Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% ...of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome.
We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls.
Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.
HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
Background
Diet and exercise during pregnancy have been used to prevent gestational diabetes mellitus (GDM) with some success.
Objective
To examine the effectiveness of lifestyle intervention on GDM ...prevention and to identify key effectiveness moderators to improve the prevention strategy.
Search strategy
Pubmed, Scopus, Cochrane, and cross‐references were searched.
Selection criteria
Randomised controlled trials (RCTs) evaluating lifestyle interventions during pregnancy for GDM prevention.
Data collection and analysis
Two independent reviewers extracted data. A random‐effects model was used to analyse the relative risk (RR) and 95% confidence interval (95% CI). Meta‐regressions and subgroup analyses were used to investigate important moderators of effectiveness.
Main results
Forty‐seven RCTs involving 15 745 participants showed that diet and exercise during pregnancy were preventive of GDM (RR 0.77, 95% CI 0.69–0.87). Four key aspects were identified to improve the preventive effect: targeting the high‐risk population; an early initiation of the intervention; the correct intensity and frequency of exercise; and gestational weight gain management. Although 24 RCTs targeted women who were overweight or obese, body mass index (BMI) failed to predict the effectiveness of an intervention. Instead, interventions are most effective in high‐incidence populations rather than simply in women who are overweight or obese. Furthermore, exercise of moderate intensity for 50–60 minutes twice a week could lead to an approximately 24% reduction in GDM.
Conclusion
The best strategy to prevent GDM is to target the high‐risk population predicted by risk evaluation models and to control the gestational weight gain of women through intensified diet and exercise modifications early in their pregnancy.
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Four key effectiveness moderators of lifestyle interventions for GDM prevention.
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Four key effectiveness moderators of lifestyle interventions for GDM prevention.
Background and purpose: The incidence of ischaemic stroke has increased or remained high in China; however, little population‐based evidence is available on the incidence and survival of lacunar ...infarction (LAC). We examined the incidence of LAC in a northern Chinese (Beijing) population and monitored survival.
Methods: A prospective registry population‐based study was conducted over a 6‐year period in a general, unselected, and representative community in Beijing with approximately 100 000 long‐term permanent residents. All first‐ever stroke cases were registered.
Results: A total of 1184 patients with ischaemic stroke were identified; 36.9% (437 cases) were classified as LAC. Age‐standardized incidence rates of LAC ranged from 24.0 to 51.3/100 000 with an average rate of 35.3/100 000 during study period. The incidence of LAC increased with age before 70 years. The incidence of non‐LAC increased with age. There were no significant differences in crude incidence of LAC between men and women (78.4/100 000 vs. 75.4/100 000). The incidence of non‐LAC was significantly higher in men than in women (155/100 000 vs. 107/100 000, P < 0.001). The 28‐day case fatality proportions were significantly lower in patients with LAC (0.5%) versus non‐LAC (14.9%). One year after acute stroke onset, the survival rates between LAC and non‐LAC were similar.
Conclusion: LAC is a common stroke subtype in Northern China. Men or the elderly are more likely to have non‐LAC. Long‐term survival following LAC is similar to non‐LAC patients.
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The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, ...located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the "roof of the world" and the antiquity of human high-altitude occupations more generally.
A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest ...iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.
Objectives
We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese.
Methods
The telomere restriction fragment (TRF) length of leukocytes in ...the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed.
Results
Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function.
Conclusion
The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.
The edible mushroom Termitomyces is an agaric‐type basidiomycete fungus that has a symbiotic relationship with fungus‐growing termites. An understanding of the detailed development mechanisms ...underlying the adaptive responses of Termitomyces sp. to their growing environment is lacking. Here, we compared the transcriptome sequences of different Termitomyces sp. samples and link‐stipe grown on fungus combs in situ and monocultured in vitro. The assembled reads generated 8052 unigenes. The expression profiles were highly different for 2556 differentially expressed genes (DEGs) of the treated samples, where the expression of 1312 and 1244 DEGs was upregulated in the Mycelium and link‐stipe groups respectively. Functional classification of the DEGs based on both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed an expected shift in fungal gene expression, where stress response genes whose expression was upregulated in link‐stipe may adaptively be involved in cell wall hydrolysis and fusion, pathogenesis, oxidation‐reduction, transporter efflux, transposon efflux and self/non–self‐recognition. Urease has implications in the expression of genes involved in the nitrogen metabolism pathway, and its expression could be controlled by low‐level nitrogen fixation of fungus combs. In addition, the expression patterns of eleven select genes on the basis of qRT‐PCR were consistent with their changes in transcript abundance, as revealed by RNA sequencing. Taken together, these findings may be useful for enriching the knowledge concerning the Termitomyces adaptive response to in situ fungus combs compared with the response of monocultures in vitro.
Significance and Impact of the Study: The first study of the gene regulation from transcriptome can provide a theoretical basis for the subsequent further excavation of key developmental functional genes of Termitomyces sp. We found an important but not yet biologically defined Termitomyces tissue, link‐stipe. There are a lot of important developmental genes and stress response genes in the link‐stipe tissue, which can provide an important reference to analyse the development mechanism of Termitomyces sp. The important cohesion of link‐stipe tissue in the whole symbiotic system is demonstrated.
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