 ± 0.034 ppm) fluoride and occurred within 3 h of application. The average elimination half-life was 5.5 ± 1.4 h and 3.1 ± 1.6 h for iodine and fluoride, respectively. Renal clearance of iodine and fluoride was similar to literature values. No adverse events related to the study varnish were observed by the investigative team or reported by the participants. In this study, serum fluoride and iodine transiently increased but were within normal range 24 h after application of the varnish. This study has shown that the combination of PVP-I and NaF in a proposed anticaries varnish was well tolerated. Knowledge Transfer Statement: This clinical study demonstrated that a dental varnish combining 10% (w/v) povidone iodine and 5% (w/v) sodium fluoride is well tolerated. Serum fluoride and iodine transiently increased but were within normal range after 24 h. Further studies should be conducted to assess the efficacy of a combination in preventing dental caries, especially in high-risk populations.

Background: As Mycobacterium tuberculosis is an aerobic microbe, hyperbaric oxygen therapy (HBOT) could trigger progression from latent tuberculous infection (LTBI) to active tuberculosis (TB) disease., Objective: To evaluate the effect of HBOT on TB reactivation., Design: Our study sample was from the National Health Insurance Research Database containing one million beneficiaries. We identified a group of patients who underwent HBOT, and matched this group with individuals without HBOT. We compared the incidence of activation of TB between these two groups., Results: A total of 2258 patients were identified, with each group comprising 1129 patients. One year after exposure to hyperbaric oxygen, the number of cases of active TB was significantly higher in the HBOT group than in the non-HBOT group (11 cases vs. 1 case, P = 0.006). Multiple regression analysis showed that HBOT was the only statistically significant contributor to TB activation., Conclusion: HBOT is likely to trigger the reactivation of TB. High-risk patients should undergo the tuberculin skin test or interferon-gamma release assays before HBOT to identify patients with LTBI.

Background: The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection., Methods: A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100β, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared., Results: Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg-1 h-1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min-1 m-2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P<0.05)., Conclusions: During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol., Clinical Trial Registration: NCT02113358., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.

Background and Purpose: Inflammation comprises important aspects of large-artery atherosclerosis (LAA) stroke pathophysiology. YKL-40 is a new and emerging biomarker that is associated with both acute and chronic inflammations. Elevated serum concentrations of YKL-40 have been reported in patients with atherosclerosis and other cardiovascular diseases. This study investigates whether serum YKL-40 concentrations on admission can predict 3-month clinical outcomes after LAA stroke., Methods: We recruited control patients (n=85) and those with LAA stroke (n=141) according to the TOAST classification system. The modified Rankin scale at 3 months after stroke was used to evaluate the prognosis. The prognostic accuracy was assessed by the receiver operating characteristic curve., Results: Serum YKL-40 level was significantly higher for LAA patients than for controls (P<.001). Patients with poor outcomes (n=36) had significantly increased serum YKL-40 concentrations on admission (P=.01). High YKL-40 levels predicted poor functional outcome (OR=6.47, P=.02). Moreover, the combination of YKL-40 level and the NIHSS score could improve the prognostic accuracy of the NIHSS in predicting functional outcome (combined areas under the curve, 0.87; 95% CI, 0.80-0.94; P<.001)., Conclusions: The level of serum YKL-40 is a significant and independent biomarker to predict the clinical outcome of LAA stroke., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The Ti/Zr-based metallic glasses (MGs) with various Cu contents are prepared, with nominal compositions of Ti 45 Zr 40 Si 15 (Cu-free), Ti 45 Zr 40 Si 10 Cu 5 (low-Cu), and Ti 45 Zr 20 Cu 35 (high-Cu). The mechanical properties, corrosion resistance, and in-vitro biocompatibility of these MGs are investigated by means of nano-indentation, electrochemical analyses, MTS assays and inductively coupled plasma mass spectrometry, as well as in-vivo biocompatibility in terms of scanning electron microscopy, micro-CT scans and histological observations. The results show that the electrochemical activity and biocompatibility of the MGs are sensitive to the Cu content. Following the electrocorrosion tests, an increase in ion concentration is observed in high-Cu MG. Eight independent in-vitro tests show that the higher ion concentration leads to a lower cell viability. The twelve-week in-vivo tests show that the Cu-free MGs can be a promising material for developing bio-implants. The high-Cu MG would release Ti and Zr ions with insignificant Cu ion following corrosion testing, enhancing an increased local osteoclast activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The prevalence of thyroid nodules, especially differentiated thyroid cancer, has increased during the past decades. With the consideration of increasing prevalence of the diseases, American Thyroid Association (ATA) updated the guidelines for adult patients with thyroid nodules and differentiated thyroid carcinoma (DTC) in 2015. The aim of the new guidelines was to minimize potential harm from overtreatment in majority of patients at low risk for diseasespecific mortality and morbidity while appropriately treat and monitor those patients at higher risk. The updates of contents in new ATA guidelines are interpreted in this article, including the contents about screening, diagnosis and treatment plan of nodules, initial surgical treatment of DTC, the evaluation and treatment of DTC after surgery, follow-up and diagnosis and treatment of recurrence, persistence, and distant metastasis of DTC.

Objectives: To assess the prognostic performance of a new N classification that incorporates the log odds of positive lymph nodes (LODDS) into the routinely used pathological N classification for oral squamous cell carcinoma (OSCC) patients., Design: Retrospective cohort study utilising LODDS into pN category was performed, and the AJCC TNM stage and T-New N-M stage were compared with respect to 5-year disease-specific survival (DSS) rates. The discriminability was evaluated from the linear trend chi-square test, Akaike information criterion (AIC) and Harrell's c-statistic., Setting: Medical centrer in Taiwan., Participants: A total of 463 patients received primary surgery and neck dissection between 2004 and 2013 for OSCC., Main Outcome Measures: The discriminability for 5-year DSS rates., Results: The median follow-up period was 54 months, the mean patient age was 54 ± 11 years and 428 patients (92.4%) were male. The patients with higher LODDS had worse 5-year DSS rates. Incorporation of LODDS into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for 5-year DSS with a lower AIC (1883 versus 1897), and higher prediction accuracy (Harrell's c-statistic: 0.768 versus 0.764)., Conclusions: By utilising a merger of the LODDS and pN classifications to create a new N classification has better discriminatory and predictive ability than pathological TNM staging and could help identify high-risk patients for intense adjuvant therapy., (© 2017 John Wiley & Sons Ltd.)

The effect of CYP2D6 genotype on the dose-exposure relationship for atomoxetine has not been well characterized in children. Children 6-17 years of age diagnosed with attention-deficit hyperactivity disorder (ADHD) were stratified by CYP2D6 genotype into groups with 0 (poor metabolizers [PMs], n = 4), 0.5 (intermediate metabolizers [IMs], n = 3), one (extensive metabolizer [EM]1, n = 8) or two (EM2, n = 8) functional alleles and administered a single 0.5 mg/kg oral dose of atomoxetine (ATX). Plasma and urine samples were collected for 24 (IM, EM1, and EM2) or 72 hours (PMs). Dose-corrected ATX systemic exposure (area under the curve [AUC]0-∞ ) varied 29.6-fold across the study cohort, ranging from 4.4 ± 2.7 μM*h in EM2s to 5.8 ± 1.7 μM*h, 16.3 ± 2.9 μM*h, and 50.2 ± 7.3 μM*h in EM1s, IMs, and PMs, respectively (P < 0.0001). Simulated steady state profiles at the maximum US Food and Drug Administration (FDA)-recommended dose suggest that most patients are unlikely to attain adequate ATX exposures. These data support the need for individualized dosing strategies for more effective use of the medication., (© 2015 American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Oxygen uptake efficiency slope (OUES) has been shown as a predictor of stable heart failure (HF) survival. However, there is a lack of evidence for end-stage HF., Objectives: We aimed to investigate the prognostic value of OUES in end-stage HF patients., Methods: The study design was a retrospective cohort. End-staged HF patients who had cardiopulmonary exercise testing (CPET) for evaluation between 2004 and 2009 were included. The primary outcomes were cardiac death and heart transplantation. The independent survival predictors were determined using Cox regression hazard model adjusted for demographics, New York Heart Association (NYHA) classification, medication, and left ventricular ejection fraction (LVEF). The Kaplan-Meier survival curves and log-rank test were used. Probability values less than .05 were considered significant., Results: Mean age of the 128 patients was 50 ± 12 years and 93 were male. Mean LVEF was 23% ± 9%. Forty-three subjects suffered cardiac events (5 cardiac deaths and 38 urgent heart transplantations) during the 2-year follow-up period. Cox regression indicated that OUES and diuretics were significant predictors of 2-year survival, although peak oxygen uptake and ventilatory equivalent of carbon dioxide were not. Patients with high OUES (≥1.6) had a higher survival rate (P < .001; odds ratio [OR], 13.10; 95% confidence interval [CI], 3.30-58.63). The Kaplan-Meier curves show survival was significantly higher in those with OUES ≥1.6., Conclusions: OUES might be an aid in prognosis of patients with end-stage HF and useful in the assessment of patients unable to perform maximal exercise testing., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Research has shown that Toll-like receptor 4 (TLR4) is important in immune responses to some helminth parasites. In sheep, variation in the PAMP region of TLR4 may result in structurally and thus functionally different TLR4 molecules, and this may consequently lead to variation in the TLR4 response to parasite infections. This study involved three separate, but related sheep breeds (Merino, Polwarth and Corriedale sheep) and a total of 885 lambs from five New Zealand farms that underwent a mixed field-challenge from gastro-intestinal parasites. Faecal samples were collected at approximately 4 and 9 months of age and faecal egg counts (FECs) for Nematodirus spp. and Strongyle species determined, along with the total number of eggs per gram (EPG). Analysis of the five farms collectively revealed an association (P=0.023) between the presence of TLR4 variant *02 (mean 24 EPG) and the absence of the variant (mean 32 EPG) at 9 months of age. Conversely the presence of *03 had a significantly (P=0.047) higher mean Nematodirus spp. FEC (mean 42 EPG) compared to the absence (mean 28 EPG) at 9 months of age. More associations were revealed when the data were split according to the dominant faecal parasite species. With a predominantly Trichostrongylus spp. FEC group of lambs at 9 months of age, the presence of TLR4 variant *02 was found to have significantly (P=0.003) lower Nematodirus spp. FEC (mean 4 EPG), and also significantly (P=0.033) lower total FEC (mean 312 EPG) when compared to sheep without the variant (mean 15 EPG and 449 EPG, respectively). The presence of TLR4 variant *03 and *04 were associated or tended to be associated (P=0.010 and P=0.088, respectively) with higher Nematodirus spp. FEC (mean 25 EPG and 22 EPG, respectively) when compared to lambs without the variant (mean 10 EPG and 11 EPG, respectively). These results suggest that TLR4 variation may be affecting the immune response to gastro-intestinal parasites in sheep, although principally to Nematodirus spp. infections and not Strongyle species infections., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the incidence rates and risk of sudden sensorineural hearing loss among patients with depressive disorders., Method: Data for 27 547 patients with newly diagnosed depressive disorders and 27 547 subjects without depressive disorders between 2001 and 2008 were yielded from the Taiwan National Health Insurance Research Database. Sudden sensorineural hearing loss incidence at the end of 2011 was determined. Cumulative incidence and adjusted hazard ratio were computed., Results: Sudden sensorineural hearing loss incidence was 1.45 times higher in the depressive disorders group compared to the non-depressive disorders group (p = 0.0041), with an adjusted hazard ratio of 1.460. A significant increased risk of developing sudden sensorineural hearing loss was noted in patients with diabetes mellitus, chronic kidney disease and hyperlipidaemia (p < 0.05)., Conclusion: The results suggest an increased risk of developing sudden sensorineural hearing loss in patients with depressive disorders. Co-morbidities such as diabetes mellitus, chronic kidney disease and hyperlipidaemia significantly aggravated the risk. Depressive disorders might be considered a risk factor for sudden sensorineural hearing loss. It remains to be seen whether control of depressive disorders can decrease the incidence of sudden sensorineural hearing loss in patients with depressive disorders.

The genetic relationships among 27 pineapple [Ananas comosus (L.) Merr.] cultivars and lines were examined using 16 simple sequence repeat (SSR) markers. The number of alleles per locus of the SSR markers ranged from 2 to 6 (average 3.19), for a total of 51 alleles. Similarity coefficients were calculated on the basis of 51 amplified bands. A dendrogram was created according to the 16 SSR markers by the unweighted pair-group method. The banding patterns obtained from the SSR primers allowed most of the cultivars and lines to be distinguished, with the exception of vegetative clones. According to the dendrogram, the 27 pineapple cultivars and lines were clustered into three main clusters and four individual clusters. As expected, the dendrogram showed that derived cultivars and lines are closely related to their parental cultivars; the genetic relationships between pineapple cultivars agree with the genealogy of their breeding history. In addition, the analysis showed that there is no obvious correlation between SSR markers and morphological characters. In conclusion, SSR analysis is an efficient method for pineapple cultivar identification and can offer valuable informative characters to identify pineapple cultivars in Taiwan.

Syzygium samarangense (Blume) Merr. & Perry (wax apple) is an important commercial fruit tree in Southeast Asia. Here, microsatellite markers were developed to evaluate genetic diversity and distinguish cultivars in this species. In total, 161 microsatellite loci with sufficient flanking sequences to design primer sets were isolated from wax apple using a magnetic bead-enrichment method. Fifty-eight primer sets were designed based on the flanking sequences of each single sequence repeat (SSR) locus and were tested using 14 wax apple cultivars/lines. Twenty SSR loci were found to be polymorphic and transferable across the 14 wax apple cultivars/lines. The number of alleles and effective number of alleles detected per locus ranged from 4 to 12 and from 1.697 to 9.800, respectively. The expected heterozygosity ranged from 0.150 to 0.595 (mean = 0.414). Polymorphism information content values ranged from 0.502 to 0.866 (mean = 0.763). These new microsatellite loci will be of value for characterization of genetic diversity in wax apples and for the identification of cultivars.

Obesity is the major risk factor for early puberty, but emerging evidence indicates other factors including psychosocial stress. One key brain region notable for its role in controlling calorie intake, stress, and behavior is the amygdala. Early studies involving amygdala lesions that included the medial nucleus advanced puberty in rats. More recently it was shown that a critical site for lesion-induced hyperphagia and obesity is the posterodorsal subnucleus of the medial amygdala (MePD), which may explain the advancement of puberty. Glutamatergic activity also increases in the MePD during puberty without a corresponding γ-aminobutyric acid (GABA)ergic change, suggesting an overall activation of this brain region. In the present study, we report that neurotoxic lesioning of the MePD advances puberty and increases weight gain in female rats fed a normal diet. However, MePD lesioned rats fed a 25% nonnutritive bulk diet also showed the dramatic advancement of puberty but without the increase in body weight. In both dietary groups, MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior. Chronic GABAA receptor antagonism in the MePD from postnatal day 21 for 14 days also advanced puberty, increased socialization, and decreased play fighting without altering body weight, whereas glutamate receptor antagonism delayed puberty and decreased socialization without affecting play fighting. In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake. MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.

Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.

Microbial life inhabits deeply buried marine sediments, but the extent of this vast ecosystem remains poorly constrained. Here we provide evidence for the existence of microbial communities in ~40° to 60°C sediment associated with lignite coal beds at ~1.5 to 2.5 km below the seafloor in the Pacific Ocean off Japan. Microbial methanogenesis was indicated by the isotopic compositions of methane and carbon dioxide, biomarkers, cultivation data, and gas compositions. Concentrations of indigenous microbial cells below 1.5 km ranged from <10 to ~10(4) cells cm(-3). Peak concentrations occurred in lignite layers, where communities differed markedly from shallower subseafloor communities and instead resembled organotrophic communities in forest soils. This suggests that terrigenous sediments retain indigenous community members tens of millions of years after burial in the seabed., (Copyright © 2015, American Association for the Advancement of Science.)

The effect of grain boundaries (GBs), in particular twin boundaries (TBs), on CdTe polycrystalline thin films is studied by conductive atomic force microscopy (C-AFM), electron-beam-induced current (EBIC), scanning Kelvin probe microscopy (SKPM), electron backscatter diffraction (EBSD), and scanning transmission electron microscopy (STEM). Four types of CdTe grains with various densities of {111} Σ3 twin boundaries (TBs) are found in Cl-treated CdTe polycrystalline thin films: (1) grains having multiple {111} Σ3 TBs with a low angle to the film surface; (2) grains having multiple {111} Σ3 TBs parallel to the film surfaces; (3) small grains on a scale of not more than 500 nm, composed of Cd, Cl, Te, and O; and (4) CdTe grains with not more than two {111} Σ3 TBs. Grain boundaries (including TBs) exhibit enhanced current transport phenomena. However, the {111} Σ3 TB is much more beneficial to micro-current transport. The enhanced current transport can be explained by the lower electron potential at GBs (including TBs) than the grain interiors (GIs). Our results open new opportunities for enhancing solar cell performances by controlling the grain boundaries, and in particular TBs.

Competition between humans and livestock for cereal and legume grains makes it challenging to provide economical feeds to livestock animals. Recent increases in corn and soybean prices have had a significant impact on the cost of feed for pig producers. The utilization of byproducts and alternative ingredients in pig diets has the potential to reduce feed costs. Moreover, unlike ruminants, pigs have limited ability to utilize diets with high fiber content because they lack endogenous enzymes capable of breaking down nonstarch polysaccharides into simple sugars. Here, we investigated the feasibility of a transgenic strategy in which expression of the fungal cellulase transgene was driven by the porcine pancreatic amylase promoter in pigs. A 2,488 bp 5'-flanking region of the porcine pancreatic amylase gene was cloned by the genomic walking technique, and its structural features were characterized. Using GFP as a reporter, we found that this region contained promoter activity and had the potential to control heterologous gene expression. Transgenic pigs were generated by pronuclear microinjection. Founders and offspring were identified by PCR and Southern blot analyses. Cellulase mRNA and protein showed tissue-specific expression in the pancreas of F1 generation pigs. Cellulolytic enzyme activity was also identified in the pancreas of transgenic pigs. These results demonstrated the establishment of a tissue-specific promoter of the porcine pancreatic amylase gene. Transgenic pigs expressing exogenous cellulase may represent a way to increase the intake of low-cost, fiber-rich feeds.

This paper presents systematical investigations, including electrochemical activity, MTT cell assay and in vivo test, on the biocompatibility of three metallic glasses. The electrochemical behaviors and the cell toxicity of two newly developed TiZr-based metallic glasses (MGs), Ti42Zr40Si15Ta3 and Ti40Zr40Si15Cu5, with lower or without unfavorable elements are systematically investigated. Results show that the MGs with low Cu content exhibit a low electrochemical response. Cytotoxicity tests for the MGs and the mediums after the potential state test are evaluated with in vitro MTT assays. The solid specimens and the mediums after the potential state test for the pure Ti, Ti42Zr40Si15Ta3 and Ti40Zr40Si15Cu5 exhibit no significant cytotoxicity in the MTT test, while the tested medium for Ti45Cu35Zr20 MG shows lower cell viability. The inductively coupled plasma-mass spectrometry (ICP-MS) results also indicate that the Cu-rich sample released a significant amount of ions which may be the major factor causing the low viability in the MTT test. The good healing condition and the low C-reactive protein (CRP) index for the implanted New Zealand rabbits in a one-month in vivo test also show the satisfactory short-term biocompatibility of the TiZr-based MGs. The electrochemical measurements, in vitro, and in vivo experiments confirm that the developed TiZr-based MGs with lower Cu content (≦5%) are promising for biomedical purposes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: Non-invasive prenatal testing for fetal trisomy 21 (T21) by massively parallel shotgun sequencing (MPSS) is available for clinical use but its efficacy is limited by several factors, e.g. the proportion of cell-free fetal DNA in maternal plasma and sequencing depth. Existing algorithms discard DNA reads from the chromosomes for which testing is not being performed (i.e. those other than chromosome 21) and are thus more susceptible to diluted fetal DNA and limited sequencing depth. We aimed to describe and evaluate a novel algorithm for aneuploidy detection (genome-wide normalized score (GWNS)), which normalizes read counts by the proportions of DNA fragments from chromosome 21 in normal controls., Methods: We assessed the GWNS approach by comparison with two existing algorithms, i.e. Z-score and normalized chromosome value (NCV), using theoretical approximations and computer simulations in a set of 86 cases (64 euploid and 22 T21 cases). We then validated GWNS by studying an expanded set of clinical samples (n = 208). Finally, dilution experiments were undertaken to compare performance of the three algorithms (Z-score, NCV, GWNS) when fetal DNA concentration was low., Results: At fixed levels of significance and power, GWNS required a smaller fetal DNA proportion and fewer total MPSS reads compared to Z-score or NCV. In dilution experiments, GWNS also outperformed the other two methods by reaching the correct diagnosis with the lowest range of fetal DNA concentrations (GWNS, 3.83-4.75%; Z-score, 4.75-5.22%; NCV, 6.47-8.58%)., Conclusion: Our results demonstrate that GWNS is comparable to Z-score and NCV methods regarding the performance of detecting fetal T21. Dilution experiments suggest that GWNS may perform better than the other methods when fetal fraction is low., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Clustered regularly interspaced short palindromic repeats (CRISPR) are composed of numerous repeat-spacer units and are considered a prokaryotic defence system against foreign nucleic acids. Since antibiotic-resistant genes are frequently encoded in foreign nucleic acids, the aim of this study was to test whether erythromycin susceptibility in group A streptococcus (Streptococcus pyogenes) is associated with characteristics of CRISPR elements. Erythromycin susceptibility of 330 isolates collected between 1997 and 2003 was analysed. Among 29 emm types, emm12, emm75 and emm92 showed significant changes in erythromycin-resistance rates. By sequencing the spacers from two CRISPR loci, spacer contents in emm12, emm75 and emm92 strains were associated with erythromycin susceptibility. Strains with fewer spacers were more resistant to erythromycin. Moreover, in emm4 strains, which showed no significant change in their annual erythromycin-resistance rate, CRISPR type and number of spacers were not correlated with erythromycin susceptibility. These results highlight a novel association between CRISPR spacer content and erythromycin susceptibility in group A streptococcus., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Objective: To investigate whether tobacco smoking increases the risk of tuberculosis (TB) recurrence and identify factors associated with TB recurrence among adults who had successfully completed anti-tuberculosis treatment in Taipei, Taiwan., Methods: Recurrence was defined as a new clinical or microbiological diagnosis of TB requiring the start of a new course of treatment in a patient who had satisfactorily completed treatment for a previous TB episode. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) for recurrence., Results: We followed 5567 adults for recurrence after successful anti-tuberculosis treatment. The mean age was 58.5 years; 62.9% were male. Overall, 84 (1.5%) had a recurrence of TB during follow-up. The incidence of TB recurrence was 4.9 episodes/1000 person-years of follow-up. Cox proportional hazards regression showed that after controlling for other variables, the risk of TB recurrence among subjects who smoked >10 cigarettes a day was double that of never/former smokers. Other independent risk factors significantly associated with TB recurrence were homelessness (aHR 3.75, 95%CI 1.17-12.07), presence of comorbidities (aHR 2.66, 95%CI 1.22-5.79) and a positive acid-fast bacilli smear (aHR 2.27, 95%CI 1.47-3.49)., Conclusion: Smoking >10 cigarettes a day was significantly associated with TB recurrence. To reduce the risk of recurrence, we recommend including effective measures of smoking cessation in TB control programmes, as recommended by the World Health Organization Stop TB Strategy.

Background: Ventilatory equivalent (ventilation/CO2 production, VE/VCO2) slope has been suggested to be a much more accurate predicator than peak oxygen consumption (VO2) during exercise for prognosis in patients with heart failure. However, patients tested were predominately male., Methods: To investigate whether peak VO2 and VE/VCO2 slope predict the prognosis of female patients with heart failure, we retrospectively collected data of 39 female candidates referred for heart transplantation (HTx) from 2004 to 2011. Both peak VO2 and VE/VCO2 slope were obtained from the results of an exercise pulmonary function test. The outcome was death or mechanical devices implantation or HTx. Logistic regression was used for data analysis., Results: Mean age and heart failure survival score were 55.8 ± 13.7 years and 7.3 ± 0.7, respectively. Each increment of VE/VCO2 slope decreased 2-year event-free rate (odds ratio [OR] = 0.88, 95% confidence interval [CI] = 0.79 to 0.98) in the female group. The predictions of VE/VCO2 slope for 1-year event-free survival did not reach statistical significance (OR = 0.92, 95% CI = 0.84 to 1.00). On the other hand, peak VO2 was not a strong predictor for 1- and 2-year event-free survival (OR = 1.22 and 1.16, 95% CI = 0.96 to 1.55 and 0.94 to 1.44, respectively)., Conclusions: Impairment in exercise ventilation holds a clinical and long-term prognostic impact in female patients with heart failure. The role of peak VO2 during exercise in prognostic prediction among the cohort should be further investigated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases., Methods: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1., Results: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies., Conclusion: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Thin film metallic glasses (TFMGs) are demonstrated to exhibit excellent surface flatness, high corrosion resistance and satisfactory hydrophobic properties. Moreover, the antimicrobial and biocompatibility abilities of TFMGs are examined and the results are compared with the behavior of pure Ag and 316L stainless steel. Three TFMGs, Al48Ag37Ti15, Zr54Ti35Si11, and Zr59Ti22Ag19, are prepared by sputtering to assess the antimicrobial performance against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, which are the most common nosocomial infection pathogens. Experimental results show that the antimicrobial effect of the Al- or Ag-containing AlAgTi and ZrTiAg TFMGs is similar to that of the pure Ag coating. The ZrTiSi TFMG with no Ag or Al shows poor antimicrobial capability. The physical properties of highly smooth surface and hydrophobic nature alone are not sufficient to result in promising antimicrobial ability. The chemical metal ion release still plays a major role, which should be born in mind in designing biomedical devices., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real-time indicator of active kidney damage, including acute kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail., Hypothesis/objectives: The goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease., Animals: Client-owned dogs with renal disease (57) and control dogs without any disease (12) were examined., Methods: Serum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively., Results: Serum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver-operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time., Conclusion: sNGAL is a useful prognostic marker when evaluating dogs with CKD., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

For the first time, a tubular asymmetric ceramic-carbonate dual phase membrane was prepared by a centrifugal casting technique and used for high temperature CO2 separation. This membrane shows high CO2 permeation flux and permeance.