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1.  Establishment of a Simple and Quick Method for Detecting Extended-Spectrum β-Lactamase (ESBL) Genes in Bacteria 
Extended-spectrum β-lactamase (ESBL) genes that render bacteria resistant to antibiotics are commonly detected using phenotype testing, which is time consuming and not sufficiently accurate. To establish a better method, we used phenotype testing to identify ESBL-positive bacterial strains and conducted PCR to screen for TEM (named after the patient Temoneira who provided the first sample), sulfhydryl reagent variable (SHV), cefotaxime (CTX)-M-1, and CTX-M-9, the 4 most common ESBL types and subtypes. We then performed multiplex PCR with 1 primer containing a biotin and hybridized the PCR products with gene-specific probes that were coupled with microbeads and coated with a specific fluorescence. The hybrids were linked to streptavidin-R-phycoerythrins (SA-PEs) and run through a flow cytometer, which sorted the fluorescently dyed microbeads and quantified the PEs. The results from single PCR, multiplex PCR, and cytometry were consistent with each other. We used this method to test 169 clinical specimens that had been determined for phenotypes and found 154 positive for genotypes, including 30 of the 45 samples that were negative for phenotypes. The CTX-M genotype tests alone, counting both positive and negative cases, showed 99.41% (168/169) consistency with the ESBL phenotype test. Thus, we have established a multiplex-PCR system as a simple and quick method that is high throughput and accurate for detecting 4 common ESBL types and subtypes.
doi:10.7171/jbt.16-2704-001
PMCID: PMC5026501  PMID: 27672351
multiplex PCR; flow fluorescence; drug-resistance gene; antibiotics
3.  Comparison of the efficacy and feasibility of en bloc transurethral resection of bladder tumor versus conventional transurethral resection of bladder tumor 
Medicine  2016;95(45):e5372.
Abstract
Background:
The aim of this meta-analysis was to compare the feasibility of en bloc transurethral resection of bladder tumor (ETURBT) versus conventional transurethral resection of bladder tumor (CTURBT).
Methods:
Relevant trials were identified in a literature search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Google Scholar using appropriate search terms. All comparative studies reporting participant demographics, tumor characteristics, study characteristics, and outcome data were included.
Results:
Seven trials with 886 participants were included, 438 underwent ETURBT and 448 underwent CTURBT. There was no significant difference in operation time between 2 groups (P = 0.38). The hospitalization time (HT) and catheterization time (CT) were shorter in ETURBT group (mean difference[MD] −1.22, 95% confidence interval [CI] −1.63 to −0.80, P < 0.01; MD −0.61, 95% CI −1.11 to −0.11, P < 0.01). There was significant difference in 24-month recurrence rate (24-month RR) (odds ratio [OR] 0.66, 95% CI 0.47–0.92, P = 0.02). The rate of complication with respect to bladder perforation (P = 0.004), bladder irritation (P < 0.01), and obturator nerve reflex (P < 0.01) was lower in ETURBT. The postoperative adjuvant intravesical chemotherapy was evaluated by subgroup analysis, and 24-month RR in CTURBT is higher than that in ETURBT in mitomycin intravesical irrigation group (P = 0.02).
Conclusion:
The first meta-analysis indicates that ETURBT might prove to be preferable alternative to CTURBT management of nonmuscle invasive bladder carcinoma. ETURBT is associated with shorter HT and CT, less complication rate, and lower recurrence-free rate. Moreover, it can provide high-qualified specimen for the pathologic diagnosis. Well designed randomized controlled trials are needed to make results comparable.
doi:10.1097/MD.0000000000005372
PMCID: PMC5106070  PMID: 27828864
bladder tumor; CTURBT; en bloc; ETURBT; transurethral
4.  The Mutation of Glu at Amino Acid 3838 of AtMDN1 Provokes Pleiotropic Developmental Phenotypes in Arabidopsis 
Scientific Reports  2016;6:36446.
MDN1/Rea1, as an AAA-type ATPase, is predicted to be the largest protein involved in pre-ribosome maturation in most organisms. However, its function in plant growth and development is poorly understood. Here, we characterized a novel Arabidopsis mutant, dwarf & short root (dsr) 1, which shows pleiotropic developmental phenotypes, such as slow germination, short root, dwarf shoot, and reduced seed set under normal growth conditions. Using positional cloning, we revealed that the AtMDN1 function is impaired by a ‘glutamic acid’ to ‘lysine’ change at position 3838 of the amino acid sequence in dsr1. Multiple sequence alignment analysis revealed that the mutated Glu residue, which located in the linker domain of AtMDN1, is extremely conserved among organisms. AtMDN1 is expressed in various tissues, particularly in the shoot apex and root tip. Moreover, the results of transcript profile analyses showed that the dysfunction of AtMDN1 in dsr1 impairs the expression of genes related to plant growth and development, which is tightly associated with the pleiotropic phenotypes of dsr1. Thus, we concluded that the Glu residue plays a vital role in maintaining AtMDN1 functions, which are essential for plant growth and development.
doi:10.1038/srep36446
PMCID: PMC5099923  PMID: 27824150
5.  DAMPs, Ageing, and Cancer: The ‘DAMP Hypothesis’ 
Ageing research reviews  2014;24(0 0):3-16.
Ageing is a complex and multifactorial process characterized by the accumulation of many forms of damage at the molecular, cellular, and tissue level with advancing age. Ageing increases the risk of the onset of chronic inflammation-associated diseases such as cancer, diabetes, stroke, and neurodegenerative disease. In particular, ageing and cancer share some common origins and hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury, reprogrammed metabolism, and degradation system impairment (including within the ubiquitin-proteasome system and the autophagic machinery). Recent advances indicate that damage-associated molecular pattern molecules (DAMPs) such as high mobility group box 1, histones, S100, and heat shock proteins play location-dependent roles inside and outside the cell. These provide interaction platforms at molecular levels linked to common hallmarks of ageing and cancer. They can act as inducers, sensors, and mediators of stress through individual plasma membrane receptors, intracellular recognition receptors (e.g., advanced glycosylation end product-specific receptors, AIM2-like receptors, RIG-I-like receptors, and NOD1-like receptors, and toll-like receptors), or following endocytic uptake. Thus, the DAMP Hypothesis is novel and complements other theories that explain the features of ageing. DAMPs represent ideal biomarkers of ageing and provide an attractive target for interventions in ageing and age-associated diseases.
doi:10.1016/j.arr.2014.10.004
PMCID: PMC4416066  PMID: 25446804
ageing; cancer; longevity; damage-associated molecular pattern (DAMP) molecules; receptor; biomarker
6.  Frailty in Older Adults: A Nationally Representative Profile in the United States 
Background.
Frailty assessment provides a means of identifying older adults most vulnerable to adverse outcomes. Attention to frailty in clinical practice is more likely with better understanding of its prevalence and associations with patient characteristics. We sought to provide national estimates of frailty in older people.
Methods.
A popular, validated frailty phenotype proposed by Fried and colleagues was applied to 7,439 participants in the 2011 baseline of the National Health and Aging Trends Study, a national longitudinal study of persons aged 65 and older. All measures drew on a 2-hour in-person interview. Weighted estimates of frailty prevalence were obtained.
Results.
Fifteen percent (95% CI: 14%, 16%) of the older non-nursing home population is frail, and 45% is prefrail (95% CI: 44%, 47%). Frailty is more prevalent at older ages, among women, racial and ethnic minorities, those in supportive residential settings, and persons of lower income. Independently of these characteristics, frailty prevalence varies substantially across geographic regions. Chronic disease and disability prevalence increase steeply with frailty. Among the frail, 42% were hospitalized in the previous year, compared to 22% of the prefrail and 11% of persons considered robust. Hip, back, and heart surgery in the last year were associated with frailty. Over half of frail persons had a fall in the previous year.
Conclusions.
Our findings support the importance of frailty in late-life health etiology and potential value of frailty as a marker of risk for adverse health outcomes and as a means of identifying opportunities for intervention in clinical practice and public health policy.
doi:10.1093/gerona/glv133
PMCID: PMC4723664  PMID: 26297656
Epidemiology; Health disparities; Public health
7.  Positive Aspects of Family Caregiving for Dementia: Differential Item Functioning by Race 
Objectives.
Due to increasing interest in the positive experiences associated with family caregiving, potential demographic group differences were examined on the Positive Aspects of Caregiving (PAC) scale at both the item and scale levels.
Method.
Family caregivers (N = 642) completed the PAC as part of their participation in the Resources for Enhancing Alzheimer’s Caregiver Health (REACH II) clinical trial. Multiple indicators, multiple causes models were used to examine potential differential item functioning (DIF) across demographic subgroups.
Results.
Overall PAC scale scores indicated that both Hispanics and African Americans experienced more PAC than Whites. Two items with statistically significant (p < .004) and practically meaningful (odds ratio > 2.0) DIF were found for African American caregivers. After controlling for the underlying unidimensional construct, African Americans reported that caregiving gave them “a more positive attitude toward life” and enabled them to “appreciate life more” than either Whites or Hispanics. No instances of meaningful DIF were found between Hispanics and Whites, women and men, or spouses and nonspouses.
Discussion.
PAC scores differ significantly by race. In addition, 2 items with meaningful race DIF identify content areas that are particularly relevant to the cultural experiences of African American caregivers.
doi:10.1093/geronb/gbv034
PMCID: PMC4841161  PMID: 26033356
Caregiving; Dementia; Differential item functioning (DIF); Measurement; Minority and diverse populations
8.  Breastfeeding and child development outcomes: an investigation of the nurturing hypothesis 
Maternal & child nutrition  2015;12(4):757-767.
This study investigated whether the nurturing hypothesis – that breastfeeding serves as a proxy for family socio-economic characteristics and parenting behaviours – accounts for the association of breastfeeding with children’s academic abilities. Data used were from the Child Development Supplement of the Panel Study of Income Dynamics, which followed up a cohort of 3563 children aged 0–12 in 1997. Structural equation modelling simultaneously regressed outcome variables, including three test scores of academic ability and two subscales of behaviour problems, on the presence and duration of breastfeeding, family socio-economic characteristics, parenting behaviours and covariates. Breastfeeding was strongly related to all three tests scores but had no relationships with behaviour problems. The adjusted mean differences in the Letter–Word Identification, Passage Comprehension) and Applied Problems test scores between breastfed and non-breastfed children were 5.14 [95% confidence interval (CI): 3.14, 7.14], 3.46 (95% CI: 1.67, 5.26) and 4.24 (95% CI: 2.43, 6.04), respectively. Both socio-economic characteristics and parenting behaviours were related to higher academic test scores and were associated with a lower prevalence of externalising and internalising behaviour problems. The associations of breastfeeding with behaviour problems are divergent from those of socio-economic characteristics and parenting behaviours. The divergence suggests that breastfeeding may not be a proxy of socio-economic characteristics and parenting behaviours, as proposed by the nurturing hypothesis. The mechanism of breastfeeding benefits is likely to be different from those by which family socio-economic background and parenting practices exert their effects. Greater clarity in understanding the mechanisms behind breastfeeding benefits will facilitate the development of policies and programs that maximise breastfeeding’s impact.
doi:10.1111/mcn.12200
PMCID: PMC5087141  PMID: 26194444
academic ability; breastfeeding; behaviour problems; child development
9.  The influence factors of medical professionalism 
Medicine  2016;95(43):e5128.
Supplemental Digital Content is available in the text
Abstract
As the relationship between physicians and patients deteriorated in China recently, medical conflicts occurred more frequently now. Physicians, to a certain extent, also take some responsibilities. Awareness of medical professionalism and its influence factors can be helpful to take targeted measures and alleviate the contradiction. Through a combination of physicians’ self-assessment and patients’ assessment in ambulatory care clinics in Chengdu, this research aims to evaluate the importance of medical professionalism in hospitals and explore the influence factors, hoping to provide decision-making references to improve this grim situation. From February to March, 2013, a cross-sectional study was conducted in 2 tier 3 hospitals, 5 tier 2 hospitals, and 10 community hospitals through a stratified-random sampling method on physicians and patients, at a ratio of 1/5. Questionnaires are adopted from a pilot study. A total of 382 physicians and 1910 patients were matched and surveyed. Regarding the medical professionalism, the scores of the self-assessment for physicians were 85.18 ± 7.267 out of 100 and the scores of patient-assessment were 57.66 ± 7.043 out of 70. The influence factors of self-assessment were physicians’ working years (P = 0.003) and patients’ complaints (P = 0.006), whereas the influence factors of patient-assessment were patients’ ages (P = 0.001) and their physicians’ working years (P < 0.01) and satisfaction on the payment mode (P = 0.006). Higher self-assessment on the medical professionalism was in accordance with physicians of more working years and no complaint history. Higher patient-assessment was in line with elder patients, the physicians’ more working years, and higher satisfaction on the payment mode. Elder patients, encountering with physicians who worked more years in health care services or with higher satisfaction on the payment mode, contribute to higher scores in patient assessment part. The government should strengthen the medical professionalism for young physicians and improve the payment mode.
doi:10.1097/MD.0000000000005128
PMCID: PMC5089095  PMID: 27787366
medical professionalism; payment; satisfaction
10.  Real-time colorimetric detection of DNA methylation of the PAX1 gene in cervical scrapings for cervical cancer screening with thiol-labeled PCR primers and gold nanoparticles 
Background
DNA methylation can induce carcinogenesis by silencing key tumor suppressor genes. Analysis of aberrant methylation of tumor suppressor genes can be used as a prognostic and predictive biomarker for cancer. In this study, we propose a colorimetric method for the detection of DNA methylation of the paired box gene 1 (PAX1) gene in cervical scrapings obtained from 42 patients who underwent cervical colposcopic biopsy.
Methods
A thiolated methylation-specific polymerase chain reaction (MSP) primer was used to generate MSP products labeled with the thiol group at one end. After bisulfite conversion and MSP amplification, the unmodified gold nanoparticles (AuNPs) were placed in a reaction tube and NaCl was added to induce aggregation of bare AuNPs without generating polymerase chain reaction products. After salt addition, the color of AuNPs remained red in the methylated PAX1 gene samples because of binding to the MSP-amplified products. By contrast, the color of the AuNP colloid solution changed from red to blue in the non-methylated PAX1 gene samples because of aggregation of AuNPs in the absence of the MSP-amplified products. Furthermore, PAX1 methylation was quantitatively detected in cervical scrapings of patients with varied pathological degrees of cervical cancer. Conventional quantitative MSP (qMSP) was also performed for comparison.
Results
The two methods showed a significant correlation of the methylation frequency of the PAX1 gene in cervical scrapings with severity of cervical cancer (n=42, P<0.05). The results of the proposed method showed that the areas under the receiver operating characteristic curve (AUCs) of PAX1 were 0.833, 0.742, and 0.739 for the detection of cervical intraepithelial neoplasms grade 2 and worse lesions (CIN2+), cervical intraepithelial neoplasms grade 3 and worse lesions (CIN3+), and squamous cell carcinoma, respectively. The sensitivity and specificity for detecting CIN2+ lesions were 0.941 and 0.600, respectively, with a cutoff value of 31.27%. The proposed method also showed superior sensitivity over qMSP methods for the detection of CIN2+ and CIN3+ (0.941 vs 0.824 and 1.000 vs 0.800, respectively). Furthermore, the novel method exhibited higher AUC (0.833) for the detection of CIN2+ than qMSP (0.807).
Conclusion
The results of thiol-labeled AuNP method were clearly observed by the naked eyes without requiring any expensive equipment. Therefore, the thiol-labeled AuNP method could be a simple but efficient strategy for cervical cancer screening.
doi:10.2147/IJN.S116288
PMCID: PMC5068476  PMID: 27789946
colorimetric detection; gold nanoparticles; DNA methylation; cervical cancer screening; UV-vis; high sensitivity; quantitative detection
11.  Overexpression of RACK1 Promotes Metastasis by Enhancing Epithelial-Mesenchymal Transition and Predicts Poor Prognosis in Human Glioma 
Emerging studies show that dysregulation of the receptor of activated protein kinase C1 (RACK1) plays a crucial role in tumorigenesis and progression of various cancers. However, the biological function and underlying mechanism of RACK1 in glioma remains poorly defined. Here, we found that RACK1 was significantly up-regulated in glioma tissues compared with normal brain tissues, being closely related to clinical stage of glioma both in mRNA and protein levels. Moreover, Kaplan-Meier analysis demonstrated that patients with high RACK1 expression had a poor prognosis (p = 0.0062, HR = 1.898, 95% CI: 1.225–3.203). In vitro functional assays indicated that silencing of RACK1 could dramatically promote apoptosis and inhibit cell proliferation, migration, and invasion of glioma cells. More importantly, knockdown of RACK1 led to a vast accumulation of cells in G0/G1 phase and their reduced proportions at the S phase by suppressing the expression of G1/S transition key regulators Cyclin D1 and CDK6. Additionally, this forced down-regulation of RACK1 significantly suppressed migration and invasion via inhibiting the epithelial-mesenchymal transition (EMT) markers, such as MMP2, MMP9, ZEB1, N-Cadherin, and Integrin-β1. Collectively, our study revealed that RACK1 might act as a valuable prognostic biomarker and potential therapeutic target for glioma.
doi:10.3390/ijerph13101021
PMCID: PMC5086760  PMID: 27763568
RACK1; cell cycle; epithelial-mesenchymal transition; prognosis
12.  Two-ligand priming mechanism for potentiated phosphoinositide synthesis is an evolutionarily conserved feature of Sec14-like phosphatidylinositol and phosphatidylcholine exchange proteins 
Molecular Biology of the Cell  2016;27(14):2317-2330.
The two-ligand priming mechanism for stimulated phosphoinositide synthesis described for Saccharomyces Sec14 is also a conserved feature of Sec14-like phosphatidylinositol- and phosphatidylcholine-transfer proteins of the most evolutionarily advanced plants.
Lipid signaling, particularly phosphoinositide signaling, plays a key role in regulating the extreme polarized membrane growth that drives root hair development in plants. The Arabidopsis AtSFH1 gene encodes a two-domain protein with an amino-terminal Sec14-like phosphatidylinositol transfer protein (PITP) domain linked to a carboxy-terminal nodulin domain. AtSfh1 is critical for promoting the spatially highly organized phosphatidylinositol-4,5-bisphosphate signaling program required for establishment and maintenance of polarized root hair growth. Here we demonstrate that, like the yeast Sec14, the AtSfh1 PITP domain requires both its phosphatidylinositol (PtdIns)- and phosphatidylcholine (PtdCho)-binding properties to stimulate PtdIns-4-phosphate [PtdIns(4)P] synthesis. Moreover, we show that both phospholipid-binding activities are essential for AtSfh1 activity in supporting polarized root hair growth. Finally, we report genetic and biochemical evidence that the two-ligand mechanism for potentiation of PtdIns 4-OH kinase activity is a broadly conserved feature of plant Sec14-nodulin proteins, and that this strategy appeared only late in plant evolution. Taken together, the data indicate that the PtdIns/PtdCho-exchange mechanism for stimulated PtdIns(4)P synthesis either arose independently during evolution in yeast and in higher plants, or a suitable genetic module was introduced to higher plants from a fungal source and subsequently exploited by them.
doi:10.1091/mbc.E16-04-0221
PMCID: PMC4945147  PMID: 27193303
13.  Comparative genomic, transcriptomic and secretomic profiling of Penicillium oxalicum HP7-1 and its cellulase and xylanase hyper-producing mutant EU2106, and identification of two novel regulatory genes of cellulase and xylanase gene expression 
Background
The filamentous fungus Penicillium oxalicum is a potential alternative to Trichoderma reesei for industrial production of a complete cellulolytic enzyme system for a bio-refinery. Comparative omics approaches can support rational genetic engineering and/or breeding of filamentous fungi with improved cellulase production capacity. In this study, comparative genomic, transcriptomic and secretomic profiling of P. oxalicum HP7-1 and its cellulase and xylanase hyper-producing mutant EU2106 were employed to screen for novel regulators of cellulase and xylanase gene expression.
Results
The 30.62 Mb P. oxalicum HP7-1 genome was sequenced, and 9834 protein-coding genes were annotated. Re-sequencing of the mutant EU2106 genome identified 274 single nucleotide variations and 12 insertion/deletions. Comparative genomic, transcriptomic and secretomic profiling of HP7-1 and EU2106 revealed four candidate regulators of cellulase and xylanase gene expression. Deletion of these candidate genes and measurement of the enzymatic activity of the resultant mutants confirmed the identity of three regulatory genes. POX02484 and POX08522, encoding a putative Zn(II)2Cys6 DNA-binding domain and forkhead protein, respectively, were found to be novel, while PoxClrB is an ortholog of ClrB, a key transcriptional regulator of cellulolytic enzyme gene expression in filamentous fungi. ΔPOX02484 and ΔPOX08522 mutants exhibited significantly reduced β-glucosidase activity, increased carboxymethylcellulose cellulase and xylanase activities, and altered transcription level of cellulase and xylanase genes compared with the parent strain ΔPoxKu70, with Avicel as the sole carbon source.
Conclusions
Two novel genes, POX02484 and POX08522, were found and characterized to regulate the expression of cellulase and xylanase genes in P. oxalicum. These findings are important for engineering filamentous fungi to improve cellulase and xylanase production.
Electronic supplementary material
The online version of this article (doi:10.1186/s13068-016-0616-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s13068-016-0616-9
PMCID: PMC5035457  PMID: 27688806
Penicillium oxalicum; Genomics; Transcriptomics; Secretomics; Transcription factor; Cellulase; Xylanase; Regulation
14.  Establishment of a Simple and Quick Method for Detecting Extended-Spectrum β-Lactamase (ESBL) Genes in Bacteria 
Extended-spectrum β-lactamase (ESBL) genes that render bacteria resistant to antibiotics are commonly detected using phenotype testing, which is time consuming and not sufficiently accurate. To establish a better method, we used phenotype testing to identify ESBL-positive bacterial strains and conducted PCR to screen for TEM (named after the patient Temoneira who provided the first sample), sulfhydryl reagent variable (SHV), cefotaxime (CTX)-M-1, and CTX-M-9, the 4 most common ESBL types and subtypes. We then performed multiplex PCR with 1 primer containing a biotin and hybridized the PCR products with gene-specific probes that were coupled with microbeads and coated with a specific fluorescence. The hybrids were linked to streptavidin-R-phycoerythrins (SA-PEs) and run through a flow cytometer, which sorted the fluorescently dyed microbeads and quantified the PEs. The results from single PCR, multiplex PCR, and cytometry were consistent with each other. We used this method to test 169 clinical specimens that had been determined for phenotypes and found 154 positive for genotypes, including 30 of the 45 samples that were negative for phenotypes. The CTX-M genotype tests alone, counting both positive and negative cases, showed 99.41% (168/169) consistency with the ESBL phenotype test. Thus, we have established a multiplex-PCR system as a simple and quick method that is high throughput and accurate for detecting 4 common ESBL types and subtypes.
doi:10.7171/jbt.16-2704-001
PMCID: PMC5026501  PMID: 27672351
multiplex PCR; flow fluorescence; drug-resistance gene; antibiotics
15.  An APOC3 3′UTR variant associated with plasma triglycerides levels and coronary heart disease by creating a functional miR-4271 binding site 
Scientific Reports  2016;6:32700.
Apolipoprotein C-III (APOC3) is a key regulator of plasma triglycerides levels. Increasing evidence has shown that loss-of-function mutations in APOC3 is associated with reduction in plasma triglycerides levels and will confer a benefit in patients at high risk for cardiovascular disease. However, these favorable mutations were extremely distribution discrepant among different ethnics. In this study, the APOC3 gene was resequenced and we identified a common variant which located in the microRNA-binding site in APOC3 and would affect its expression and the risk of coronary heart disease (CHD). The molecular mechanism was explored. We found that the T allele of rs4225 suppressed APOC3 translation by facilitating miR-4271 binding, but not the G allele. Subjects carrying the GG genotype had higher plasma APOC3 levels (p for trend = 0.03) than those with the TT genotype. Furthermore, the T allele was significantly associated with decreased triglyceride levels [Beta (SE): −0.024 (0.020), P = 0.03]. Finally, the case-control study suggested that the TT genotype resulted in a significant reduction in overall CHD risk [OR, 0.89 (95% confidence interval, 0.77–0.98), P = 0.009]. In conclusion, our results provide evidence that the rs4225 in the 3′-UTR of APOC3 might contribute to the risk of CHD by interfering with miR-4271 binding.
doi:10.1038/srep32700
PMCID: PMC5021972  PMID: 27624799
16.  Prognostic value of preoperative serum lactate dehydrogenase in thymic carcinoma 
Journal of Thoracic Disease  2016;8(9):2464-2472.
Background
The prognostic value of serum lactate dehydrogenase (LDH) has been demonstrated in various solid tumors. We attempted to determine whether serum LDH was predictive of survival in thymic carcinoma after surgical resection.
Methods
Ninety-five patients with thymic carcinoma treated in our hospital between January 2005 and December 2015 were retrospectively enrolled. Serum LDH was measured before surgery and categorized as low or high relative to the upper limit of normal (ULN) (225 U/L). The relationships of serum LDH level and other clinical variables with survival were estimated by Cox regression and Kaplan-Meier survival analysis.
Results
Serum LDH levels were found to be significantly associated with overall survival (OS) and progression-free survival (PFS) of these patients. The 1-, 3-, and 5-year PFS were 76%, 51%, and 38%, and the 1-, 3- and 5-year OS were 97%, 75%, and 46%, respectively. Univariate analysis found that high serum LDH (>225 U/L) was associated with both lower OS [hazard ratio (HR) =2.710; 95% confidence interval (CI): 1.363–1.5.391; P=0.004] and PFS (HR =3.365; 95% CI: 1.776–6.374; P<0.001). Multivariate analysis found that high serum LDH was associated with lower PFS (HR =2.122; 95% CI: 1.056–4.267; P=0.035). Moreover, high LDH was significantly associated with advanced Masaoka stage (P=0.001).
Conclusions
High serum LDH (>225 U/L) was an independent predictor of decreased PFS in thymic carcinoma patients. It was also significantly associated with reduced OS, but was not an independent predictor of death in those patients.
doi:10.21037/jtd.2016.08.56
PMCID: PMC5059350  PMID: 27746998
Thymic carcinoma; lactate dehydrogenase (LDH); prognosis
17.  Household Food Insecurity and Children's Behaviour Problems: New Evidence from a Trajectories-Based Study 
British Journal of Social Work  2015;46(4):993-1008.
This study examined the association between household food insecurity (insufficient access to adequate and nutritious food) and trajectories of externalising and internalising behaviour problems in children from kindergarten to fifth grade using longitudinal data from the Early Childhood Longitudinal Study—Kindergarten Cohort (ECLS-K), a nationally representative study in the USA. Household food insecurity was assessed using the eighteen-item standard food security scale, and children's behaviour problems were reported by teachers. Latent growth curve analysis was conducted on 7,348 children in the ECLS-K, separately for boys and girls. Following adjustment for an extensive array of confounding variables, results suggest that food insecurity generally was not associated with developmental change in children's behaviour problems. The impact of food insecurity on behaviour problems may be episodic or interact with certain developmental stages.
doi:10.1093/bjsw/bcv033
PMCID: PMC4986076  PMID: 27559210
Child development; externalising behaviour problem; food security; food insecurity; internalising behaviour problem
18.  Rock Outcrops Redistribute Organic Carbon and Nutrients to Nearby Soil Patches in Three Karst Ecosystems in SW China 
PLoS ONE  2016;11(8):e0160773.
Emergent rock outcrops are common in terrestrial ecosystems. However, little research has been conducted regarding their surface function in redistributing organic carbon and nutrient fluxes to soils nearby. Water that fell on and ran off 10 individual rock outcrops was collected in three 100 × 100 m plots within a rock desertification ecosystem, an anthropogenic forest ecosystem, and a secondary forest ecosystem between June 2013 and June 2014 in Shilin, SW China. The concentrations of total organic carbon (TOC), total nitrogen (N), total phosphorus (P), and potassium (K) in the water samples were determined during three seasons, and the total amounts received by and flowing out from the outcrops were calculated. In all three ecosystems, TOC and N, P, and K were found throughout the year in both the water received by and delivered to nearby soil patches. Their concentrations and amounts were generally greater in forested ecosystems than in the rock desertification ecosystem. When rock outcrops constituted a high percentage (≥ 30%) of the ground surface, the annual export of rock outcrop runoff contributed a large amount of organic carbon and N, P, and K nutrients to soil patches nearby by comparison to the amount soil patches received via atmospheric deposition. These contributions may increase the spatial heterogeneity of soil fertility within patches, as rock outcrops of different sizes, morphologies, and emergence ratios may surround each soil patch.
doi:10.1371/journal.pone.0160773
PMCID: PMC4980016  PMID: 27509199
19.  Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Ganglia of Human Gastrointestinal Tract 
Scientific Reports  2016;6:30926.
CF is caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) which is an anion selective transmembrane ion channel that mainly regulates chloride transport, expressed in the epithelia of various organs. Recently, we have demonstrated CFTR expression in the brain, the spinal cord and the sympathetic ganglia. This study aims to investigate the expression and distribution of CFTR in the ganglia of the human gastrointestinal tract. Fresh tissue and formalin-fixed paraffin-embedded normal gastrointestinal tract samples were collected from eleven surgical patients and five autopsy cases. Immunohistochemistry, in situ hybridization, laser-assisted microdissection and nested reverse transcriptase polymerase chain reaction were performed. Expression of CFTR protein and mRNA was detected in neurons of the ganglia of all segments of the human gastrointestinal tract examined, including the stomach, duodenum, jejunum, ileum, cecum, appendix, colon and rectum. The extensive expression of CFTR in the enteric ganglia suggests that CFTR may play a role in the physiology of the innervation of the gastro-intestinal tract. The presence of dysfunctional CFTRs in enteric ganglia could, to a certain extent, explain the gastrointestinal symptoms frequently experienced by CF patients.
doi:10.1038/srep30926
PMCID: PMC4974654  PMID: 27491544
20.  Advanced Mitigation Process (AMP) for Improving Laser Damage Threshold of Fused Silica Optics 
Scientific Reports  2016;6:31111.
The laser damage precursors in subsurface of fused silica (e.g. photosensitive impurities, scratches and redeposited silica compounds) were mitigated by mineral acid leaching and HF etching with multi-frequency ultrasonic agitation, respectively. The comparison of scratches morphology after static etching and high-frequency ultrasonic agitation etching was devoted in our case. And comparison of laser induce damage resistance of scratched and non-scratched fused silica surfaces after HF etching with high-frequency ultrasonic agitation were also investigated in this study. The global laser induce damage resistance was increased significantly after the laser damage precursors were mitigated in this case. The redeposition of reaction produce was avoided by involving multi-frequency ultrasonic and chemical leaching process. These methods made the increase of laser damage threshold more stable. In addition, there is no scratch related damage initiations found on the samples which were treated by Advanced Mitigation Process.
doi:10.1038/srep31111
PMCID: PMC4971457  PMID: 27484188
21.  Moracin C, A Phenolic Compound Isolated from Artocarpus heterophyllus, Suppresses Lipopolysaccharide-Activated Inflammatory Responses in Murine Raw264.7 Macrophages 
Artocarpus heterophyllus, a popular tropical fruit commonly known as the jackfruit tree, is normally planted in subtropical or tropical areas. Since a variety of phytochemicals isolated from A. heterophyllus have been found to possess potently anti-inflammatory, antiviral and antimalarial activities, researchers have devoted much interest to its potential pharmaceutical value. However, the exact mechanism underlying its anti-inflammatory activity is not well characterized. In this study, seven natural products isolated from A. heterophyllus, including 25-Hydroxycycloart-23-en-3-one (HY), Artocarpin (AR), Dadahol A (DA), Morachalcone A (MA), Artoheterophyllin B (AB), Cycloheterophyllin (CY) and Moracin C (MC) were collected. Lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 macrophages were used in this study. Among these compounds, MC significantly inhibited LPS-activated reactive oxygen species (ROS) and nitric oxide (NO) release without marked cytotoxicity. Furthermore, MC effectively reduced LPS stimulated up-regulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and serval pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)). Mechanistic studies revealed that the anti-inflammatory effect of MC was associated with the activation of the mitogen activated protein kinases (MAPKs) (including p38, ERK and JNK) and nuclear factor-κB (NF-κB) pathways, especially reducing the nuclear translocation of NF-κB p65 subunit as revealed by nuclear separation experiment and confocal microscopy.
doi:10.3390/ijms17081199
PMCID: PMC5000597  PMID: 27463712
inflammation; MAPKs; Moracin C; NF-κB; phenols
22.  Deciphering Transcriptome and Complex Alternative Splicing Transcripts in Mammary Gland Tissues from Cows Naturally Infected with Staphylococcus aureus Mastitis 
PLoS ONE  2016;11(7):e0159719.
Alternative splicing (AS) contributes to the complexity of the mammalian proteome and plays an important role in diseases, including infectious diseases. The differential AS patterns of these transcript sequences between the healthy (HS3A) and mastitic (HS8A) cows naturally infected by Staphylococcus aureus were compared to understand the molecular mechanisms underlying mastitis resistance and susceptibility. In this study, using the Illumina paired-end RNA sequencing method, 1352 differentially expressed genes (DEGs) with higher than twofold changes were found in the HS3A and HS8A mammary gland tissues. Gene ontology and KEGG pathway analyses revealed that the cytokine–cytokine receptor interaction pathway is the most significantly enriched pathway. Approximately 16k annotated unigenes were respectively identified in two libraries, based on the bovine Bos taurus UMD3.1 sequence assembly and search. A total of 52.62% and 51.24% annotated unigenes were alternatively spliced in term of exon skipping, intron retention, alternative 5′ splicing and alternative 3ʹ splicing. Additionally, 1,317 AS unigenes were HS3A-specific, whereas 1,093 AS unigenes were HS8A-specific. Some immune-related genes, such as ITGB6, MYD88, ADA, ACKR1, and TNFRSF1B, and their potential relationships with mastitis were highlighted. From Chromosome 2, 4, 6, 7, 10, 13, 14, 17, and 20, 3.66% (HS3A) and 5.4% (HS8A) novel transcripts, which harbor known quantitative trait locus associated with clinical mastitis, were identified. Many DEGs in the healthy and mastitic mammary glands are involved in immune, defense, and inflammation responses. These DEGs, which exhibit diverse and specific splicing patterns and events, can endow dairy cattle with the potential complex genetic resistance against mastitis.
doi:10.1371/journal.pone.0159719
PMCID: PMC4961362  PMID: 27459697
23.  Arabidopsis YL1/BPG2 Is Involved in Seedling Shoot Response to Salt Stress through ABI4 
Scientific Reports  2016;6:30163.
The chloroplast-localized proteins play roles in plant salt stress response, but their mechanisms remain largely unknown. In this study, we screened a yellow leaf mutant, yl1-1, whose shoots exhibited hypersensitivity to salt stress. We mapped YL1 to AT3G57180, which encodes a YqeH-type GTPase. YL1, as a chloroplast stroma-localized protein, could be markedly reduced by high salinity. Upon exposure to high salinity, seedling shoots of yl1-1 and yl1-2 accumulated significantly higher levels of Na+ than wild type. Expression analysis of factors involved in plant salt stress response showed that the expression of ABI4 was increased and HKT1 was evidently suppressed in mutant shoots compared with the wild type under normal growth conditions. Moreover, salinity effects on ABI4 and HKT1 were clearly weakened in the mutant shoots, suggesting that the loss of YL1 function impairs ABI4 and HKT1 expression. Notably, the shoots of yl1-2 abi4 double mutant exhibited stronger resistance to salt stress and accumulated less Na+ levels after salt treatment compared with the yl1-2 single mutant, suggesting the salt-sensitive phenotype of yl1-2 seedlings could be rescued via loss of ABI4 function. These results reveal that YL1 is involved in the salt stress response of seedling shoots through ABI4.
doi:10.1038/srep30163
PMCID: PMC4957093  PMID: 27444988
24.  Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure 
Medicine  2016;95(27):e4105.
Supplemental Digital Content is available in the text
Abstract
Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines. Interleukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure. Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it.
A total of 1713 adult patients with congestive heart failure and 1713 age- and sex-matched controls were genotyped for promoter single nucleotide polymorphisms (SNPs), rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure. Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.63–0.90, adjusted P = 0.002) after adjustment for multiple cardiovascular risk factors including age, sex, smoking status, diabetes, hypertension, and dyslipidemia. This association was evident in both ischemic and nonischemic heart failure (P = 0.005 and P = 0.05, respectively). Furthermore, prospective follow-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs4819554 in IL17RA was significantly associated with cardiovascular mortality (hazard ratio [HR] = 1.28; 95% CI = 1.02–1.59, adjusted P = 0.03) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class.
This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of congestive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure. These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure pathogenesis and progression.
doi:10.1097/MD.0000000000004105
PMCID: PMC5058840  PMID: 27399111
congestive heart failure; IL-17A; IL-17RA; single nucleotide polymorphism
25.  Impact of Experience Corps® Participation on School Climate 
We examined the impact of the Experience Corps® (EC) program on school climate within Baltimore City public elementary schools. In this program, teams of older adult volunteers were placed in high intensity (>15 hours per week), meaningful roles in public elementary schools, to improve the educational outcomes of children as well as the health and well-being of volunteers. During the first year of EC participation, school climate was perceived more favorably among staff and students in EC schools as compared to those in comparison schools. However, with a few notable exceptions, perceived school climate did not differ for staff or students in intervention and comparison schools during the second year of exposure to the EC program. These findings suggest that perceptions of school climate may be altered by introducing a new program into elementary schools; however, research examining how perceptions of school climate are impacted over a longer period is warranted.
doi:10.1007/s11121-015-0550-2
PMCID: PMC4456199  PMID: 25708453
academic achievement; classroom behavior; childhood education; school climate; older adult volunteers

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