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To perform a mental health evaluation and an early psychological intervention for healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) epidemic, an online survey was conducted among 3055 HCWs in the paediatric intensive care units (PICUs) of 62 hospitals in China on March 26, 2020, by the Neurology and Sedation Professional Group, Emergency Department, Paediatrics Branch, Chinese Medical Association. The questionnaire was divided into three parts, including general information, the Impact of Event Scale-Revised (IES-R), and the Depression Anxiety Stress Scale-21 (DASS-21). The results show that a total of 970 HCWs (45.99%) were considered to meet the clinical cut-off scores for posttraumatic stress (PTS), and the proportions of participants with mild to extremely severe symptoms of depression, anxiety and stress were 39.69%, 36.46% and 17.12%, respectively. There was no significant difference in the psychological impact among HCWs of different genders. Married HCWs were 1.48 times more likely to have PTS than unmarried HCWs (95% Cl: 1.20–1.82, p <0.001). Compared with junior professional title participants, the PTS-positive rate of HCWs with intermediate professional titles was 1.91 times higher (90% Cl: 1.35–2.70, p<0.01). Those who had been in contact with confirmed COVID-19 cases were 1.40 times (95% Cl: 1.02–1.92, p <0.05) more likely to have PTS than those who did not have contact with COVID-19 cases or did not know the relevant conditions. For depression, the proportion of HCWs with intermediate professional titles was significantly higher, at 1.65 times (90% Cl: 1.17–2.33, p <0.01) that of those with junior professional titles. The depression of HCWs at work during the epidemic was 1.56 times that of HCWs on vacation (95% Cl: 1.03–2.37, p <0.05), and their anxiety was 1.70 times greater (95% Cl: 1.10–2.63, p <0.05). Participants who had been in contact with confirmed COVID-19 cases had more pronounced anxiety, 1.40 times that of those who did not have contact with COVID-19 cases or did not know the relevant conditions (95% Cl: 1.02–1.92, p <0.05). There was no significant correlation between the variables and the positive results of stress symptoms. In total, 45.99%, 39.69%, 36.46% and 17.12% of PICU HCWs were affected by PTS, depression, anxiety and stress, respectively, to varying degree. Married status, intermediate professional titles and exposure history were independent risk factors for PTS. Intermediate professional titles and going to work during the epidemic were independent risk factors for depression, and going to work and exposure history during the epidemic were independent risk factors for anxiety. In the face of public health emergencies, HCWs not only specialize in paediatric intensive care but also, as a high-risk group, must actively take preventive measures and use mitigation strategies. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the factors of rapid attenuation of graft endothelium in the early stage after penetrating keratoplasty (PKP), with a view to guiding patients with PKP to better long-term outcomes. This study included 226 patients who underwent PKP with follow-up time >1 year at the Qingdao Eye Hospital of Shandong First Medical University from January 2018 to June 2020. Medical records were retrospectively studied, and donor factors, patient factors, and surgical factors were comparatively analyzed to clarify those affecting the rapid decay of graft endothelium after PKP. The median time between excision and death >60 min and patient age >60 years were risk factors for endothelial cell loss (ECL) rate >30% at 1 month postoperatively. However, a higher percentage of patients with donor age ≤60 years and Optisol preservation solution had endothelial cell density (ECD) >2000 cells/mm2 in the graft at postoperative 1 year. A year after the surgery, patients with corneal endothelial decompensation and immune rejection were at risk for ECD < 1000 cells/mm2. The combined operations had a significant effect on the ECL in the early postoperative period. Patients who underwent combined extracapsular cataract extraction or intraocular lens implantation had a significantly higher rate of ECL at postoperative 1 month than other patients, and no significant effect at postoperative 1 year. However, patients without combined operations have a higher probability of maintaining a high level of graft ECD. The graft diameter also affected postoperative ECL. In patients with a larger graft diameter, attenuation of ECD was slower. The ultimate goal of PKP is to maintain graft transparency for extended periods. The use of younger donors, minimizing unnecessary operation in the anterior chamber, and minimizing immune rejection may maintain a greater donor corneal endothelium in the long term. [ABSTRACT FROM AUTHOR]

Dietary fat is discussed to be critical in the development of non-alcoholic fatty liver disease. Here, we assess the effect of exchanging dietary fat source from butterfat to extra virgin olive oil on the progression of an already existing diet-induced non-alcoholic fatty liver disease in mice. Female C57BL/6J mice were fed a liquid butterfat-, fructose- and cholesterol-rich diet (BFC, 25E% from butterfat) or control diet (C, 12%E from soybean oil) for 13 weeks. In week 9, fat sources of some BFC- and C-fed mice were switched either to 25E% or 12E% olive oil (OFC and CO). Glucose and insulin tolerance tests were performed, and markers of liver damage and glucose metabolism were assessed. After 6 weeks of feeding, BFC-fed mice had developed marked signs of insulin resistance, which progressed to week 12 being not affected by the exchange of fat sources. Liver damage was similar between BFC- and OFC-fed mice. Markers of lipid metabolism and lipid peroxidation in liver and of insulin signaling in liver and muscle were also similarly altered in BFC- and OFC-fed mice. Taken together, our data suggest that exchanging butterfat with extra virgin olive oil has no effect on the progression of non-alcoholic fatty liver disease and glucose tolerance in mice. [ABSTRACT FROM AUTHOR]

Our analysis of thousands of movies and books reveals how these cultural products weave stereotypical gender roles into morality tales and perpetuate gender inequality through storytelling. Using the word embedding techniques, we reveal the constructed emotional dependency of female characters on male characters in stories. We call this narrative structure "Cinderella complex", which assumes that women depend on men in the pursuit of a happy, fulfilling life. Our analysis covers a substantial portion of narratives that shape the modern collective memory, including 7,226 books, 6,087 movie synopses, and 1,109 movie scripts. The "Cinderella complex" is observed to exist widely across periods and contexts, reminding how gender stereotypes are deeply rooted in our society. Our analysis of the words surrounding female and male characters shows that the lives of males are adventure-oriented, whereas the lives of females are romantic-relationship oriented. Finally, we demonstrate the social endorsement of gender stereotypes by showing that gender-stereotypical movies are voted more frequently and rated higher. [ABSTRACT FROM AUTHOR]

There is growing awareness within the scientific community of the strong connection between the inflammation in the intestine and the pathogenesis of Parkinson's disease (PD). In previous studies we developed a PD animal model exposing pup rats to permethrin (PERM) pesticide. Here, we intended to explore whether in our animal model there were changes in gut permeability, fecal microbiota and hepatic injury. Moreover, we tested if the co-treatment with an electrolyzed reduced (ERW) was effective to protect against alterations induced by PERM. Rats (from postnatal day 6 to 21) were gavaged daily with PERM, PERM+ERW or vehicle and gut, liver and feces were analyzed in 2-months-old rats. Increased gut permeability, measured by FITC-dextran assay, was detected in PERM group compared to control and PERM+ERW groups. In duodenum and ileum, concentration of occludin was higher in control group than those measured in PERM group, whereas only in duodenum ZO-1 was higher in control than those measured in PERM and PERM+ERW groups. Number of inflammatory focis and neutrophils as well as iNOS protein levels were higher in livers of PERM-treated rats than in those of PERM+ERW and control rats. Fecal microbiota analysis revealed that Lachnospira was less abundant and Defluviitaleaceae more abundant in the PERM group, whereas the co-treatment with ERW was protective against PERM treatment since the abundances in Lachnospira and Defluviitaleaceae were similar to those in the control group. Higher abundances of butyrate- producing bacteria such as Blautia, U.m. of Lachnospiraceae family, U.m. of Ruminococcaceae family, Papillibacter, Roseburia, Intestinimonas, Shuttleworthia together with higher butyric acid levels were detected in PERM+ERW group compared to the other groups. In conclusion, the PD animal model showed increased intestinal permeability together with hepatic inflammation correlated with altered gut microbiota. The positive effects of ERW co-treatment observed in gut, liver and brain of rats were linked to changes on gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Lactate is used to evaluate the prognosis of adult patients with trauma. However, the prognostic significance of admission serum lactate in the setting of pediatric traumatic brain injury (TBI) is still unclear. We aim to investigate the impact of admission lactate on the outcome in children with moderate to severe TBI. Methods: This retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale (GCS) of ≤13. Two hundred and thirteen patients were included in the analysis and 45 patients died in hospital. Results: Admission lactate and glucose were significantly higher in non-survivors than those in survivors (P < 0.05). Admission lactate was positively correlated with admission glucose and negatively correlated with GCS in all patients (n = 213), subgroup of isolated TBI (n = 112) and subgroup of GCS ≤ 8 (n = 133), respectively. AUCs of lactate could significantly predict the mortality and were higher than those of glucose in all patients, subgroup of isolated TBI and subgroup of GCS ≤ 8, respectively. Multivariate logistic regression showed that admission lactate (Adjusted OR = 1.189; 95% CI: 1.002–1.410; P = 0.047) was independently associated with mortality, while admission glucose (Adjusted OR = 1.077; 95% CI: 0.978–1.186; P = 0.133) wasn’t an independent risk factor of death. Elevated admission lactate (> 2 mmol/L) was associated with death, reduced 14-day ventilation-free days, 14-day ICU-free days and 28-day hospital-free days. Conclusions: Admission serum lactate can effectively predict the mortality of children with moderate to severe TBI. Elevated admission lactate is associated with death, reduced ventilator-free, ICU-free, and hospital-free days. Admission serum lactate could be used as a prognostic biomarker of mortality in children with moderate to severe TBI. [ABSTRACT FROM AUTHOR]

Background: China has a substantial tuberculosis (TB) disease burden and an aging population. Seniors have a higher risk of developing TB disease compared to younger age groups. Active case finding (ACF) could help identify seniors with TB disease. Methods: From March to June 2017, we included ACF during annual physical check-ups for persons aged ≥ 65 years in Bayi, Sichuan Province. Seniors with clinical TB symptoms (i.e., cough lasting ≥ 2 weeks and/or hemoptysis) or one or more risk factors (e.g., previous TB disease, diabetes, and heavy alcohol consumption) were offered chest x-rays. We used acid-Fast Bacilli smear and solid culture laboratory testing for TB confirmation. We calculated the yield (i.e., cases identified among seniors screened) and cost per new each TB case detected. Focus group-interviews were conducted with health care workers and seniors to evaluate project acceptability. Participation rates and acceptability were used to assess feasibility. Results: Of the 2,393 seniors residing in Bayi, 2,049 (85.6%) were enrolled in the pilot project. Of these seniors, 794 (38.7%) presented with at least one TB risk factor and 74 (3.6%) had symptoms consistent with active TB disease. Three seniors (0.2%)–each presenting with at least one risk factor—were diagnosed with active TB. The project yielded 146 TB cases per 100,000 seniors screened; the cost per case detected was $4,897. Most workers supported ACF if additional resources and staff could be provided. Seniors appreciated the convenience of this integrated health service approach. Conclusions: Although the yield was lower than expected, ACF appeared feasible in Bayi. Targeting seniors with at least one known TB risk factor could help detect previously unidentified TB cases. However, similar projects in communities with a higher TB prevalence are needed to further evaluate the yield and required resources prior to implementation on a larger scale. Findings from our pilot project should be combined with data from these future ACF projects to improve TB screening criteria. [ABSTRACT FROM AUTHOR]

To investigate the clinical characteristics, treatment, risk factors of occurrence and graft transparency of corneal epithelial defects after penetrating keratoplasty in patients with infectious keratitis. 594 patients (594 eyes) with infectious keratitis treated by penetrating keratoplasty at Shandong Eye Institute were reviewed retrospectively between January 2008 and January 2018. We investigated the demographic data, diameter and sources of graft, onset time, location, scope, time of healing and treatment of epithelial defects, as well as other postoperative complications and graft clarity. 114 of the 594 grafts (19.2%) that developed epithelial defects were included in the epithelial defects group, while the other 480 patients were classified in the non-defect group. The mean age of patients with epithelial defects was statistically greater than that of patients without epithelial defects (P = 0.006). The epithelial defects group accounted for a larger proportion of male patients (P<0.001). The proportion of patients with a graft diameter >9mm in the epithelial defect group (29.8%) was more than that in the non-defects group (16.3%) (P = 0.001). The incidence of epithelial defects significantly differed among the pathogenic causes of infectious keratitis (P = 0.002). The incidence of graft infection (21.1%, 9.2%, respectively, P<0.001) and graft dysfunction (7.9%, 2.5%, respectively, P = 0.012) in the epithelial defect group was higher than in the non-defects group. Multivariate logistic regression revealed that male sex (P = 0.001), age ≥ 60 years (P = 0.024), graft diameter >9mm (P = 0.001), bacterial (P = 0.039) and herpes simplex keratitis (P = 0.008), rheumatism (P = 0.031) and cancer treated with chemo- or radiotherapy (P = 0.032) were independent risk factors for epithelial defects. Graft clarity after epithelial defects were significantly differed between fungal and viral infections (P<0.001). We found that being an elderly male patient, a graft diameter >9 mm, bacterial and viral keratitis and systemic diseases (including rheumatism and cancer treated with chemo- or radiotherapy) were independent risk factors for postoperative epithelial defects. [ABSTRACT FROM AUTHOR]

We compared the clinical characteristics, treatments, and prognoses of fungal keratitis in patients with and without diabetes. Patients diagnosed with fungal keratitis at Shandong Eye Institute between January 2010 and December 2016 were retrospectively reviewed and classified as diabetic and nondiabetic groups. One-hundred-and-eleven patients (111 eyes) with diabetes and 740 patients (740 eyes) without diabetes were included. The diabetic patients showed significantly older (p< 0.05) and lower male:female ratio (p<0.05). Plants trauma was the primary risk factor in both groups, and there was no significant difference of pathogen type (the most common was Fusarium genus, followed by Alternaria and Aspergillus genera). Multivariate logistic regression analyses revealed that diabetes and topical glucocorticoid use were the independent risk factors for the severity of fungal keratitis. The recurrent infection rate between the diabetic and nondiabetic patients during the follow-up (6 to 24 months) after penetrating keratoplasty (PKP) was not significantly different. Although the recurrent epithelial defect, rejection, and best-corrected visual acuity were similar between the patients with matched bed/graft size (7.75/8.0 mm) in the two groups 1 year after PKP, the incidence of delayed re-epithelialization (>7 days) was significantly higher in diabetic patients (3/10 versus 2/43 in nondiabetic patients, p<0.05). More specially, the diabetic patients with the duration ≥10 years showed more significantly delayed re-epithelialization than those with the diabetic duration less than 10 years (3/5 versus 1/26, p<0.05). In conclusion, the diabetes mellitus is an independent risk factor that affect the severity of fungal keratitis. Corneal re-epithelialization was significantly delayed after PKP in the diabetic patients, especially with the duration ≥10 years. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is associated with altered maternal and placental vascular reactivity. Kv7 channels (encoded by KCNQ 1–5 genes) are a potential contributor to the regulation of vascular tone in CPAs (chorionic plate arteries) during normal pregnancy. The aim of this study is to establish the expression profile of KCNQ subunits in CPAs taken from women with preeclampsia or normotensive women and to examine the functional relevance of the Kv7 channels on an altered expression profile of KCNQ subunits. The effects of Kv7 channel modulators on CPAs were investigated by tension measurement. Quantitative PCR experiments were used to analyze the expression of KCNQ genes. Western blotting and immunofluorescence were both used to analyze the protein expression of Kv7 channels. Finally, in CPAs from normotensive women, the Kv7 channel blocker XE991 increased arterial basal tone and U46619-induced contraction, and pre-contracted CPAs (10−7 M U46619) exhibited significant relaxation following treatment with Retigabine(Kv7.2–7.5 activator) and BMS-204352(Kv7.2–7.5 activator). However, ICA-27243(selective KCNQ2 and KCNQ3 activator) and ML277(selective KV7.1 activator) had no significant effect on tension in the pre-contracted CPAs. Conversely, compared with CPAs from normotensive women, the effects of XE991 on basal tone and agonist (U46619)-induced contractions in CPAs from women with preeclampsia were markedly attenuated. Moreover, the relaxation effects of Retigabine and BMS-204352 on pre-contracted CPA vessels from women with pre-eclampsia were also markedly down-regulated. Interestingly, the relaxation ability of ICA-27243 in pre-contracted CPA vessels in women with pre-eclampsia was enhanced. The mRNA of KCNQ3 was specifically up-regulated, whereas those for KCNQ4 and KCNQ5 were down-regulated in CPAs from women with pre-eclampsia compared with those in normotensive women. Similar observations were found in a subsequent analysis of protein expression of KCNQ genes 3–5. Thus, down-regulated Kv7 channel function in tension regulation of CPAs in women with pre-eclampsia could be associated with considerably altered expression profiles of Kv7 subunits. [ABSTRACT FROM AUTHOR]

Environmental stress, such as oxygen deprivation, affects various cellular activities and developmental processes. In this study, we directly investigated Drosophila embryo development in vivo while cultured on a microfluidic device, which imposed an oxygen gradient on the developing embryos. The designed microfluidic device enabled both temporal and spatial control of the local oxygen gradient applied to the live embryos. Time-lapse live cell imaging was used to monitor the morphology and cellular migration patterns as embryos were placed in various geometries relative to the oxygen gradient. Results show that pole cell movement and tail retraction during Drosophila embryogenesis are highly sensitive to oxygen concentrations. Through modeling, we also estimated the oxygen permeability across the Drosophila embryonic layers for the first time using parameters measured on our oxygen control device. [ABSTRACT FROM AUTHOR]

Transformation is the main platform for genetic improvement and gene function studies in plants. However, the established somatic embryo transformation system for grapevines is time-consuming and has low efficiency, which limits its utilization in functional genomics research. Vitis amurensis is a wild Vitis species with remarkable cold tolerance. The lack of an efficient genetic transformation system for it has significantly hindered the functional identification of cold stress related genes in the species. Herein, an efficient method was established to produce transformed calli of V. amurensis. Segments of petioles from micropropagated plantlets of V. amurensis exhibited better capacity to differentiate calli than leaf-discs and stem segments, and thus was chosen as target tissue for Agrobacterium-mediated transformation. Both neomycin phosphotransferase II (NPTII) and enhanced green fluorescent protein (eGFP) genes were used for simultaneous selection of transgenic calli based on kanamycin resistance and eGFP fluorescence. Several parameters affecting the transformation efficiency were optimized including the concentration of kanamycin, Agrobacterium stains, bacterial densities, infection treatments and co-cultivation time. The transgenic callus lines were verified by checking the integration of NPTII gene into calli genomes, the expression of eGFP gene and the fluorescence of eGFP. Up to 20% of the petiole segments produced transformed calli after 2 months of cultivation. This efficient transformation system will facilitate the functional analysis of agronomic characteristics and related genes not only in V. amurensis but also in other grapevine species. [ABSTRACT FROM AUTHOR]

Objective: To calculate the yield and cost per diagnosed tuberculosis (TB) case for three World Health Organization screening algorithms and one using the Chinese National TB program (NTP) TB suspect definitions, using data from a TB prevalence survey of people aged 65 years and over in China, 2013. Methods: This was an analytic study using data from the above survey. Risk groups were defined and the prevalence of new TB cases in each group calculated. Costs of each screening component were used to give indicative costs per case detected. Yield, number needed to screen (NNS) and cost per case were used to assess the algorithms. Findings: The prevalence survey identified 172 new TB cases in 34,250 participants. Prevalence varied greatly in different groups, from 131/100,000 to 4651/ 100,000. Two groups were chosen to compare the algorithms. The medium-risk group (living in a rural area: men, or previous TB case, or close contact or a BMI <18.5, or tobacco user) had appreciably higher cost per case (USD 221, 298 and 963) in the three algorithms than the high-risk group (all previous TB cases, all close contacts). (USD 72, 108 and 309) but detected two to four times more TB cases in the population. Using a Chest x-ray as the initial screening tool in the medium risk group cost the most (USD 963), and detected 67% of all the new cases. Using the NTP definition of TB suspects made little difference. Conclusions: To “End TB”, many more TB cases have to be identified. Screening only the highest risk groups identified under 14% of the undetected cases,. To “End TB”, medium risk groups will need to be screened. Using a CXR for initial screening results in a much higher yield, at what should be an acceptable cost. [ABSTRACT FROM AUTHOR]

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis. [ABSTRACT FROM AUTHOR]

Content-based image retrieval (CBIR) techniques have currently gained increasing popularity in the medical field because they can use numerous and valuable archived images to support clinical decisions. In this paper, we concentrate on developing a CBIR system for retrieving brain tumors in T1-weighted contrast-enhanced MRI images. Specifically, when the user roughly outlines the tumor region of a query image, brain tumor images in the database of the same pathological type are expected to be returned. We propose a novel feature extraction framework to improve the retrieval performance. The proposed framework consists of three steps. First, we augment the tumor region and use the augmented tumor region as the region of interest to incorporate informative contextual information. Second, the augmented tumor region is split into subregions by an adaptive spatial division method based on intensity orders; within each subregion, we extract raw image patches as local features. Third, we apply the Fisher kernel framework to aggregate the local features of each subregion into a respective single vector representation and concatenate these per-subregion vector representations to obtain an image-level signature. After feature extraction, a closed-form metric learning algorithm is applied to measure the similarity between the query image and database images. Extensive experiments are conducted on a large dataset of 3604 images with three types of brain tumors, namely, meningiomas, gliomas, and pituitary tumors. The mean average precision can reach 94.68%. Experimental results demonstrate the power of the proposed algorithm against some related state-of-the-art methods on the same dataset. [ABSTRACT FROM AUTHOR]

Background: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. Methods: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. Results: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. Conclusion: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility. [ABSTRACT FROM AUTHOR]

Despite the burgeoning research on social entrepreneurship (SE), SE strategies remain poorly understood. Drawing on extant research on the social activism and social change, empowerment and SE models, we explore, classify and validate the strategies used by 2,334 social entrepreneurs affiliated with the world’s largest SE support organization, Ashoka. The results of the topic modeling of the social entrepreneurs’ strategy profiles reveal that they employed a total of 39 change-making strategies that vary across resources (material versus symbolic strategies), specificity (general versus specific strategies), and mode of participation (mass versus elite participation strategies); they also vary across fields of practice and time. Finally, we identify six meta-SE strategies―a reduction from the 39 strategies―and identify four new meta-SE strategies (i.e., system reform, physical capital development, evidence-based practices, and prototyping) that have been overlooked in prior SE research. Our findings extend and deepen the research into SE strategies and offer a comprehensive model of SE strategies that advances theory, practice and policy making. [ABSTRACT FROM AUTHOR]

Background: Massive infection caused by oomycete fungus Saprolegnia parasitica is detrimental to freshwater fish. Recently, we showed that copper sulfate demonstrated good efficacy for controlling S. parasitica infection in grass carp. In this study, we investigated the mechanism of inhibition of S. parasitica growth by copper sulfate by analyzing the transcriptome of copper sulfate—treated S. parasitica. To examine the mechanism of copper sulfate inhibiting S. parasitica, we utilized RNA-seq technology to compare differential gene expression in S. parasitica treated with or without copper sulfate. Results: The total mapped rates of the reads with the reference genome were 90.50% in the control group and 73.50% in the experimental group. In the control group, annotated splice junctions, partial novel splice junctions and complete novel splice junctions were about 83%, 3% and 14%, respectively. In the treatment group, the corresponding values were about 75%, 6% and 19%. Following copper sulfate treatment, a total 310 genes were markedly upregulated and 556 genes were markedly downregulated in S. parasitica. Material metabolism related GO terms including cofactor binding (33 genes), 1,3-beta-D-glucan synthase complex (4 genes), carboxylic acid metabolic process (40 genes) were the most significantly enriched. KEGG pathway analysis also determined that the metabolism-related biological pathways were significantly enriched, including the metabolic pathways (98 genes), biosynthesis of secondary metabolites pathways (42 genes), fatty acid metabolism (13 genes), phenylalanine metabolism (7 genes), starch and sucrose metabolism pathway (12 genes). The qRT-PCR results were largely consistent with the RNA-Seq results. Conclusion: Our results indicate that copper sulfate inhibits S. parasitica growth by affecting multiple biological functions, including protein synthesis, energy biogenesis, and metabolism. [ABSTRACT FROM AUTHOR]

Background: Needle core biopsy (NCB) is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate. Objective: To identify the influence of number of biopsies on NCB diagnostic accuracy. Methods: 153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis. Results: Using a 3-tier grading scheme (well, moderate and poor), the accuracy of NCB has no significant differences among different number of passes in HCC ≤5cm. For HCC >5≤8cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively). While in HCC>8cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively. Conclusions: The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5cm. [ABSTRACT FROM AUTHOR]

Automatic classification of tissue types of region of interest (ROI) plays an important role in computer-aided diagnosis. In the current study, we focus on the classification of three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor) in T1-weighted contrast-enhanced MRI (CE-MRI) images. Spatial pyramid matching (SPM), which splits the image into increasingly fine rectangular subregions and computes histograms of local features from each subregion, exhibits excellent results for natural scene classification. However, this approach is not applicable for brain tumors, because of the great variations in tumor shape and size. In this paper, we propose a method to enhance the classification performance. First, the augmented tumor region via image dilation is used as the ROI instead of the original tumor region because tumor surrounding tissues can also offer important clues for tumor types. Second, the augmented tumor region is split into increasingly fine ring-form subregions. We evaluate the efficacy of the proposed method on a large dataset with three feature extraction methods, namely, intensity histogram, gray level co-occurrence matrix (GLCM), and bag-of-words (BoW) model. Compared with using tumor region as ROI, using augmented tumor region as ROI improves the accuracies to 82.31% from 71.39%, 84.75% from 78.18%, and 88.19% from 83.54% for intensity histogram, GLCM, and BoW model, respectively. In addition to region augmentation, ring-form partition can further improve the accuracies up to 87.54%, 89.72%, and 91.28%. These experimental results demonstrate that the proposed method is feasible and effective for the classification of brain tumors in T1-weighted CE-MRI. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic value of symptom screening for tuberculosis (TB) case finding defined in National Tuberculosis Control Program in China (China NTP) among elderly people(≥65 years) and younger people(<65 years). Methods: We made a secondary analysis in a population-based TB prevalence survey in China in 2010. Questionnaire including information for cough and haemoptysis was completed by face to face interview, and then chest radiography was conducted in all eligible participants. Sputum smear and culture were followed for all TB suspects. We calculated the odds ratios (OR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under the receiver operating characteristic curve (AUC) of using different symptoms for screening to detect bacteriologically positive TB in subpopulations stratified by age 65, to evaluate the performance of symptom screening for TB. Findings: Of 315 newly diagnosed bacteriologically positive TB, 131 patients (41.59%) were elderly, and 48.57% of TB patients were asymptomatic. Nearly 50% patients did not present cough of any duration, and less than half present cough more than 2 weeks, a defined suspected symptom in China NTP. Cough of any duration was reported more in patients aged under 65 than those in elderly, especially for the acute cough (9.78% vs 6.87%). Those symptoms defined by China NTP were reported by less than half participants in two subpopulations. Acute cough (<2 weeks) was an independent predictor of TB in people aged under 65 (adjusted OR: 3.3, 95% CI: 2.0-5.5), but not in those aged 65 and above (adjusted OR: 1.4, 95% CI: 0.7-2.9). The specificity for each symptom was significantly higher in participants aged under 65 (P<0.01), and sensitivities of most symptoms were significantly higher among elderly (P<0.05 or P<0.01). When compared with cough for 2 weeks and more, using cough of any duration for symptom screening increased the sensitivity from 42.9% to 51. % for all participants, and the AUC increased from 0.70 to 0.74 for participants aged under 65 without significant difference. Conclusions: There is a high percent of asymptomatic TB patients, and those symptoms adopted in China NTP for screening is poorly predictive for TB. The presence of TB symptoms, the sensitivities and specificities of symptoms for TB were distinct between two subpopulations cut by age 65, implying different case finding strategies should be established for them. The current case finding strategy should be improved, and further studies should be done to evaluate the performance and cost-effectiveness of different symptom screening strategy. [ABSTRACT FROM AUTHOR]

Stem cells have remarkable self-renewal ability and differentiation potency, which are critical for tissue repair and tissue homeostasis. Recently it has been found, in many systems (e.g. gut, neurons, and hematopoietic stem cells), that the self-renewal and differentiation balance is maintained when the stem cells divide asymmetrically. Drosophila male germline stem cells (GSCs), one of the best characterized model systems with well-defined stem cell niches, were reported to divide asymmetrically, where centrosome plays an important role. Utilizing time-lapse live cell imaging, customized tracking, and image processing programs, we found that most acentrosomal GSCs have the spectrosomes reposition from the basal end (wild type) to the apical end close to hub-GSC interface (acentrosomal GSCs). In addition, these apically positioned spectrosomes were mostly stationary while the basally positioned spectrosomes were mobile. For acentrosomal GSCs, their mitotic spindles were still highly oriented and divided asymmetrically with longer mitosis duration, resulting in asymmetric divisions. Moreover, when the spectrosome was knocked out, the centrosomes velocity decreased and centrosomes located closer to hub-GSC interface. We propose that in male GSCs, the spectrosome recruited to the apical end plays a complimentary role in ensuring proper spindle orientation when centrosome function is compromised. [ABSTRACT FROM AUTHOR]

During acute kidney injury (AKI), tubular cell dedifferentiation initiates cell regeneration; hepatocyte growth factor (HGF) is involved in modulating cell dedifferentiation. Mesenchymal stem cell (MSC)-derived microvesicles (MVs) deliver RNA into injured tubular cells and alter their gene expression, thus regenerating these cells. We boldly speculated that MVs might induce HGF synthesis via RNA transfer, thereby facilitating tubular cell dedifferentiation and regeneration. In a rat model of unilateral AKI, the administration of MVs promoted kidney recovery. One of the mechanisms of action is the acceleration of tubular cell dedifferentiation and growth. Both in vivo and in vitro, rat HGF expression in damaged rat tubular cells was greatly enhanced by MV treatment. In addition, human HGF mRNA present in MVs was delivered into rat tubular cells and translated into the HGF protein as another mechanism of HGF induction. RNase treatment abrogated all MV effects. In the in vitro experimental setting, the conditioned medium of MV-treated injured tubular cells, which contains a higher concentration of HGF, strongly stimulated cell dedifferentiation and growth, as well as Erk1/2 signaling activation. Intriguingly, these effects were completely abrogated by either c-Met inhibitor or MEK inhibitor, suggesting that HGF induction is a crucial contributor to the acceleration of cell dedifferentiation and growth. All these findings indicate that MV-induced HGF synthesis in damaged tubular cells via RNA transfer facilitates cell dedifferentiation and growth, which are important regenerative mechanisms. [ABSTRACT FROM AUTHOR]

Tumor immunosurveillance is known to be of critical importance in controlling tumorigenesis and progression in various cancers. The role of gamma-interferon-inducible lysosomal thiol reductase (GILT) in tumor immunosurveillance has recently been studied in several malignant diseases, but its role in breast cancer remains to be elucidated. In the present study, we found GILT as a significant different expressed gene by cDNA microarray analysis. To further determine the role of GILT in breast cancer, we examined GILT expression in breast cancers as well as noncancerous breast tissues by immunohistochemistry and real-time PCR, and assessed its association with clinicopathologic characteristics and patient outcome. The absence of GILT expression increased significantly from 2.02% (2/99) in noncancerous breast tissues to 15.6% (34/218) in breast cancer tissues (P<0.001). In accordance with its proliferation inhibiting function, GILT expression was inversely correlated with Ki67 index (P<0.05). In addition, absence of GILT was positively correlated with adverse characteristics of breast cancers, such as histological type, tumor size, lymph nodes status, and pTNM stage (P<0.05). Consistently, breast cancers with reduced GILT expression had poorer disease-free survival (P<0.005). Moreover, significantly decreased expression of GILT was found in both primary and metastatic breast cancer cells, in contrast to normal epithelial cells. These findings indicate that GILT may act as a tumor suppressor in breast cancer, in line with its previously suggested role in anti-tumor immunity. Thus, GILT has the potential to be a novel independent prognostic factor in breast cancer and further studies are needed to illustrate the underlying mechanism of this relationship. [ABSTRACT FROM AUTHOR]

Background: Confocal laser endomicroscopy (CLE) can provide in vivo subcellular resolution images of esophageal lesions. However, the learning curve in interpreting CLE images of precancerous or early-stage esophageal squamous cancer is unknown. The goal of this study is to evaluate the diagnostic accuracy and inter-observer agreement for differentiating esophageal lesions in CLE images among experienced and inexperienced observers and to assess the learning curve. Method: After a short training, 8 experienced and 14 inexperienced endoscopists evaluated in sequence 4 sets of high-quality CLE images. Their diagnoses were corrected and discussed after each set. For each image, the diagnostic results, confidence in diagnosis, quality and time to evaluate were recorded. Results: Overall, diagnostic accuracy was greater for the second, third, fourth set of images as compared with the initial set (odds ratio [OR] 2.01, 95% CI 1.22–3.31; 7.95, 3.74–16.87; and 6.45, 3.14–13.27), respectively, with no difference between the third and fourth sets in accuracy (p = 0.67). Previous experience affected the diagnostic accuracy only in the first set of images (OR 3.70, 1.87–7.29, p<0.001). Inter-observer agreement was higher for experienced than inexperienced endoscopists (0.732 vs. 0.666, p<0.01) Conclusion: CLE is a promising technology that can be quickly learned after a short training period; previous experience is associated with diagnostic accuracy only at the initial stage of learning. [ABSTRACT FROM AUTHOR]

In our previous study, microvesicles (MVs) released from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) retard the growth of bladder cancer cells. We would like to know if MVs have a similar effect on human renal cell carcinoma (RCC). By use of cell culture and the BALB/c nu/nu mice xeno-graft model, the influence of MVs upon the growth and aggressiveness of RCC (786-0) was assessed. Cell counting kit-8 (CCK-8) assay, incidence of tumor, tumor size, Ki-67 or TUNEL staining was used to evaluate tumor cell growth in vitro or in vivo. Flow cytometry assay (in vitro) or examination of cyclin D1 expression (in vivo) was carried out to determine the alteration of cell cycle. The aggressiveness was analyzed by Wound Healing Assay (in vitro) or MMP-2 and MMP-9 expression (in vivo). AKT/p-AKT, ERK1/2/p-ERK1/2 or HGF/c-MET expression was detected by real-time PCR or western blot. Our data demonstrated that MVs promote the growth and aggressiveness of RCC both in vitro and in vivo. In addition, MVs facilitated the progression of cell cycle from G0/1 to S. HGF expression in RCC was greatly induced by MVs, associated with activation of AKT and ERK1/2 signaling pathways. RNase pre-treatment abrogated all effects of MVs. In summary, induction of HGF synthesis via RNA transferred by MVs activating AKT and ERK1/2 signaling is one of crucial contributors to the pro-tumor effect. [ABSTRACT FROM AUTHOR]

Posture segmentation plays an essential role in human motion analysis. The state-of-the-art method extracts sufficiently high-dimensional features from 3D depth images for each 3D point and learns an efficient body part classifier. However, high-dimensional features are memory-consuming and difficult to handle on large-scale training dataset. In this paper, we propose an efficient two-stage dimension reduction scheme, termed biview learning, to encode two independent views which are depth-difference features (DDF) and relative position features (RPF). Biview learning explores the complementary property of DDF and RPF, and uses two stages to learn a compact yet comprehensive low-dimensional feature space for posture segmentation. In the first stage, discriminative locality alignment (DLA) is applied to the high-dimensional DDF to learn a discriminative low-dimensional representation. In the second stage, canonical correlation analysis (CCA) is used to explore the complementary property of RPF and the dimensionality reduced DDF. Finally, we train a support vector machine (SVM) over the output of CCA. We carefully validate the effectiveness of DLA and CCA utilized in the two-stage scheme on our 3D human points cloud dataset. Experimental results show that the proposed biview learning scheme significantly outperforms the state-of-the-art method for human posture segmentation. [ABSTRACT FROM AUTHOR]

Objective: To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to determine how to stage liver fibrosis with spleen DCE-MRI parameters. Materials and Methods: Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP), positive enhancement integral (PEI), maximum slope of increase (MSI) and maximum slope of decrease (MSD) of spleen were measured, and statistically analyzed to stage this disease. Results: Spearman's rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P<0.001), and that PEI tended to decrease from stage 0 to 4 (r = −0.709, P<0.001). MSD increased slightly from stage 0 to 2 (P>0.05), and decreased from stage 2 to 4 (P<0.05). MSI increased from stage 0 to 1, and decreased from stage 1 to 4 (all P>0.05). Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1–4, between 0–1 and 2–4, between 0–2 and 3–4, or between 0–3 and 4 (all P<0.01). MSD could discriminate between 0–2 and 3–4 (P = 0.006), or between 0–3 and 4 (P = 0.012). MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC) of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively). PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively). Conclusion: Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages. [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). In addition to GARS, mutations in three other tRNA synthetase genes cause similar neuropathies, although the underlying mechanisms are not fully understood. To address this, we generated transgenic mice that ubiquitously over-express wild-type GARS and crossed them to two dominant mouse models of CMT2D to distinguish loss-of-function and gain-of-function mechanisms. Over-expression of wild-type GARS does not improve the neuropathy phenotype in heterozygous Gars mutant mice, as determined by histological, functional, and behavioral tests. Transgenic GARS is able to rescue a pathological point mutation as a homozygote or in complementation tests with a Gars null allele, demonstrating the functionality of the transgene and revealing a recessive loss-of-function component of the point mutation. Missense mutations as transgene-rescued homozygotes or compound heterozygotes have a more severe neuropathy than heterozygotes, indicating that increased dosage of the disease-causing alleles results in a more severe neurological phenotype, even in the presence of a wild-type transgene. We conclude that, although missense mutations of Gars may cause some loss of function, the dominant neuropathy phenotype observed in mice is caused by a dose-dependent gain of function that is not mitigated by over-expression of functional wild-type protein. [ABSTRACT FROM AUTHOR]

Background and Methods: To understand the burden and epidemiology of Streptococcus pneumoniae disease among children between 1 and 59 months of age in China, we conducted a review of literature published between 1980 and 2008 applying standardized algorithms. Because of the absence of population-based surveillance for pneumococcal disease (PD), we identified all-cause pneumonia, bacteremia and meningitis burden, syndromes most commonly associated with S. pneumoniae, and applied the proportion of disease attributable to S. pneumoniae from studies that determined the etiology of these three syndromes to calculate PD burden. Because of the microbiologic difficulties in identifying S. pneumoniae-attributable pneumonia which likely underestimates the pneumonia burden, we also used the proportion obtained from vaccine efficacy trials. Results: Between 1980 and 2008, there were 12,815 cases/100,000/year of all-cause pneumonia among children between 1 month and 59 months, with 526 deaths/100,000 annually. There were 14 meningitis cases/100,000/year. We estimate that as of 2000, there were 260,768 (113,000 to 582,382) and 902 (114-4,463) cases of pneumococcal pneumonia and meningitis, respectively with 10,703 (4,638-23,904) and 75 (9-370) pneumococcal pneumonia and meningitis deaths, respectively. Pneumococcal pneumonia cases and deaths were more than two-fold higher, 695,382 (173,845-1,216,918) and 28,542 (7,136-49,949), respectively, when parameters from efficacy trials were used. Serotypes 19F, 19A and 14 were the most common serotypes obtained from pneumonia/meningitis patients. Currently available vaccines are expected to cover 79.5% to 88.4% of the prevalent serotypes. With high antibiotic resistance, introducing pneumococcal vaccines to the routine immunization program should be considered in China. Population-based studies are warranted. [ABSTRACT FROM AUTHOR]

Objectives:China is one of the 22 tuberculosis (TB) high-burden countries in the world. As TB is a major public health problem in China, spatial analysis could be applied to detect geographic distribution of TB clusters for targeted intervention on TB epidemics. Methods:Spatial analysis was applied for detecting TB clusters on county-based TB notification data in the national notifiable infectious disease case reporting surveillance system from 2005 to 2011. Two indicators of TB epidemic were used including new sputum smear-positive (SS+) notification rate and total TB notification rate. Global Moran’s I by ArcGIS was used to assess whether TB clustering and its trend were significant. SaTScan software that used the retrospective space-time analysis and Possion probability model was utilized to identify geographic areas and time period of potential clusters with notification rates on county-level from 2005 to 2011. Results:Two indicators of TB notification had presented significant spatial autocorrelation globally each year (p<0.01). Global Moran’s I of total TB notification rate had positive trend as time went by (t=6.87, p<0.01). The most likely clusters of two indicators had similar spatial distribution and size in the south-central regions of China from 2006 to 2008, and the secondary clusters in two regions: northeastern China and western China. Besides, the secondary clusters of total TB notification rate had two more large clustering centers in Inner Mongolia, Gansu and Qinghai provinces and several smaller clusters in Shanxi, Henan, Hebei and Jiangsu provinces. Conclusion:The total TB notification cases clustered significantly in some special areas each year and the clusters trended to aggregate with time. The most-likely and secondary clusters that overlapped among two TB indicators had higher TB burden and risks of TB transmission. These were the focused geographic areas where TB control efforts should be prioritized. [ABSTRACT FROM AUTHOR]

The HIF1- and HIF2-mediated transcriptional responses play critical roles in solid tumor progression. Despite significant similarities, including their binding to promoters of both HIF1 and HIF2 target genes, HIF1 and HIF2 proteins activate unique subsets of target genes under hypoxia. The mechanism for HIF target gene specificity has remained unclear. Using siRNA or inhibitor, we previously reported that STAT3 or USF2 is specifically required for activation of endogenous HIF1 or HIF2 target genes. In this study, using reporter gene assays and chromatin immuno-precipitation, we find that STAT3 or USF2 exhibits specific binding to the promoters of HIF1 or HIF2 target genes respectively even when over-expressed. Functionally, HIF1α interacts with STAT3 to activate HIF1 target gene promoters in a HIF1α HLH/PAS and N-TAD dependent manner while HIF2α interacts with USF2 to activate HIF2 target gene promoters in a HIF2α N-TAD dependent manner. Physically, HIF1α HLH and PAS domains are required for its interaction with STAT3 while both N- and C-TADs of HIF2α are involved in physical interaction with USF2. Importantly, addition of functional USF2 binding sites into a HIF1 target gene promoter increases the basal activity of the promoter as well as its response to HIF2+USF2 activation while replacing HIF binding site with HBS from a HIF2 target gene does not change the specificity of the reporter gene. Importantly, RNA Pol II on HIF1 or HIF2 target genes is primarily associated with HIF1α or HIF2α in a STAT3 or USF2 dependent manner. Thus, we demonstrate here for the first time that HIF target gene specificity is achieved by HIF transcription partners that are required for HIF target gene activation, exhibit specific binding to the promoters of HIF1 or HIF2 target genes and selectively interact with HIF1α or HIF2α protein. [ABSTRACT FROM AUTHOR]

Transformation is the main platform for genetic improvement and gene function studies in plants. However, the established somatic embryo transformation system for grapevines is time-consuming and has low efficiency, which limits its utilization in functional genomics research. Vitis amurensis is a wild Vitis species with remarkable cold tolerance. The lack of an efficient genetic transformation system for it has significantly hindered the functional identification of cold stress related genes in the species. Herein, an efficient method was established to produce transformed calli of V. amurensis. Segments of petioles from micropropagated plantlets of V. amurensis exhibited better capacity to differentiate calli than leaf-discs and stem segments, and thus was chosen as target tissue for Agrobacterium-mediated transformation. Both neomycin phosphotransferase II (NPTII) and enhanced green fluorescent protein (eGFP) genes were used for simultaneous selection of transgenic calli based on kanamycin resistance and eGFP fluorescence. Several parameters affecting the transformation efficiency were optimized including the concentration of kanamycin, Agrobacterium stains, bacterial densities, infection treatments and co-cultivation time. The transgenic callus lines were verified by checking the integration of NPTII gene into calli genomes, the expression of eGFP gene and the fluorescence of eGFP. Up to 20% of the petiole segments produced transformed calli after 2 months of cultivation. This efficient transformation system will facilitate the functional analysis of agronomic characteristics and related genes not only in V. amurensis but also in other grapevine species.

Starch is one of the major components of cereals, tubers, and fruits. Genes encoding granule-bound starch synthase (GBSS), which is responsible for amylose synthesis, have been extensively studied in cereals but little is known about them in fruits. Due to their low copy gene number, GBSS genes have been used to study plant phylogenetic and evolutionary relationships. In this study, GBSS genes have been isolated and characterized in three fruit trees, including apple, peach, and orange. Moreover, a comprehensive evolutionary study of GBSS genes has also been conducted between both monocots and eudicots. Results have revealed that genomic structures of GBSS genes in plants are conserved, suggesting they all have evolved from a common ancestor. In addition, the GBSS gene in an ancestral angiosperm must have undergone genome duplication ∼251 million years ago (MYA) to generate two families, GBSSI and GBSSII. Both GBSSI and GBSSII are found in monocots; however, GBSSI is absent in eudicots. The ancestral GBSSII must have undergone further divergence when monocots and eudicots split ∼165 MYA. This is consistent with expression profiles of GBSS genes, wherein these profiles are more similar to those of GBSSII in eudicots than to those of GBSSI genes in monocots. In dicots, GBSSII must have undergone further divergence when rosids and asterids split from each other ∼126 MYA. Taken together, these findings suggest that it is GBSSII rather than GBSSI of monocots that have orthologous relationships with GBSS genes of eudicots. Moreover, diversification of GBSS genes is mainly associated with genome-wide duplication events throughout the evolutionary course of history of monocots and eudicots.

Background and Methods: To understand the burden and epidemiology of Streptococcus pneumoniae disease among children between 1 and 59 months of age in China, we conducted a review of literature published between 1980 and 2008 applying standardized algorithms. Because of the absence of population-based surveillance for pneumococcal disease (PD), we identified all-cause pneumonia, bacteremia and meningitis burden, syndromes most commonly associated with S. pneumoniae, and applied the proportion of disease attributable to S. pneumoniae from studies that determined the etiology of these three syndromes to calculate PD burden. Because of the microbiologic difficulties in identifying S. pneumoniae-attributable pneumonia which likely underestimates the pneumonia burden, we also used the proportion obtained from vaccine efficacy trials., Results: Between 1980 and 2008, there were 12,815 cases/100,000/year of all-cause pneumonia among children between 1 month and 59 months, with 526 deaths/100,000 annually. There were 14 meningitis cases/100,000/year. We estimate that as of 2000, there were 260,768 (113,000 to 582,382) and 902 (114-4,463) cases of pneumococcal pneumonia and meningitis, respectively with 10,703 (4,638-23,904) and 75 (9-370) pneumococcal pneumonia and meningitis deaths, respectively. Pneumococcal pneumonia cases and deaths were more than two-fold higher, 695,382 (173,845-1,216,918) and 28,542 (7,136-49,949), respectively, when parameters from efficacy trials were used. Serotypes 19F, 19A and 14 were the most common serotypes obtained from pneumonia/meningitis patients. Currently available vaccines are expected to cover 79.5% to 88.4% of the prevalent serotypes. With high antibiotic resistance, introducing pneumococcal vaccines to the routine immunization program should be considered in China. Population-based studies are warranted.