Antibody responses to lytic and latent human herpesvirus 8 antigens among HIV-infected patients in central China

Human herpesvirus 8 (HHV8) is an important opportunistic infection of HIV/AIDS. However, very little is known about antibody seropositivities to HHV8 lytic and latent antigens among HIVinfected patients in China. Therefore, a cross-sectional study was conducted to explore HHV8 serostatus among 316 HIV-infected patients in a rural area of central China. The antibody seropositivity to HHV8 ORF65 (lytic) and LANA (latent) antigens was 12.7% and 10.4%, respectively. Patients who were naïve to antiretroviral therapy (ART) were more likely to be seropositive for antibodies to ORF65 (OR: 3.79; 95% CI: 1.71–8.42) and LANA (OR: 3.77; 95% CI: 1.55–9.14) than patients receiving ART. Patients having CD4+ cell counts less than 200 cells/mm3 were more likely to be seropositive for LANA antibody (OR: 3.53; 95% CI: 1.44–8.64) and to have lower LANA antibody titer (p = 0.007). They were also more likely to be seropositive for ORF65 antibody (OR: 2.12; 95% CI: 0.94–4.78) and to have a lower ORF65 antibody titer (p = 0.065), though the difference was marginally significant. No associations between other viral coinfections studied and antibody seropositivity to either latent or lytic HHV8 antigens were identified. Study findings suggest that antibody responses to both lytic and latent HHV8 antigens among HIV patients in China were fairly high and were associated with immunodeficiency status and ART

Changing Patterns of Spatial Clustering of Schistosomiasis in Southwest China between 1999–2001 and 2007–2008: Assessing Progress toward Eradication after the World Bank Loan Project

We compared changes in the spatial clustering of schistosomiasis in Southwest China at the conclusion of and six years following the end of the World Bank Loan Project (WBLP), the control strategy of which was focused on the large-scale use of chemotherapy. Parasitological data were obtained through standardized surveys conducted in 1999–2001 and again in 2007–2008. Two alternate spatial cluster methods were used to identify spatial clusters of cases: Anselin’s Local Moran’s I test and Kulldorff’s spatial scan statistic. Substantial reductions in the burden of schistosomiasis were found after the end of the WBLP, but the spatial extent of schistosomiasis was not reduced across the study area. Spatial clusters continued to occur in three regions: Chengdu Plain, Yangtze River Valley, and Lancang River Valley during the two periods, and regularly involved five counties. These findings suggest that despite impressive reductions in burden, the hilly and mountainous regions of Southwest China remain at risk of schistosome re-emergence. Our results help to highlight specific locations where integrated control programs can focus to speed the elimination of schistosomiasis in China

Is a highly pathogenic avian influenza virus H5N1 fragment recombined in PB1 the key for the epidemic of the novel AIV H7N9 in China, 2013?

SummaryBackgroundA novel avian influenza A H7N9 virus that infects humans was identified in China in 2013. This study is the first to comprehensively investigate the characteristics of genomic recombination, rather than reassortment, which has been the subject of investigation in previously reported studies.MethodsNovel avian influenza virus (AIV) H7N9 genome sequences were obtained from the NCBI Influenza Virus Sequence Database and the Global Initiative on Sharing Avian Influenza Database (GISAID) and a representative isolate was subjected to homogeneity analysis. A phylogenetic tree was constructed. Eight segments of the isolate were analyzed to identify segments with recombination events, the corresponding recombination fragments, and breakpoints. The evolutionary history of the recombined fragments was tracked by constructing phylogenetic trees of the recombination fragments.ResultsAmong the eight segments of the novel AIV H7N9 analyzed, only the PB1 segment showed a marked recombination phenomenon, with 11 recombination events; these included five actual recombination events and six possible misalignment artifact recombination events. The most notable was the recombination of a 291-nucleotide (nt) fragment at the 490–780 nt site that was affiliated to a highly pathogenic avian influenza virus (HPAIV) H5N1 (A/tree sparrow/Thailand/VSMU-16-RBR/2005). The phylogenetic tree of the 291-nt recombination fragment on the PB1 segment showed that the novel AIV H7N9 had a close genetic relationship to H9N2 and H5N1.ConclusionsThe novel AIV H7N9 might have reassorted its PB1 segment from H9N2 circulating in China, and this H9N2 PB1 might have been recombined into a highly pathogenic fragment from HPAIV H5N1, which could be the reason for the high fatality rate among patients with AIV H7N9 influenza

The epidemiology of hospitalized influenza in children, a two year population-based study in the People's Republic of China

<p>Abstract</p> <p>Background</p> <p>The epidemiology and disease burden of annual influenza in children in mainland People's Republic of China have not been reported in detail. To understand the incidence and epidemiology of laboratory-proven influenza hospitalization in children in China, a review of available laboratory and hospital admission data was undertaken.</p> <p>Methods</p> <p>We conducted a retrospective population-based study in Suzhou and the surrounding area of Jiangsu province, China for hospitalized cases of respiratory illness at Suzhou Children's Hospital. Cases of pneumonia or respiratory illness were identified from hospital computer data bases. Routine virological testing by fluorescent monoclonal antibody assay of all hospitalized children identified influenza and other viruses. We calculated incidence rates using census population denominators.</p> <p>Results</p> <p>Of 7,789 specimens obtained during 2007 and 2008, 85 were positive for influenza A and 25 for influenza B. There were 282 specimens with parainfluenza virus and 1392 with RSV. Influenza occurred throughout the year, with peaks in the winter, and in August/September. Overall estimated annual incidence of laboratory-proven influenza hospitalization was 23-27/100,000 children 0-4 years old, and 60/100,000 in infants 0-6 months, with an average hospitalization of 9 days.</p> <p>Conclusions</p> <p>Influenza disease in young children in this part of China is a relatively common cause of hospitalization, and occurs throughout the year. The use of influenza vaccine in Chinese children has the potential to reduce the effect of influenza in the children, as well as in their communities. Studies are needed to further assess the burden of influenza, and to develop and refine effective strategies of immunization of young children in China.</p

Nonparametric Evaluation of Dynamic Disease Risk: A Spatio-Temporal Kernel Approach

Quantifying the distributions of disease risk in space and time jointly is a key element for understanding spatio-temporal phenomena while also having the potential to enhance our understanding of epidemiologic trajectories. However, most studies to date have neglected time dimension and focus instead on the “average” spatial pattern of disease risk, thereby masking time trajectories of disease risk. In this study we propose a new idea titled “spatio-temporal kernel density estimation (stKDE)” that employs hybrid kernel (i.e., weight) functions to evaluate the spatio-temporal disease risks. This approach not only can make full use of sample data but also “borrows” information in a particular manner from neighboring points both in space and time via appropriate choice of kernel functions. Monte Carlo simulations show that the proposed method performs substantially better than the traditional (i.e., frequency-based) kernel density estimation (trKDE) which has been used in applied settings while two illustrative examples demonstrate that the proposed approach can yield superior results compared to the popular trKDE approach. In addition, there exist various possibilities for improving and extending this method

Case report: Sequential therapy with dupilumab and baricitinib for severe alopecia areata with atopic dermatitis in children

An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period

Histone acetyltransferase inhibitors antagonize AMP-activated protein kinase in postmortem glycolysis

Objective The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK) activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. Methods A total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR, a specific activator of AMPK), AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II) and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases). After mice were euthanized, the Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured. Results Activation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. At the same time, it increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis. Several bands of proteins were detected to be differentially acetylated in muscle with different glycolytic rates. Conclusion Protein acetylation plays an important regulatory role in postmortem glycolysis. As AMPK mediates the effects of pre-slaughter stress on postmortem glycolysis, protein acetylation is likely a mechanism by which antemortem stress influenced postmortem metabolism and meat quality though the exact mechanism is to be elucidated

Genetic Variation At 8Q24, Family History Of Cancer, And Upper Gastrointestinal Cancers In A Chinese Population

Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95% confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (ORadj 2.80; 95% CI 1.15–6.80). Heterogeneity was observed (Pheterogeneity=0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (ORadj 2.00; 95% CI 1.15–3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility

Perceived acceptable uncertainty regarding comparability of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment.

BACKGROUND Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown. OBJECTIVE To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers. METHODS A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results. RESULTS There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1-5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67). CONCLUSION Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT

Single Nucleotide Polymorphisms of 8 Inflammation-related Genes and their Associations with Smoking-related Cancers

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers. © 2010 UICC