Urethral diverticulum in pregnancy

AbstractUrethral diverticulum is rare in pregnancy. There is no clear guideline on the management of urethral diverticulum in pregnancy, but most cases were managed conservatively. We report a case of urethral diverticulum in a primigravida woman, who presented with anterior vaginal swelling at 14 weeks of gestation. She was managed conservatively and the cyst (approximately 8 cm × 13 cm) was aspirated during the early stage of labor. However her labor did not progress during the second stage, which resulted in an emergency cesarean section. She underwent diverticulectomy at 1 month postpartum because of the recurrence of the swelling and persistent discomfort. We believe that her dystocia may have been caused by factors other than the diverticulum. As previously described in literature, we concluded that, even in pregnant women with a large urethral diverticulum, vaginal delivery can still be considered with prior aspiration during the early stage of labor

An Exploratory Study of Response Shift in Health-Related Quality of Life and Utility Assessment Among Patients with Osteoarthritis Undergoing Total Knee Replacement Surgery in a Tertiary Hospital in Singapore

AbstractObjectiveTo investigate the influence of response shift (RS) on health-related quality of life (HRQOL) and utility assessment among patients undergoing total knee replacement.MethodsConsenting patients undergoing total knee replacement were interviewed to determine their HRQOL by using the six-dimensional health state short form, derived from SF-36, and the EuroQol five-dimensional questionnaire at baseline (pretest 1) and the six-dimensional health state short form, derived from SF-36, at 6 (pretest 2) and 18 months after surgery (post-test). RS was studied by using a “then-test” approach by contacting participants 18 months after surgery and asking them to evaluate their HRQOL at baseline (then-test 1) and at 6 (then-test 2) and 18 months after surgery. RS was calculated as the score difference between pretest and then-test scores for a given time point. Relationships between RS and external variables were explored by using univariate and multiple liner regression analyses.ResultsIn 74 subjects (63% response rate, median age 68 years), median (interquantile range) six-dimensional health state short form, derived from SF-36, scores for then-tests at baseline (0.48 [0.42–0.49]) and at 6 months (0.72 [0.66–0.79]) after surgery were significantly different from respective pretest scores (0.61 [0.58–0.68] at baseline, P = 0.000; 0.69 [0.63–0.72] at 6 months, P = 0.000), showing RS at both time points. RS at baseline (0.14 [0.08–0.20]) was significantly larger than that at 6 months (−0.05 [0.14 to 0.00], P = 0.000). EuroQol five-dimensional questionnaire pretest and then-test scores at baseline also differed significantly (0.69 [0.17–0.73] vs. −0.18 [−0.23 to 0.00], P = 0.000). RS at baseline was not affected by assessed demographic or medical variables. RS at 6 months was greater in subjects with more years of education (16% of variance in multiple liner regression, P < 0.01).ConclusionRS was present and impacted HRQOL and utility assessment among patients undergoing total knee replacement before and 6 months after surgery

A novel procedure for precise quantification of Schistosoma japonicum eggs in bovine feces

Schistosomiasis japonica is a zoonosis with a number of mammalian species acting as reservoir hosts, including water buffaloes which can contribute up to 75% to human transmission in the People's Republic of China. Determining prevalence and intensity of Schistosoma japonicum in mammalian hosts is important for calculating transmission rates and determining environmental contamination. A new procedure, the formalin-ethyl acetate sedimentation-digestion (FEA-SD) technique, for increased visualization of S. japonicum eggs in bovine feces, is described that is an effective technique for identifying and quantifying S. japonicum eggs in fecal samples from naturally infected Chinese water buffaloes and from carabao (water buffalo) in the Philippines. The procedure involves filtration, sedimentation, potassium hydroxide digestion and centrifugation steps prior to microscopy. Bulk debris, including the dense cellulosic material present in bovine feces, often obscures schistosome eggs with the result that prevalence and infection intensity based on direct visualization cannot be made accurately. This technique removes nearly 70% of debris from the fecal samples and renders the remaining debris translucent. It allows improved microscopic visualization of S. japonicum eggs and provides an accurate quantitative method for the estimation of infection in bovines and other ruminant reservoir hosts. We show that the FEA-SD technique could be of considerable value if applied as a surveillance tool for animal reservoirs of S. japonicum, particularly in areas with low to high infection intensity, or where, following control efforts, there is suspected elimination of schistosomiasis japonica.This work was partially supported by the following grants: The National High Technology Research and Development Program of China (grant No. 2007AA02Z153), and National Science and Technology Major Program (grant Nos. 2009ZX10004-302, 2008ZX10004-011)

FY2014 Annual Report

Abstract Background This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20–39 years old. Methods All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity. Results Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as < 231 ng/dL). Multivariate logistic regression revealed the odds of low testosterone was significantly greater with increasing SSB consumption (Q4 [≥442 kcal/day] vs. Q1 [≤137 kcal/day]), adjusted odds ratio [aOR] = 2.29, p = 0.041]. After adjusting for possible confounding variables, BMI was an independent risk factor for low testosterone level; subjects with BMI ≥ 25 kg/m2 had a higher risk of having a low testosterone level than those with BMI < 25 kg/m2 (aOR = 3.68, p = 0.044). Conclusion SSB consumption is significantly associated with low serum testosterone in men 20–39 years old in the United States

CD133-Positive Cells Might Be Responsible for Efficient Proliferation of Human Meningioma Cells

Owing to lack of appropriate model systems, investigations of meningioma biology have come to a stop. In this study, we developed a comprehensive digestion method and defined a culture system. Using this method and system, primary meningioma cells in conditioned suspension medium and a hypoxic environment could be amplified in spheres and were passaged for more than ten generations. Meningioma sphere cells were positive for meningioma cell markers and negative for markers of neural cell types. Importantly, we found the cells expressed the stem cell marker, CD133, but not nestin. All of the tumor sphere cell populations showed a slower degree of cell proliferation than that of human glioma cells and fetal neural stem cells (NSCs). Further studies showed that the proliferative rate was positively correlated with CD133 expression. The higher the CD133 expression, the faster the cell proliferation. With the increase in cell generations, the cell proliferation rate gradually slowed down, and CD133 expression also decreased. Single CD133+ cells rather than CD133− cells could form spheres. Thus, the results above indicated that those cells expressing CD133 in spheres might be stem-like cells, which may be responsible for efficient amplification of human meningioma cells. Decreased expression of CD133 may lead to the failure of long-term passaging

Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK

Fructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose. The decrease of calcium at contact sites between ER and lysosome renders the inhibited TRPV accessible to bind the lysosomal v-ATPase that then recruits AXIN:LKB1 to activate AMPK independently of AMP. Genetic depletion of TRPVs blocks glucose starvation-induced AMPK activation in cells and liver of mice, and in nematodes, indicative of physical requirement of TRPVs. Pharmacological inhibition of TRPVs activates AMPK and elevates NAD(+) levels in aged muscles, rejuvenating the animals' running capacity. Our study elucidates that TRPVs relay the FBP-free status of aldolase to the reconfiguration of v-ATPase, leading to AMPK activation in low glucose

Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate

人类遗传学家James V. Neel在1962年首次提出了“节俭基因”这一概念，认为现今人类导致包括肥胖症、糖尿病和高血压等代谢障碍的基因是因为生理系统为了适应远古环境食物富足和食物缺乏的周期性改变而筛选出的，可以让远古人类在食物富足的短暂时期中快速增肥，以应对随时将到来的食物缺乏时期。这类基因在当时环境下有很大的优越性，但对于当今食物富足的社会则截然相反。这篇论文中林圣彩教授团队揭示了乙酰转移酶TIP60通过乙酰化脂肪合成途径的代谢酶lipin 1并促进其向内质网转运，从而提高脂肪合成速率，揭示了TIP60作为一个“节俭基因”的功能和作用机制。该研究阐明了脂肪合成途径中首个受蛋白质乙酰化修饰调控的途径，揭示了TIP60作为经典转录调控因子之外的又一重要生物学功能，为开发防治肥胖症及其相关代谢紊乱疾病提供了新的药物作用靶点。博士后李阳、博士生宋林涛和硕士生孙玉是该论文的共同第一作者。【Abstract】Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense fatty acids and connect to the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at the Ser86 phosphorylation site of acetyltransferase Tip60 (Tip60SA/SA) display remarkably reduced body fat mass, and Tip60SA/SA females fail to nurture pups to adulthood due to severely reduced milk TAGs. Mechanistically, fatty acids stimulate Tip60-dependent acetylation and endoplasmic reticulum translocation of phosphatidic acid phosphatase lipin 1 to generate diacylglycerol for TAG synthesis, which is repressed by deacetylase Sirt1. Inhibition of Tip60 activity strongly blocks fatty acid-induced TAG synthesis while Sirt1 suppression leads to increased adiposity. Genetic analysis of loss-of-function mutants in Saccharomyces cerevisiae reveals a requirement of ESA1, yeast ortholog of Tip60, in TAG accumulation. These findings uncover a conserved mechanism linking fatty acid sensing to fat synthesis.This work was supported by grants from the National Natural Science Foundation of China (#31690101, #31430094, #31600961 and #31571214) and National Key Research and Development Project of China (2016YFA0502001). 该研究受到了国家自然科学基金和中国国家重点研发计划项目的资助

ULK1/2所构成的信号节点除控制细胞自噬外还控制葡萄糖代谢通路

文章简介在细胞感受到环境中营养物质和生长因子的提供量发生改变后,代谢通路的重编程对于维持此时胞内的稳态是非常重要的过程。ULK1和ULK2是传递外界应激信号至自噬发生的重要整合因子。本项研究发现,在缺少氨基酸和生长因子时,ULK1/2能直接磷酸化多个糖酵解相关的酶,包括己糖激酶(HK)、国家自然科学基金重点项目；国家科技部(973课题)；国家基础科学人才培养基金等的经费支持

Antifungal susceptibility profiles and drug resistance mechanisms of clinical Candida duobushaemulonii isolates from China

Candida duobushaemulonii, type II Candida haemulonii complex, is closely related to Candida auris and capable of causing invasive and non-invasive infections in humans. Eleven strains of C. duobushaemulonii were collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of C. duobushaemulonii was done to determine their genotypes. Furthermore, C. duobushaemulonii strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three C. duobushaemulonii could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 μg/ml. One isolate showed a high MIC value of ≥64 μg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins. FUR1 variation may result in C. duobushaemulonii with high MIC to 5-flucytosine. Candida duobushaemulonii mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment