Ambient air quality and the effects of air pollutants on otolaryngology in Beijing.

To investigate temporal patterns, pollution concentrations and the health effects of air pollutants in Beijing we carried out time-series analyses on daily concentrations of ambient air pollutants and daily numbers of outpatient visits for otolaryngology over 2 years (2011-2012) to identify possible health effects of air pollutants. The results showed that PM10 was the major air pollutant in Beijing and that air quality was slightly better in 2012 than in 2011. Seasonal differences were apparent for SO2 and NO2. Both the background and urban areas of Beijing experienced particulate matter pollution in 2011. In addition to local air pollution, Beijing was also affected by pollutants transported from other regions, especially during heavy air pollution episodes. PM10, NO2, and SO2 concentrations showed positive associations with numbers of outpatient visits for otolaryngology during winter. NO2 and SO2 also had adverse ear, nose, and throat health effects outside of winter. The ear, nose, and throat health risks caused by air pollutants were higher during the winter than during the summer. NO2 had stronger influence on increased the likelihood of outpatient visits than SO2. The findings provide additional information about air quality and health effects of air pollution in Beijing.

Variants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability.

Reading disability (RD) is a complex genetic disorder with unknown etiology. Genes on chromosome 6p22, including DCDC2, KIAA0319, and TTRAP, have been identified as RD associated genes. Imaging studies have shown both functional and structural differences between brains of individuals with and without RD. There are limited association studies performed between RD genes, specifically genes on 6p22, and regional brain activation during reading tasks. Using fourteen variants in DCDC2, KIAA0319, and TTRAP and exhaustive reading measures, we first tested for association with reading performance in 82 parent-offspring families (326 individuals). Next, we determined the association of these variants with activation of sixteen brain regions of interest during four functional magnetic resonance imaging-reading tasks. We nominally replicated associations between reading performance and variants of DCDC2 and KIAA0319. Furthermore, we observed a number of associations with brain activation patterns during imaging-reading tasks with all three genes. The strongest association occurred between activation of the left anterior inferior parietal lobe and complex tandem repeat BV677278 in DCDC2 (uncorrected p=0.00003, q=0.0442). Our results show that activation patterns across regions of interest in the brain are influenced by variants in the DYX2 locus. The combination of genetic and functional imaging data show a link between genes and brain functioning during reading tasks in subjects with RD. This study highlights the many advantages of imaging data as an endophenotype for discerning genetic risk factors for RD and other communication disorders and underscores the importance of integrating neurocognitive, imaging, and genetic data in future investigations.

[Time-series analysis on relationship between air pollution and mortality from circulatory system diseases among registered residents in Chaoyang district of Beijing].

OBJECTIVE: This study aims to investigate relationship between daily concentration of PM(10), SO(2), NO(2) and daily mortality due to circulatory system diseases in Chaoyang district, Beijing. METHODS: The time-series data of daily mortality from circulatory system diseases of registered residents in Chaoyang were obtained from Chaoyang District Center for Disease Control and Prevention. The daily concentration of sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and particulate matter (PM(10)) were collected from Beijing Municipal Environmental Monitoring Center. And the routine monitoring meteorological data were collected from Beijing Meteorological Bureau, including daily mean temperature and daily mean relative humidity. The time-series analysis was then conducted to determine the relationship of mortality from circulatory system diseases with daily concentrations of SO(2), NO(2) and PM(10) by using Poisson regression with generalized additive model (GAM). RESULTS: During January 2004 to September 2008, the cumulative death number from circulatory system diseases of registered residents in Chaoyang district of Beijing was 19 241, the daily average concentration of SO(2), NO(2), PM(10) was 48.7, 63.9, 146.1 µg/m(3), respectively. The single pollutant model showed an increase of daily concentration of PM(10), SO(2) and NO(2) by 10 µg/m(3) will augment the mortality from circulatory system diseases by 0.20% (95%CI: 0.01% - 0.39%), 0.36% (95%CI: -0.13% - 0.85%) and 0.30% (95%CI: -0.34% - 0.94%), respectively. In the multiple air pollutants models, combinatorial effects of PM(10) and SO(2) still positively correlated with increased mortality from circulatory system diseases (P < 0.05), whereas changes of the concentration of NO(2) had no significant effect on mortality from circulatory system diseases (P > 0.05). CONCLUSION: Our findings in this study elucidated that changes of the concentration of PM(10) and SO(2) had a positive correlation with daily mortality from circulatory system diseases among the local residents in Chaoyang District, whereas the daily concentration of NO(2) was irrelevant with that.

Analysis of the Relationship between Transformational Leadership and Educational Management in Higher Education Based on Deep Learning.

Leadership behavior has been emphasized as one of the most important influencing factors in the innovation process. Leaders can encourage subordinates to innovate by creating the right environment, promoting knowledge integration, and setting specific goals. However, different leadership styles make different decisions and behaviors in the innovation process, and the final innovation effect is also different. Today, in the context of China, most business leaders still adopt "paternalistic" or "authoritarian" leadership behaviors, but more and more entrepreneurs and scholars are aware of the importance of this leadership style in enhancing employee creativity. Authoritarian leaders are more likely to exercise more control and supervision over team members, limit the autonomy of team members, and reduce work initiative and creativity. Although the positive effect of transformational leadership on employee creativity has been recognized by some scholars, in the real work environment, this leadership style rarely appears, especially in the context of China. This study first constructs a theoretical model of how transformational leaders in colleges and universities affect educational management innovation through the atmosphere of school organizational innovation, based on the deep learning theory and other related research results, and then puts forward research hypotheses on this basis. Secondly, a measurement scale was designed according to the existing research results, and the scale was revised through the pretest to form the formal questionnaire of this study. This research uses cluster sampling and random sampling to conduct a questionnaire survey on 1022 college teachers and uses the SPSS20.0 and AMOS21.0 to conduct an empirical analysis on the survey data. Each measurement scale was tested by exploratory factor analysis and confirmatory factor analysis. The experimental results show that the transformational leadership style of college principals has a positive impact on teachers' teaching innovation. There is a positive correlation between the influence of charisma and teachers' teaching management, and there is a positive correlation between intellectual stimulation and teachers' teaching management.

A dyslexia-associated variant in DCDC2 changes gene expression.

Reading disability (RD) or dyslexia is a common neurogenetic disorder. Two genes, KIAA0319 and DCDC2, have been identified by association studies of the DYX2 locus on 6p21.3. We previously identified a 2445 bp deletion, and a compound STR within the deleted region (BV677278), in intron 2 of DCDC2. The deletion and several alleles of the STR are strongly associated with RD (P = 0.00002). In this study we investigated whether BV677278 is a regulatory region for DCDC2 by electrophoretic mobility shift and luciferase reporter assays. We show that oligonucleotide probes from the STR bind nuclear protein from human brain, and that alleles of the STR have a range of DCDC2-specific enhancer activities. Five alleles displayed strong enhancer activity and increased gene expression, while allele 1 showed no enhancer activity. These studies suggest that the association of BV677278 with RD reflects a role as a modifier of DCDC2 expression.

Actual causes of death in Chaoyang District of Beijing, China, 2007.

OBJECTIVES: To identify and quantify major external (non-genetic) factors that contribute to death in Chaoyang District of Beijing, China in 2007. METHODS: The death registration data reported to the Center of Disease Control and Prevention of Chaoyang District of Beijing, China, during the year 2007, were obtained. The analysis was conducted in 2009 using the health risk factors identified by the World Health Report 2002 and the population attributable fractions of mortality from Global burden of disease and risk factors. The estimates of actual causes of death attributable to each risk factor were calculated by multiplying the population attributable fractions of mortality by the corresponding number of deaths of the subgroup or total population. RESULTS: The five leading actual causes of death in Chaoyang District of Beijing, China in 2007 were high blood pressure (2159 deaths, 18%), smoking (990, 8%), low fruit and vegetable consumption (968, 8%), high cholesterol (891, 7%), and physical inactivity (629, 5%). The pattern and ordering of these leading causes vary with sex and age specific subgroups. CONCLUSIONS: More than half of the total number of deaths in Chaoyang District in 2007 could be attributed to a few major preventable risk factors. Although the study focused on only one district of Beijing in one single year, and is by no means comprehensive, its findings suggest that public health policies and programmes in China should address these public health concerns by focusing on these largely preventable risk factors for primary prevention.

Genetic approaches to complications of prematurity.

Over the last 15 years neonatal morbidity and mortality have changed little for very low birth weight (VLBW) babies despite significant technological and therapeutic advances. While clinical trials and animal models have until recently improved outcomes in this gestational age group, further productivity from these traditional sources are not likely. A recent study of monozygotic and dizygotic twins shows that the main determinants of neonatal morbidity and mortality in VLBW babies--bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage--have significant genetic components. Incremental improvements in the future, therefore, will likely depend on identification of these genetic components for targeting specific therapies. Cost-effective methods and resources, fueled by the Human Genome and HapMap Projects and recent successes in identifying genes for a small number of complex genetic diseases, are available now and through creative planning and timely implementation would likely yield useful results.

Detection of Turner syndrome using high-throughput quantitative genotyping.

CONTEXT: Turner syndrome (TS) is the most common genetic problem affecting women and occurs when an X chromosome is completely deleted, portions of an X chromosome are deleted, or chromosomal mosaicism occurs. Girls with TS may also have occult Y chromosome sequences. Whereas some girls with TS are identified in infancy or early childhood, many girls with TS are not detected until after 10 yr of age, resulting in delayed evaluation and treatment. OBJECTIVE: To prevent the delayed recognition and treatment of TS, a quantitative method of genotyping that can be performed as part of newborn screening is needed. DESIGN: To screen for sex chromosome abnormalities, we assembled a panel of informative single nucleotide polymorphism (SNP) markers that span the X chromosome from the dbSNP database. Pyrosequencing assays suitable for quantitative assessment of signal strength from single nucleotides were designed and used to genotype 46,XX; 46,XY; 45,X; and TS mosaics, examining zygosity and signal strength for individual alleles. Pyrosequencing assays were also designed for the detection of Y chromosome material. RESULTS: With just four informative SNP markers for the X chromosome, all TS girls with 45,X, partial X chromosome deletions, or mosaicism were identified with 100% sensitivity. In mosaic individuals, Y chromosomal material was detected with 100% sensitivity. CONCLUSION: These results suggest that inexpensive high-throughput screening is possible for TS and other sex chromosome disorders using quantitative genotyping approaches.

Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center's Experience.

BACKGROUND: There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES. OBJECTIVE: We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered. Moreover, we examined the potential cost-effectiveness of WES by examining the cost burden of diagnostic workups. METHODS: To determine the clinical utility of our hospital's clinical WES, we performed a retrospective review of the first 40 cases. We utilized dual bioinformatics analyses pipelines based on commercially available software and in-house tools. RESULTS: Of the first 40 clinical cases, we identified genetic defects in 12 (30%) patients, of which 47% of the mutations were previously unreported in the literature. Among the 12 patients with positive findings, seven have autosomal dominant disease and five have autosomal recessive disease. Ninety percent of the cohort opted to receive secondary findings and of those, secondary medical actionable results were returned in three cases. Among these positive cases, there are a number of novel mutations that are being reported here. The diagnostic workup included a significant number of genetic tests with microarray and single-gene sequencing being the most popular tests. Significantly, genetic diagnosis from WES led to altered patient medical management in positive cases. CONCLUSION: We demonstrate the clinical utility of WES by establishing the clinical diagnostic rate and its impact on medical management in a large pediatric center. The cost-effectiveness of WES was demonstrated by ending the diagnostic odyssey in positive cases. Also, in some cases it may be most cost-effective to directly perform WES. WES provides a unique glimpse into the complexity of genetic disorders.

A transcription map of the 6p22.3 reading disability locus identifying candidate genes.

BACKGROUND: Reading disability (RD) is a common syndrome with a large genetic component. Chromosome 6 has been identified in several linkage studies as playing a significant role. A more recent study identified a peak of transmission disequilibrium to marker JA04 (G72384) on chromosome 6p22.3, suggesting that a gene is located near this marker. RESULTS: In silico cloning was used to identify possible candidate genes located near the JA04 marker. The 2 million base pairs of sequence surrounding JA04 was downloaded and searched against the dbEST database to identify ESTs. In total, 623 ESTs from 80 different tissues were identified and assembled into 153 putative coding regions from 19 genes and 2 pseudogenes encoded near JA04. The identified genes were tested for their tissue specific expression by RT-PCR. CONCLUSIONS: In total, five possible candidate genes for RD and other diseases mapping to this region were identified.

[Genetic polymorphisms, function and clinical effect of HLA-G].

HLA-G is a non-classical major histocompatibility complex class I molecule that differs from the classical HLA I class molecules by (1) a limited polymorphism, (2) a tissue-restricted distribution and (3) a transcription of spliced messenger RNAs encoding for at least four membrane-bound and two soluble HLA-G isoforms. Extensive studies over the past few years have identified HLA-G as a molecule involved in immune tolerance. In this review, attempts were made to summarize the current state of knowledge of the polymorphisms, expression, function, the effects of HLA-G on immuno-associated disease, evolution of HLA-G and its utility in disease therapy.

[Relationship between HFE gene and hereditary hemochromatosis].

HFE gene is a major histocompatibility complex class I-like gene, which was identified as a candidate gene for hemochromatosis in 1996. The proposed role for HFE is its part in the regulation of the interaction of the transferrin receptor with transferrin. Hemochromatosis, the common autosomal recessive disease of iron overload, affects at least 1 in 300 Caucasians. The identification of the C282Y mutation in the HFE gene has led to population screening studies. Much of this work has also included the analysis of a second mutation, H63D, which appears to have a low penetrability. HFE protein was recently found to coprecipitate with the transferrin receptor and to affect the reaction between transferrin and the transferrin receptor. Functional data suggest that the mutation C282Y abolishes the association of the HFE protein with beta 2-microglobulin (beta 2M), making the complex unable to reach the cell surface. Clearly, if the mutation protein is unable to reach the cell surface, this regulatory feature is missing. The role of a second mutation in the HFE gene, H63D, is less clear. Current data suggest that this mutation protein can associate with beta 2-microglobulin and does reach the cell surface and that the defect lies in a failure to modify the affinity of the transferrin receptor for transferrin. This does not explain the low degree of penetrability associated with this mutation.

DCDC2 genetic variants and susceptibility to developmental dyslexia.

OBJECTIVE(S): Developmental dyslexia is a heritable condition, with genetic factors accounting for 44-75% of the variance in performance tests of reading component subphenotypes. Compelling genetic linkage and association evidence supports a quantitative trait locus in the 6p21.3 region that encodes a gene called DCDC2. In this study, we explored the contribution of two DCDC2 markers to dyslexia, related reading and memory phenotypes in nuclear families of Italian origin. METHODS: The 303 nuclear families recruited on the basis of having a proband with developmental dyslexia have been studied with 6p21.3 markers, BV677278 and rs793862. Marker-trait association was investigated by the quantitative transmission disequilibrium test (version 2.5.1) that allows for the analyses of quantitative traits. Seven phenotypes were used in association analyses, that is, word and nonword reading, word and nonword spelling, orthographic choice, memory, and the affected status based on inclusion criteria. RESULTS: Quantitative transmission disequilibrium test analyses yielded evidence for association between reading skills and the BV677278 deletion (empirical P-values=0.025-0.029) and between memory and BV677278 allele 10 (empirical P-value=0.0001). CONCLUSION: Our result adds further evidence in support of DCDC2 contributing to the deficits in developmental dyslexia. More specifically, our data support the view that DCDC2 influences both reading and memory impairments thus shedding further light into the etiologic basis and the phenotypic complexity of developmental dyslexia.

Polymorphism of DCDC2 Reveals Differences in Cortical Morphology of Healthy Individuals-A Preliminary Voxel Based Morphometry Study.

OBJECTIVE: The purpose of this investigation was to determine whether there is an association between the putative reading disability (RD) susceptibility gene Doublecortin Domain Containing 2 (DCDC2), and gray matter (GM) distribution in the brain, in a sample of healthy control individuals. METHOD: Fifty-six control subjects were genotyped for an RD-associated deletion in intron 2 of DCDC2. Voxel based morphometry (VBM) was used to examine structural magnetic resonance imaging (MRI) scans to assess GM differences between the two groups. RESULTS: Individuals heterozygous for the deletion exhibited significantly higher GM volumes in reading/language and symbol-decoding related brain regions including superior, medial and inferior temporal, fusiform, hippocampal/para-hippocampal, inferior occipito-parietal, inferior and middle frontal gyri, especially in the left hemisphere. GM values correlated with published data on regional DCDC2 expression in a lateralized manner. CONCLUSIONS: These data suggest a role for DCDC2 in GM distribution in language-related brain regions in healthy individuals.

Investigation of the DCDC2 intron 2 deletion/compound short tandem repeat polymorphism in a large German dyslexia sample.

Dyslexia is a complex disorder manifested by difficulties in learning to read and spell despite conventional instruction, adequate intelligence and sociocultural opportunity. It is among the most common neurodevelopmental disorders with a prevalence of 5-12%. The dyslexia susceptibility locus 2 on chromosome 6p21-p22 is one of the best-replicated linkage regions in dyslexia. On the basis of systematic linkage disequilibrium studies, the doublecortin domain containing protein 2 gene (DCDC2) was identified as a strong candidate gene in this region. Data from a US study have suggested a complex deletion/compound short tandem repeat (STR) polymorphism in intron 2 of DCDC2 as the causative mutation. In this study, we analyzed this polymorphism in 396 German dyslexia trios which included 376 trios previously providing strong support for the DCDC2 locus. We observed no significant deviation from random transmission, neither for the deletion nor for the alleles of the compound STR. We also did not find the deletion or any of the STR alleles to be in linkage disequilibrium with the 2-marker haplotype, which was associated with dyslexia in our sample. We thus conclude that the causative variant/s in DCDC2 conferring susceptibility to dyslexia in our sample remain/s to be identified.

TDT-association analysis of EKN1 and dyslexia in a Colorado twin cohort.

A candidate gene, EKN1, was recently described in a cohort from Finland for the dyslexia locus on chromosome 15q, DYX1. This report described a (2;15) (q11;21) translocation disrupting EKN1 that cosegregated with dyslexia in a two-generation family. It also characterized a sequence polymorphism in the 5' untranslated region and a missense mutation that showed significant association in 109 dyslexics compared to 195 controls (p=0.002 and p=0.006, respectively). To confirm these results we interrogated the same polymorphisms in a cohort of 150 nuclear families with dyslexia ascertained through the Colorado Learning Disabilities Research Center. Using QTDT analysis with nine individual quantitative tasks and two composite measures of reading performance, we could not replicate the reported association. We conclude that the polymorphisms identified in the Finland sample are unlikely to be functional DNA changes contributing to dyslexia, and that if variation in EKN1 is causal such changes are more likely to be in regulatory regions that were not sequenced in this study. Alternatively, the published findings of association with markers in EKN1 may reflect linkage disequilibrium with variation in another gene(s) in the region.

DCDC2 is associated with reading disability and modulates neuronal development in the brain.

DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we identified a large polymorphic deletion that encodes tandem repeats of putative brain-related transcription factor binding sites in intron 2 of DCDC2. Alleles of this compound repeat are in significant disequilibrium with multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of the brain where fluent reading occurs, and RNA interference studies show that down-regulation alters neuronal migration. The statistical and functional studies are complementary and are consistent with the latest clinical imaging data for RD. Thus, we propose that DCDC2 is a candidate gene for RD.