Epidemiological and virological characteristics of pandemic influenza A (H1N1) 2009 in school outbreaks in China

Background: During the 2009 pandemic influenza H1N1 (2009) virus (pH1N1) outbreak, school students were at an increased risk of infection by the pH1N1 virus. However, the estimation of the attack rate showed significant variability. Methods: Two school outbreaks were investigated in this study. A questionnaire was designed to collect information by interview. Throat samples were collected from all the subjects in this study 6 times and sero samples 3 times to confirm the infection and to determine viral shedding. Data analysis was performed using the software STATA 9.0. Findings: The attack rate of the pH1N1 outbreak was 58.3% for the primary school, and 52.9% for the middle school. The asymptomatic infection rates of the two schools were 35.8% and 37.6% respectively. Peak virus shedding occurred on the day of ARI symptoms onset, followed by a steady decrease over subsequent days (p = 0.026). No difference was found either in viral shedding or HI titer between the symptomatic and the asymptomatic infectious groups. Conclusions: School children were found to be at a high risk of infection by the novel virus. This may be because of a heightened risk of transmission owing to increased mixing at boarding school, or a lack of immunity owing to socioeconomic status. We conclude that asymptomatically infectious cases may play an important role in transmission of the pH1N1 virus

Thrombin-induced CCN2 expression as a target for anti-fibrotic therapy in scleroderma

Scleroderma (systemic sclerosis, SSc) is a fibrotic disease for which there is no therapy. CCN2 (connective tissue growth factor, CTGF) is a marker and mediator of fibrosis. Previously, it has been shown that thrombin induces CCN2 expression in fibroblasts. In a recent fascinating report, Bogatkevich et al. (Arthritis Rheum 60:3455–3464, 2009) show that dabigatran, an inhibitor of thrombin action, blocks the overexpression of CCN2 by scleroderma fibroblasts and reverses the contractile phenotype of these cells. These results strongly suggest that dabigatran may be a potential antifibrotic drug for the treatment of fibrosing diseases such as scleroderma

Gingival Fibroblasts Display Reduced Adhesion and Spreading on Extracellular Matrix: A Possible Basis for Scarless Tissue Repair?

Unlike skin, oral gingiva do not scar in response to injury. The basis of this difference is likely to be revealed by comparing the responses of dermal and gingival fibroblasts to fibrogenic stimuli. Previously, we showed that, compared to dermal fibroblasts, gingival fibroblasts are less responsive to the potent pro-fibrotic cytokine TGFβ, due to a reduced production of endothelin-1 (ET-1). In this report, we show that, compared to dermal fibroblasts, human gingival fibroblasts show reduced expression of pro-adhesive mRNAs and proteins including integrins α2 and α4 and focal adhesion kinase (FAK). Consistent with these observations, gingival fibroblasts are less able to adhere to and spread on both fibronectin and type I collagen. Moreover, the enhanced production of ET-1 mRNA and protein in dermal fibroblasts is reduced by the FAK/src inhibitor PP2. Given our previous observations suggesting that fibrotic fibroblasts display elevated adhesive properties, our data suggest that scarring potential may be based, at least in part, on differences in adhesive properties among fibroblasts resident in connective tissue. Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury

Connective tissue growth factor is induced in bleomycin-induced skin scleroderma

The origin of fibrotic cells within connective tissue is unclear. For example, the extent to which microvascular pericytes contribute to the number of myofibroblasts present in dermal fibrosis in uncertain. Connective tissue growth factor (CTGF/CCN2) is a marker and mediator of fibrosis. In this report, we use an antibody recognizing CCN2 to assess the cell types in mouse dermis which express CCN2 in the bleomycin model of skin scleroderma. Control (PBS injected) and fibrotic (bleomycin-injected) dermis was examined for CCN2, α-smooth muscle actin (α-SMA) (to detect myofibroblasts), and NG2 (to detect pericytes) expression. Consistent with previously published data, CCN2 expression was largely absent in the dermis of control mice. However, upon exposure to bleomycin, CCN2 was observed in the dermis. Cells that expressed CCN2 were α−SMA-expressing myofibroblasts. Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis. Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction. Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma

Evaluating the impact of decentralising tuberculosis microscopy services to rural township hospitals in gansu province, china

<p>Abstract</p> <p>Background</p> <p>In 2004, the Ministry of Health issued the policy of decentralising microscopy services (MCs) to one third of all township hospitals in China. The study was conducted in Gansu Province, a poor western one in China. Ganzhou was one county in Gansu Province. Ganzhou County was identified as a unique case of further decentralisation of tuberculosis (TB) treatment services in township hospitals. The study evaluated the impact of the MC policy on providers and patients in Gansu Province. The second objective was to assess the unique case of Ganzhou County compared with other counties in the province.</p> <p>Methods</p> <p>Both quantitative and qualitative methods were used. All 523 MCs in the province completed an institutional survey regarding their performance. Four counties were selected for in-depth investigation, where 169 TB suspects were randomly selected from the MC and county TB dispensary registers for questionnaire surveys. Informant interviews were conducted with 38 health staff at the township and county levels in the four counties.</p> <p>Results</p> <p>Gansu established MCs in 39% of its township hospitals. From January 2006 to June 2007, 8% of MCs identified more than 10 TB sputum smear positive patients while 54% did not find any. MCs identified 1546 TB sputum smear positive patients, accounting for 9% of the total in the province. The throughputs of MCs in Ganzhou County were eight times of those in other counties. Interviews identified several barriers to implement the MC policy, such as inadequate health financing, low laboratory capacity, lack of human resources, poor treatment and management capacities, and lack of supervisions from county TB dispensaries.</p> <p>Conclusion</p> <p>Microscopy centre throughputs were generally low in Gansu Province, and the contribution of MCs to TB case detection was insignificant taking account the number of MCs established. As a unique case of full decentralisation of TB service, Ganzhou County presented better results. However, standards and quality of TB care needed to be improved. The MC policy needs to be reviewed in light of evidence from this study.</p

Stressing the Ubiquitin-Proteasome System without 20S Proteolytic Inhibition Selectively Kills Cervical Cancer Cells

Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their α-β unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation up-stream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine

Hot deformation behavior and processing maps of diamond/Cu composites

The hot deformation behaviors of 50 vol pct uncoated and Cr-coated diamond/Cu composites were investigated using hot isothermal compression tests under the temperature and strain rate ranging from 1073 K to 1273 K (800 C to 1000 C) and from 0.001 to 5 s1, respectively. Dynamic recrystallization was determined to be the primary restoration mechanism during deformation. The Cr3C2 coating enhanced the interfacial bonding and resulted in a larger flow stress for the Cr-coated diamond/Cu composites. Moreover, the enhanced interfacial affinity led to a higher activation energy for the Cr-coated diamond/Cu composites (238 kJ/mol) than for their uncoated counterparts (205 kJ/mol). The strain-rate-dependent constitutive equations of the diamond/Cu composites were derived based on the Arrhenius model, and a high correlation (R = 0.99) was observed between the calculated flow stresses and experimental data. With the help of processing maps, hot extrusions were realized at 1123 K/0.01 s1 and 1153 K/0.01 s1 (850 C/0.01 s1 and 880 C/0.01 s1) for the uncoated and coated diamond/Cu composites, respectively. The combination of interface optimization and hot extrusion led to increases of the density and thermal conductivity, thereby providing a promising route for the fabrication of diamond/Cu composites