The etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are unclear. Chronic inflammation is considered the main pathology of IC/BPS. This study measured the serum c-reactive protein (CRP), nerve growth factor (NGF) and pro-inflammatory cytokine/chemokine interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 expression in patients with IC/BPS to elucidate the involvement of systemic inflammation in IC/BPS.
Serum samples were collected from 30 IC/BPS patients and 26 control subjects. The concentrations of serum nerve growth factor (NGF), IL-1β, IL-6, TNF-α, and IL-8 were quantified using a bead-based, human serum adipokine panel kit. Serum C-reactive protein (CRP) was also assessed. Differences of serum CRP, NGF, IL-1β, IL-6, TNF-α, and IL-8 levels between the IC/BPS patients and controls were compared, and correlations between CRP and pro-inflammatory cytokines and chemokine were also evaluated.
The results showed that CRP level (p = 0.031), NGF (p = 0.015) and pro-inflammatory cytokines/chemokine IL-1β, IL-6, TNF-α, and IL-8 levels were significantly higher in the patients with IC/BPS than among controls (all p<0.001). Significant associations were observed between IL-1β and IL-8 (p<0.001), IL-6 and CRP (p = 0.01), IL-6 and IL-8 (p = 0.02), and IL-6 and TNF-α (p = 0.03).
Increased pro-inflammatory cytokines/chemokine (IL-1β, IL-6, TNF-α, and IL-8) expression in the sera of IC/BPS patients implies not only mast cell activation, but also that other inflammatory mediators play important roles in the pathogenesis of IC/BPS. Thus, for some patients, IC/BPS is considered a chronic inflammatory disease.
Recent studies have shown that chronic inflammation is involved in overactive bladder (OAB) syndrome. OAB could be a subtype of neurogenic inflammation. This pilot study investigated serum adipokine levels in patients with OAB refractory to antimuscarinic therapy.
Thirty consecutive patients with OAB-dry (n = 16) or OAB-wet (n = 14) refractory to previous antimuscarinic treatment were prospectively enrolled in this study, a group of 26 normal subjects without lower urinary tract symptoms served as controls. Concentrations of serum C-reactive protein (CRP), nerve growth factor (NGF), and adipokines including interleukins ([IL], IL-1β, IL-6, IL-8), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, insulin, and leptin were quantified using a bead-based human serum adipokine panel B kit. Data were analyzed using the LX 200 platform. Patients were further classified as having dry or wet OAB and having medical diseases or not. The serum CRP, NGF, and adipokine levels were compared between OAB patients and the controls, and between OAB subgroups.
The serum concentrations of CRP, NGF, IL-1β, IL-6, IL-8, and TNF-α in OAB-dry and OAB-wet patients were significantly higher than among the controls. There was no significant difference in adipokine levels between OAB-dry and OAB-wet, or between OAB patients with and without medical diseases. Serum CRP and NGF levels were significantly higher only in OAB-wet or OAB patients with medical diseases than among controls. The MCP-1 levels, on the other hand, were significantly higher in OAB-dry or OAB patients with disease, than the controls.
Both OAB-dry and OAB-wet patients showed increased serum CRP, NGF, and adipokine levels compared with the controls, suggesting chronic inflammation of the bladder involving both peripheral and central mechanisms in all OAB patients refractory to antimuscarinic therapy. The increased serum adipokine levels were not relevant to medical diseases.
Understanding and predicting ecosystem functioning such as biomass accumulation requires an accurate assessment of large-scale patterns of biomass distribution and partitioning in relation to climatic and soil environments.
We sampled above- and belowground biomass from 26 sites spanning 1500 km in Inner Mongolian grasslands, compared the difference in aboveground, belowground biomass and below-aboveground biomass ratio (AGB, BGB, and B/A, respectively) among meadow steppe, typical steppe, and desert steppe types. The relationships between AGB, BGB, B/A and climatic and soil environments were then examined.
We found that AGB and BGB differed significantly among three types of grasslands while B/A did not differ. Structural equation model analyses indicated that mean annual precipitation was the strongest positive driver for AGB and BGB. AGB was also positively associated with soil organic carbon, whereas B/A was positively associated with total soil nitrogen.
These results indicated that precipitation positively influence plant production in Inner Mongolian grasslands. Contrary to the prediction from the optimal partitioning hypothesis, biomass allocation to belowground increased with soil total nitrogen, suggesting that more productive sites may increase belowground allocation as an adaptive strategy to potentially high fire frequencies.
Offspring of pregnancy complicated with preeclampsia are at high risk for hypertension, stroke and possibly obesity. The mechanisms behind the association of intrauterine exposure to preeclampsia and high risk of health problems in the later life remain largely unknown. The aims of the current investigation were to determine the changes in DNA methylation at IGF2 and GNAS DMR in offspring of preeclamptic pregnancy and to explore the possible mechanisms underlying the association between maternal preeclampsia and high risk for health problems in the later life of their offspring.
Umbilical cord blood was taken from infants born to women of preeclampsia (n=56), gestational hypertension (n=23) and normal pregnancy (n=81). DNA methylation levels of IGF2 and GNAS DMR were determined by Massarray quantitative methylation analysis. Methylation levels at IGF2 DMR were significantly lower in preeclampsia than normal pregnancy. The average methylation level at IGF2 DMR was significantly correlated with preeclampsia even after birth weight, maternal age, gestational age at delivery and fetal gender were adjusted. The difference in methylation level was not significantly different between mild and severe preeclampsia. The methylation level at GNAS DMR was not significantly correlated with birth weight, maternal age, gestational age at delivery, fetal gender, preeclampsia or gestational hypertension.
We concluded preeclampsia induced a decrease in methylation level at IGF 2 DMR, and this might be among the mechanisms behind the association between intrauterine exposure to preeclampsia and high risk for metabolic diseases in the later life of the infants.
Preeclampsia; Offspring; DNA methylation; IGF2; GNAS; Metabolic diseases
To examine the secondhand smoke (SHS) exposure level in Chinese office buildings and to evaluate the effectiveness of a smoke-free policy in reducing SHS exposure.
Survey of smoking policies and measurement of SHS level in 14 office buildings from 10 provinces in China.
Smoking in the building significantly elevated the SHS concentrations both in offices with at least one smoker and in offices with no smokers. In one building that recently adopted a smoke-free policy, the nicotine concentrations decreased significantly after the policy was enacted. Enactment of a smoking policy was effective in reducing SHS exposure in the buildings.
Nonsmoking office workers in China were exposed to significant levels of SHS at work; both the central and local governments should realize the need to legislate against workplace smoking.
Eukaryotic mitogen-activated protein kinase (MAPK/MPK) signaling cascades transduce and amplify environmental signals via three types of reversibly phosphorylated kinases to activate defense gene expression. Canola (oilseed rape, Brassica napus) is a major crop in temperate regions. Identification and characterization of MAPK and MAPK kinases (MAPKK/MKK) of canola will help to elucidate their role in responses to abiotic and biotic stresses.
We describe the identification and analysis of seven MKK (BnaMKK) and 12 MPK (BnaMPK) members from canola. Sequence alignments and phylogenetic analyses of the predicted amino acid sequences of BnaMKKs and BnaMPKs classified them into four different groups. We also examined the subcellular localization of four and two members of BnaMKK and BnaMPK gene families, respectively, using green fluorescent protein (GFP) and, found GFP signals in both nuclei and cytoplasm. Furthermore, we identified several interesting interaction pairs through yeast two-hybrid (Y2H) analysis of interactions between BnaMKKs and BnaMPKs, as well as BnaMPK and BnaWRKYs. We defined contiguous signaling modules including BnaMKK9-BnaMPK1/2-BnaWRKY53, BnaMKK2/4/5-BnaMPK3/6-BnaWRKY20/26 and BnaMKK9-BnaMPK5/9/19/20. Of these, several interactions had not been previously described in any species. Selected interactions were validated in vivo by a bimolecular fluorescence complementation (BiFC) assay. Transcriptional responses of a subset of canola MKK and MPK genes to stimuli including fungal pathogens, hormones and abiotic stress treatments were analyzed through real-time RT-PCR and we identified a few of BnaMKKs and BnaMPKs responding to salicylic acid (SA), oxalic acid (OA), Sclerotinia sclerotiorum or other stress conditions. Comparisons of expression patterns of putative orthologs in canola and Arabidopsis showed that transcript expression patterns were generally conserved, with some differences suggestive of sub-functionalization.
We identified seven MKK and 12 MPK genes from canola and examined their phylogenetic relationships, transcript expression patterns, subcellular localization, and protein-protein interactions. Not all expression patterns and interactions were conserved between canola and Arabidopsis, highlighting the limitations of drawing inferences about crops from model species. The data presented here provide the first systematic description of MKK-MPK-WRKY signaling modules in canola and will further improve our understanding of defense responses in general and provide a basis for future crop improvement.
Abiotic stress; Biotic stress; Brassica napus; MKK; MPK; Sclerotinia sclerotiorum; WRKY
Better understanding of acute stress responses is important for revision of DSM-5. However, the latent structure and relationship between different aspects of acute stress responses haven’t been clarified comprehensively. Bifactor item response model may help resolve this problem.
The purpose of this study is to develop a statistical model of acute stress responses, based on data from earthquake rescuers using Acute Stress Response Scale (ASRS). Through this model, we could better understand acute stress responses comprehensively, and provide preliminary information for computerized adaptive testing of stress responses.
Acute stress responses of earthquake rescuers were evaluated using ASRS, and state/trait anxiety were assessed using State-trait Anxiety Inventory (STAI). A hierarchical item response model (bifactor model) was used to analyze the data. Additionally, we tested this hierarchical model with model fit comparisons with one-dimensional and five-dimensional models. The correlations among acute stress responses and state/trait anxiety were compared, based on both the five-dimensional and bifactor models.
Model fit comparisons showed bifactor model fit the data best. Item loadings on general and specific factors varied greatly between different aspects of stress responses. Many symptoms (40%) of physiological responses had positive loadings on general factor, and negative loadings on specific factor of physiological responses, while other stress responses had positive loadings on both general and specific factors. After extracting general factor of stress responses using bifactor analysis, significant positive correlations between physiological responses and state/trait anxiety (r = 0.185/0.112, p<0.01) changed into negative ones (r = −0.177/−0.38, p<0.01).
Our results demonstrated bifactor structure of acute stress responses, and positive and negative correlations between physiological responses and stress responses suggested physiological responses could have negative feedback on severity of stress responses. This finding has not been convincingly demonstrated in previous research.
Background. Specific dietary components have been associated with gastroesophageal reflux disease (GERD) in Europe and the United States. However, the relationship between dietary components and GERD in Chinese still remains unclear. Methods. A total of 268 patients who were newly diagnosed as reflux esophagitis (RE) in Outpatient Endoscopy Center of Tongji Hospital were recruited. In addition, 269 sex- and age-matched subjects were also recruited as controls. The body measurements were determined, and the dietary intake during the previous year was evaluated using food frequency questionnaire (FFQ). Stepwise multiple logistic regression analysis was performed to examine the association between nutrients and RE. Results. After adjustment for WC, WHR, total energy intake, and demographics, there were a positive dose-response relationship between RE and calcium, meat, oils, and salt and a negative dose-response relationship between RE and protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs. Conclusion. High intake of meat, oils, salt, and calcium is associated with an increased risk for RE while high intake of protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs correlates with a reduced risk for RE.
Apoptosis of photoreceptors plays a critical role in the vision loss caused by retinal detachment (RD). Pharmacologic inhibition of photoreceptor cell death may prevent RD. This study investigated the role of GADD153 that participates in endoplasmic reticulum (ER) stress-mediated apoptosis of photoreceptor cells after RD.
Retinal detachment was created in Wistar rats by subretinal injection of hyaluronic acid. The rats were then randomly divided into four groups: normal control group, RD group, GADD153 RNAi group and vehicle group. RNA interference of GADD153 was performed using short hairpin RNA (shRNA). Expressions of GADD153 mRNA and protein were examined by RT-PCR and Western blotting analysis, respectively. GADD153 protein distribution in the retinal cells was observed using immunofluorescence confocal laser scanning microscopy. Apoptosis of retinal cells was determined by TdT-mediated fluorescein-16-dUTP nick-end labeling (TUNEL) assay.
Lentivirus GADD153 shRNA with the most effective silencing effect was chosen for in vivo animal study and was successfully delivered into the retinal tissues. GADD153 mRNA and protein expressions in GADD153 RNAi group were significantly lower than those in the RD group. Silencing of GADD153 by RNAi protected photoreceptors from ER stress-induced apoptosis.
ER stress-mediated pathway is involved in photoreceptor cell apoptosis after RD. GADD153 is a key regulatory molecule regulating ER-stress pathways and plays a crucial role in the apoptosis of photoreceptor cells after RD.
p53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) on the risk of breast cancer; therefore, a meta-analysis was performed to estimate the association between the p53 codon 72 polymorphism and breast cancer. Screening of the PubMed database was conducted to identify relevant studies. Studies containing available genotype frequencies of the p53 codon 72 polymorphism were selected and a pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Sixty-one published studies, including 28,539 breast cancer patients and 32,788 controls were identified. The results suggest that variant genotypes are not associated with breast cancer risk (Pro/Pro + Arg/Pro vs. Arg/Arg: OR=1.016, 95% CI=0.931–1.11, P=0.722). The symmetric funnel plot, Egger’s test (P=0.506) and Begg’s test (P=0.921) were all suggestive of the lack of publication bias. This meta-analysis suggests that the p53 codon 72 Pro/Pro + Arg/Pro genotypes are not associated with an increased risk of breast cancer. To validate the association between the p53 codon 72 polymorphism and breast cancer, further studies with larger numbers of participants worldwide are required.
p53; meta-analysis; breast cancer
The aim of this study was to investigate the predictive values of the total International Prostate Symptom Score (IPSS-T) and voiding to storage subscore ratio (IPSS-V/S) in association with total prostate volume (TPV) and maximum urinary flow rate (Qmax) in the diagnosis of bladder outlet-related lower urinary tract dysfunction (LUTD) in men with lower urinary tract symptoms (LUTS).
A total of 298 men with LUTS were enrolled. Video-urodynamic studies were used to determine the causes of LUTS. Differences in IPSS-T, IPSS-V/S ratio, TPV and Qmax between patients with bladder outlet-related LUTD and bladder-related LUTD were analyzed. The positive and negative predictive values (PPV and NPV) for bladder outlet-related LUTD were calculated using these parameters.
Of the 298 men, bladder outlet-related LUTD was diagnosed in 167 (56%). We found that IPSS-V/S ratio was significantly higher among those patients with bladder outlet-related LUTD than patients with bladder-related LUTD (2.28±2.25 vs. 0.90±0.88, p<0.001). TPV was similar between the two groups; however, in contrast to patients with bladder-related LUTD, patients with bladder outlet-related LUTD had higher detrusor voiding pressure, lower Qmax values, and greater postvoid residual volumes. The combination of TPV30 ml and Qmax10 ml/sec had a PPV of 68.8% and a NPV of 53.5% for bladder outlet-related LUTD. When IPSS-T12 or IPSS-T15 was considered as an additional criterion, PPV increased to 75.0% and 78.5%, respectively, and the NPV decreased to 50.9% and 50.2%, respectively. When IPSS-V/S>1 or >2 was factored into the equation instead of IPSS-T, PPV were 91.4% and 97.3%, respectively, and NPV were 54.8% and 49.8%, respectively.
Combination of IPSS-T with TPV and Qmax increases the PPV of bladder outlet-related LUTD. Furthermore, including IPSS-V/S>1 or >2 into the equation results in a higher PPV than IPSS-T. IPSS-V/S>1 is a stronger predictor of bladder outlet-related LUTD than IPSS-T.
Two diametric paradigms have been proposed to model the molecular co-evolution of microbial mutualists and their eukaryotic hosts. In one, mutualist and host exhibit an antagonistic arms race and each partner evolves rapidly to maximize their own fitness from the interaction at potential expense of the other. In the opposing model, conflicts between mutualist and host are largely resolved and the interaction is characterized by evolutionary stasis. We tested these opposing frameworks in two lineages of mutualistic rhizobia, Sinorhizobium fredii and Bradyrhizobium japonicum. To examine genes demonstrably important for host-interactions we coupled the mining of genome sequences to a comprehensive functional screen for type III effector genes, which are necessary for many Gram-negative pathogens to infect their hosts. We demonstrate that the rhizobial type III effector genes exhibit a surprisingly high degree of conservation in content and sequence that is in contrast to those of a well characterized plant pathogenic species. This type III effector gene conservation is particularly striking in the context of the relatively high genome-wide diversity of rhizobia. The evolution of rhizobial type III effectors is inconsistent with the molecular arms race paradigm. Instead, our results reveal that these loci are relatively static in rhizobial lineages and suggest that fitness conflicts between rhizobia mutualists and their host plants have been largely resolved.
Rhizobia are an important group of bacteria that can enter into mutually beneficial symbiotic interactions with legume plants to fix atmospheric nitrogen. However, in order to do so, a complex dialog involving the exchange of chemical and molecular signals must occur between partners. Some species of beneficial rhizobia employ a type III secretion system, a well-characterized virulence mechanism used by pathogens to inject bacterial-encoded type III effector proteins directly into host cells to coerce the host into accommodating the microbe. In this study, we generated draft genome sequences and employed computational as well as experimental methods to identify type III effectors from eight strains representing Sinorhizobium fredii and Bradyrhizobium japonicum. We demonstrate that the type III effector genes of these rhizobial species are highly conserved in content with little diversity between strains. This work is an important step towards understanding the roles for type III secretion systems and their effectors in mutualistic interactions.
Substance dependence is a complex environmental and genetic disorder with significant social and medical concerns. Understanding the etiology of substance dependence is imperative to the development of effective treatment and prevention strategies. To this end, substantial effort has been made to identify genes underlying substance dependence, and in recent years, genome-wide association studies (GWASs) have led to discoveries of numerous genetic variants for complex diseases including substance dependence. Most of the GWAS discoveries were only based on single nucleotide polymorphisms (SNPs) and a single dichotomized outcome. By employing both SNP- and gene-based methods of analysis, we identified a strong (odds ratio = 13.87) and significant (P value = 1.33E − 11) association of an SNP in the NCK2 gene on chromosome 2 with opiates addiction in African-origin men. Codependence analysis also identified a genome-wide significant association between NCK2 and comorbidity of substance dependence (P value = 3.65E − 08) in African-origin men. Furthermore, we observed that the association between the NCK2 gene (P value = 3.12E − 10) and opiates addiction reached the gene-based genome-wide significant level. In summary, our findings provided the first evidence for the involvement of NCK2 in the susceptibility to opiates addiction and further revealed the racial and gender specificities of its impact.
Zinc finger, DHHC-type containing 2 (ZDHHC2), originally named as reduced expression associated with metastasis protein (REAM), has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma.
Quantitative Real-Time PCR (qRT-PCR) and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472) of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001) and histological grade (p<0.001). Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001).
Our data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.
Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.
Identifying the risk factors for comorbidity is important in psychiatric research. Empirically, studies have shown that testing multiple, correlated traits simultaneously is more powerful than testing a single trait at a time in association analysis. Furthermore, for complex diseases, especially mental illnesses and behavioral disorders, the traits are often recorded in different scales such as dichotomous, ordinal and quantitative. In the absence of covariates, nonparametric association tests have been developed for multiple complex traits to study comorbidity. However, genetic studies generally contain measurements of some covariates that may affect the relationship between the risk factors of major interest (such as genes) and the outcomes. While it is relatively easy to adjust these covariates in a parametric model for quantitative traits, it is challenging for multiple complex traits with possibly different scales. In this article, we propose a nonparametric test for multiple complex traits that can adjust for covariate effects. The test aims to achieve an optimal scheme of adjustment by using a maximum statistic calculated from multiple adjusted test statistics. We derive the asymptotic null distribution of the maximum test statistic, and also propose a resampling approach, both of which can be used to assess the significance of our test. Simulations are conducted to compare the type I error and power of the nonparametric adjusted test to the unadjusted test and other existing adjusted tests. The empirical results suggest that our proposed test increases the power through adjustment for covariates when there exist environmental effects, and is more robust to model misspecifications than some existing parametric adjusted tests. We further demonstrate the advantage of our test by analyzing a data set on genetics of alcoholism.
Comorbidity; Environmental factor; Family-based association test; Maximum test statistic; Multiple traits; Ordinal traits
Background and aims: Synchronous liver metastasis (SLM) remains a significant problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte growth factor (HGF) and Met plays an important role in cancer invasion and metastasis and is being developed to be targeted drugs. We aimed to investigate the role of HGF/Met in SLM based on a case-matched study and comparison between primary tumors and matched metastases.
Methods: A group of 30 patients with SLM and other two groups of patients without SLM in a hospital database were collected. They were matched into according to clinicopathological factors. 81 patients were included in the study. Their tissues of primary colorectal cancers, lymph nodes and liver metastases were collected to detect HGF and Met expression by immunohistochemistry and RT-PCR.
Results: Expression of HGF and Met at the protein level and the RNA level in primary CRCs with SLM were significantly higher than that in primary colorectal carcinomas without liver metastases (all P value<0.05). Their expression was only related to SLM when concurrent with regional lymph node metastasis (all P value<0.05) but had little influence on SLM without involvement of lymph node metastasis (all P value>0.05). Comparison their expression between primary tumors and matched metastases, major concordance and minor difference existed.
Conclusions: HGF and Met may exert functions in the development of SLM when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, further indicating their roles and potential values for a subtype of colorectal cancer metastasis. Major concordance and minor difference exist between primary tumors and matched metastases, which further provides evidence for evaluating the response to their inhibitors based on primary tumors or metastases.
colorectal carcinoma; synchronous liver metastasis; hepatocyte growth factor; Met.
The increase in urban migrants is one of major challenges for tuberculosis control in China. The different characteristics of tuberculosis cases between urban migrants and local residents in China have not been investigated before.
We performed a retrospective study of all pulmonary tuberculosis patients reported in Songjiang district, Shanghai, to determine the demographic, clinical and microbiological characteristics of tuberculosis cases between urban migrants and local residents. We calculated the odds ratios (OR) and performed multivariate logistic regression to identify the characteristics that were independently associated with tuberculosis among urban migrants. A total of 1,348 pulmonary tuberculosis cases were reported during 2006–2008, among whom 440 (32.6%) were local residents and 908 (67.4%) were urban migrants. Urban migrant (38.9/100,000 population) had higher tuberculosis rates than local residents (27.8/100,000 population), and the rates among persons younger than age 35 years were 3 times higher among urban migrants than among local residents. Younger age (adjusted OR per additional year at risk = 0.92, 95% CI: 0.91–0.94, p<0.001), poor treatment outcome (adjusted OR = 4.12, 95% CI: 2.65–5.72, p<0.001), and lower frequency of any comorbidity at diagnosis (adjusted OR = 0.20, 95% CI: 0.13–0.26, p = 0.013) were significantly associated with tuberculosis patients among urban migrants. There were poor treatment outcomes among urban migrants, mainly from transfers to another jurisdiction (19.3% of all tuberculosis patients among urban migrants).
A considerable proportion of tuberculosis cases in Songjiang district, China, during 2006–2008 occurred among urban migrants. Our findings highlight the need to develop and implement specific tuberculosis control strategies for urban migrants, such as more exhaustive case finding, improved case management and follow-up, and use of directly observed therapy (DOT).
Giving cigarettes as gifts is a common practice in China, but there have been few systematic studies of this practice. The present study was designed to estimate the incidence of receiving cigarettes as gifts, correlates of this practice, and its impact on brand selection in a representative sample of urban adult smokers in China.
Data were analyzed from Wave 2 of the International Tobacco Control (ITC) China Survey, where 4843 adult urban smokers were interviewed in six major Chinese cities between October 2007 and January 2008. The incidence of most recent cigarette acquisition due to gifting and the prevalence of preferred brand selection due to having received it as a gift were estimated. Bivariate and adjusted logistic regression models were estimated to identify factors associated with these two outcomes.
The incidence of receiving cigarettes as a gift at most recent cigarette acquisition was 3.5%. Smokers who received these gifted cigarettes were more likely to be female, older, have higher educational attainment, live in Beijing, and smoke fewer cigarettes per day. The prevalence of choosing one’s preferred brand due to having received it as a gift was 7.0%, and this was more likely among smokers who lived in Beijing and Guangzhou, had lower educational attainment, smoked less frequently, and had smoked their preferred brand for less than one year.
The 3.5% incidence of one’s most recent cigarette acquisition due to gifting is consistent with prevalence estimates based on longer reference periods and translates into the average smoker receiving a gift of cigarettes approximately five times a year. Gifting also appears to have a significant influence on brand preference. Tobacco control interventions in China may need to denormalize the practice of giving cigarettes as gifts in order to decrease the social acceptability of smoking.
Tobacco; Cigarette gifting; Preferred cigarette brand
Due to the emergence of drug-resistance, first-line therapy with fluconazole (FLC) increasingly resulted in clinical failure for the treatment of candidemia. Our previous studies found that in vitro RTA2 was involved in the calcineurin-mediated resistance to FLC in C. albicans. In this study, we found that calcium-activated-calcineurin significantly reduced the in vitro sensitivity of C. albicans to FLC by blocking the impairment of FLC to the plasma membrane via Rta2p. Furthermore, we found that RTA2 itself was not involved in C. albicans virulence, but the disruption of RTA2 dramatically increased the therapeutic efficacy of FLC in a murine model of systemic candidiasis. Conversely, both re-introduction of one RTA2 allele and ectopic expression of RTA2 significantly reduced FLC efficacy in a mammalian host. Finally, we found that calcium-activated-calcineurin, through its target Rta2p, dramatically reduced the efficacy of FLC against candidemia. Given the critical roles of Rta2p in controlling the efficacy of FLC, Rta2p can be a potential drug target for antifungal therapies.
Approximately 30 sex-chromosome discordant chimera cases have been reported to date, of which only four cases carried trisomy 21. Here, we present an additional case, an aborted fetus with a karyotype of 47,XX, +21/46,XY.
Autopsy demonstrated that this fetus was normally developed and had male genitalia. Major characteristics of Down syndrome were not observed except an enlarged gap between the first and second toes. Karyotyping of tissues cultured from the fetus revealed the same chimeric chromosomal composition detected in the amniotic fluid but with a different ratio of [47,XX,+21] to [46,XY]. Further short tandem repeat analysis indicated a double paternal contribution and single maternal contribution to the fetus, with the additional chromosome 21 in the [47,XX,+21] cell lineage originating from the paternal side.
We thus propose that this chimeric fetus was formed via the dispermic fertilization of a parthenogenetic ovum with one (Y) sperm and one (X,+21) sperm.
Chimerism; Trisomy 21; Sex chromosome; Fetus; Genitalia; Karyotype
Dysregulation of mechanisms that govern the control of epithelial cell polarity, morphology and plasticity are emerging as key processes in tumor progression. In this study we report amplification and overexpression of PAR6B, an essential component in epithelial cell tight junction (TJ) formation and maintenance of apico-basal polarity, in breast cancer cell lines. Analysis of chromosome 20q13.13 in 11 breast cancer cell lines by fluorescence in situ hybridization (FISH) identified a novel small amplicon centered at PARD6B in 5 cell lines, with copy number ranging from 7 to 27. The presence of the PARD6B amplicon correlated with PARD6B transcript and PAR6B protein abundance. Expression of related isoforms PARD6A and PARD6G were detectable at significantly lower levels. PARD6B overexpression correlated with TJ network formation in cultured cell monolayers. SiRNA-mediated inhibition of PAR6B in MCF7 resulted in loss of TJ assembly and membrane localization of atypical PKCζ (aPKC), but did not affect adherens junction formation. SiRNA-mediated inhibition of CDC42 in MCF7 also resulted in loss of TJ networks, confirming the requirement of a complete PAR6-aPKC-CDC42-PAR3 complex to activate and stabilize TJs. Immunohistochemical analysis of PAR6B expression on breast tumor microarrays indicated exquisite epithelial cell-specificity. Few quantitative differences in staining were observed between normal epithelium and adjacent tumor margins. However staining appeared reduced and cytoplasmic in more poorly differentiated tumors. We propose that quantitative imbalances in the components of pathways governing normal epithelial cell polarity arising from gain or loss of function may radically alter epithelial cell architecture and contribute to tumor progression.
Breast Cancer; DNA amplification; tight junction; siRNA; polarity; adhesion; PARD6B; PAR6B; CDC42; PKCζ
To examine predictors of quitting behaviours among adult smokers in China, in light of existing knowledge from previous research in four western countries and two southeast Asian countries.
Face-to-face interviews were carried out with smokers in 2006 using the International Tobacco Control (ITC) China Survey, with follow-up about 16 months later. A stratified multi-stage cluster sampling design was employed.
Beijing and other five cities in China.
A total of 4732 smokers were first surveyed in 2006. Of these, 3863 were recontacted in 2007, with a retention rate of 81.6%.
Baseline measures of sociodemographics, dependence and interest in quitting were used prospectively to predict both making quit attempts and staying quit among those who attempted.
Overall, 25.3% Chinese smokers reported having made at least one quit attempt between Waves 1 and 2; of these, 21.7% were still stopped at Wave 2. Independent predictors of making quit attempts included having higher quitting self-efficacy, previous quit attempts, more immediate intentions to quit, longer time to first cigarette upon waking, negative opinion of smoking and having smoking restrictions at home. Independent predictors of staying quit were being older, having longer previous abstinence from smoking, and having more immediate quitting intentions.
Predictors of Chinese smokers’ quitting behaviours are somewhat different to those found in previous research from other countries. Nicotine dependence and self-efficacy seem to be more important for attempts than for staying quit in China, and quitting intentions are related to both attempts and staying quit.
Group 14 of Genetic Analysis Workshop 17 examined several issues related to analysis of complex traits using DNA sequence data. These issues included novel methods for analyzing rare genetic variants in an aggregated manner (often termed collapsing rare variants), evaluation of various study designs to increase power to detect effects of rare variants, and the use of machine learning approaches to model highly complex heterogeneous traits. Various published and novel methods for analyzing traits with extreme locus and allelic heterogeneity were applied to the simulated quantitative and disease phenotypes. Overall, we conclude that power is (as expected) dependent on locus-specific heritability or contribution to disease risk, large samples will be required to detect rare causal variants with small effect sizes, extreme phenotype sampling designs may increase power for smaller laboratory costs, methods that allow joint analysis of multiple variants per gene or pathway are more powerful in general than analyses of individual rare variants, population-specific analyses can be optimal when different subpopulations harbor private causal mutations, and machine learning methods may be useful for selecting subsets of predictors for follow-up in the presence of extreme locus heterogeneity and large numbers of potential predictors.
rare variants; LASSO; machine learning; random forests; logic regression; binary trees; Poisson regression; ISIS; classification trees; meta-analysis; extreme sampling