Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys

Objective To assess the acceptability of pre-pandemic influenza vaccination among healthcare workers in public hospitals in Hong Kong and the effect of escalation in the World Health Organization’s alert level for an influenza pandemic

p21-Activated Kinases 1, 2 and 4 in Endometrial Cancers: Effects on Clinical Outcomes and Cell Proliferation

p21-activated kinases (Paks) are serine/threonine protein kinases involved in biological events linked to malignant tumor progression. In this study, expression of Pak1, p-Pak2 Ser20, Pak4, pPak4 Ser474 in 21 normal endometrium, 16 hyperplastic endometrium without atypia, 17 atypical complex hyperplasia and 67 endometrial cancers was assessed by immunohistochemistry and correlated with clinicopathological parameters. We also accessed the proliferative role and downstream targets of Pak1 in endometrial cancer. Pak1 was expressed in cytoplasm whereas Pak4 and p-Pak4 were expressed in both cytoplasm and nucleus of endometrial tissues. In normal endometrium, significantly higher Pak1 (P = 0.028) and cytoplasmic p-Pak2 (P = 0.048) expression was detected in proliferative endometrium than secretory endometrium. Pak1, cytoplasmic and nuclear Pak4 and nuclear p-Pak4 was significantly overexpressed in endometrial cancer when compared to atrophic endometrium (all P<0.05). Moreover, type I endometrioid carcinomas showed significantly higher Pak1 expression than type II non-endometrioid carcinomas (P<0.001). On the other hand, Pak1, Pak4 and p-Pak4 expression negatively correlated with histological grade (all P<0.05) while p-Pak2 and cytoplasmic Pak4 expression inversely correlated with myometrial invasion (all P<0.05). Furthermore, patients with endometrial cancers with lower cytoplasmic Pak4 expression showed poorer survival (P = 0.026). Multivariate analysis showed cytoplasmic Pak4 is an independent prognostic factor. Functionally, knockdown of Pak1, but not Pak4, in endometrial cancer cell line led to reduced cell proliferation along with reduced cyclin D1, estrogen receptor (ERα) and progestogen receptor (PR) expression. Significant correlation between Pak1 and PR expression was also detected in clinical samples. Our findings suggest that Pak1 and cytoplasmic p-Pak2 may promote cell proliferation in normal endometrium during menstral cycle. Pak1, cytoplasmic and nuclear Pak4 and nuclear p-Pak4 are involved in the pathogenesis of endometrial cancer especially in postmenopausal women. Pak1 promote endometrial cancer cell proliferation, particular in type I endometrioid carcinoma. Cytoplasmic Pak4 can be potential prognostic marker in endometrial cancer.published_or_final_versio

Measurement of Cosmic-ray Muons and Muon-induced Neutrons in the Aberdeen Tunnel Underground Laboratory

We have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for tracking the incident cosmic-ray muons and 760 L of gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be $I_{\mu} = (5.7 \pm 0.6) \times 10^{-6}$ cm$^{-2}$s$^{-1}$sr$^{-1}$. The yield of muon-induced neutrons in the liquid scintillator was determined to be $Y_{n} = (1.19 \pm 0.08 (stat) \pm 0.21 (syst)) \times 10^{-4}$ neutrons/($\mu\cdot$g$\cdot$cm$^{-2}$). A fit to the recently measured neutron yields at different depths gave a mean muon energy dependence of $\left\langle E_{\mu} \right\rangle^{0.76 \pm 0.03}$ for liquid-scintillator targets.Comment: 14 pages, 17 figures, 3 table

High-frequency dynamics of type-B glass formers investigated by broadband dielectric spectroscopy

We present the results of broadband dielectric spectroscopy on two glass formers with strong Johari-Goldstein beta-relaxations. In addition to the alpha- and beta-relaxation dynamics, the extension of the spectra up to 1 THz also allows revealing information on the fast beta-process in this class of materials. There is clear evidence for a fast process contributing in the region of the high-frequency loss minimum, which is analyzed in terms of the idealized mode-coupling theory.Comment: 7 pages, 5 figure

Cytokine Response Patterns in Severe Pandemic 2009 H1N1 and Seasonal Influenza among Hospitalized Adults

BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1) influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation). Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years), and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%), although severe pneumonia with hypoxemia (54.0% vs 28.3%) and ICU admissions (25.4% vs 1.9%) were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal) and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17)-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01). This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10)unit increase; P = 0.002), and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01) in influenza infections. PBMCs in seasonal influenza patients were activated and expressed cytokines ex vivo (e.g. IL-6, CXCL8/IL-8, CCL2/MCP-1, CXCL10/IP-10, CXCL9/MIG); their 'responsiveness' to stimuli was shown to change dynamically during the illness course. CONCLUSIONS: A hyperactivated proinflammatory, but suppressed adaptive-immunity (Th1/Th17)-related cytokine response pattern was found in severe pH1N1 pneumonia, different from seasonal influenza. Cytokine/immune-dysregulation may be important in its pathogenesis

Sex tourism among Chinese men who have sex with men: a cross-sectional observational study

Abstract Background Sex tourism among men who have sex with men (MSM) may exacerbate transmission of HIV and other sexually transmitted infections (STIs). Sex tourism is defined as purchasing sex with gifts or money outside of one’s hometown. Our objective was to characterize the frequency, socio-demographic characteristics, and sexual risk behaviors among Chinese MSM sex tourists. Methods An online, cross-sectional survey for high-risk MSM throughout China was conducted in November 2015 covering sociodemographic characteristics, sexual risk behaviors, and sex tourism. Univariate and multivariable logistic regressions were performed to identify correlates of sex tourism. The mean MSM HIV prevalence of sex tourism journey origins and destinations were compared. Results Of 1189 MSM who completed the survey, 62 (5%) men identified as sex tourists; among these sex tourists, twenty (32%) traveled primarily to purchase sex and the remainder purchased sex while traveling for another purpose. There was minimal socio-demographic and behavioral difference between the two groups. In multivariable analyses, adjusting for age and income, sex tourism was correlated with high-risk sexual behaviors, higher income (aOR 4.44, 95%CI 1.77–11.18) and living with HIV (aOR 2.79, 95%CI 1.03–7.55). Sex tourism was more often from locations with lower to higher MSM HIV prevalence (mean = 4.47, SD = 2.01 versus mean = 6.86, SD = 5.24). Conclusion MSM sex tourists were more likely to have risky sexual behaviors and travel to locations with a higher HIV prevalence. MSM sex tourists may be part of core groups that are disproportionately responsible for MSM HIV transmission. Enhanced surveillance and interventions tailored to MSM sex tourists should be considered

Broadband Dielectric Spectroscopy on Glass-Forming Propylene Carbonate

Dielectric spectroscopy covering more than 18 decades of frequency has been performed on propylene carbonate in its liquid and supercooled-liquid state. Using quasi-optic submillimeter and far-infrared spectroscopy the dielectric response was investigated up to frequencies well into the microscopic regime. We discuss the alpha-process whose characteristic timescale is observed over 14 decades of frequency and the excess wing showing up at frequencies some three decades above the peak frequency. Special attention is given to the high-frequency response of the dielectric loss in the crossover regime between alpha-peak and boson-peak. Similar to our previous results in other glass forming materials we find evidence for additional processes in the crossover regime. However, significant differences concerning the spectral form at high frequencies are found. We compare our results to the susceptibilities obtained from light scattering and to the predictions of various models of the glass transition.Comment: 13 pages, 9 figures, submitted to Phys. Rev.

Millipede genomes reveal unique adaptations during myriapod evolution

This is the final version. Available from Public Library of Science via the DOI in this record.The final genome assemblies have been deposited to NCBI database with accession numbers JAAFCF000000000 and JAAFCE000000000. The mRNA and sRNA transcriptomic data generated in this study have been deposited to the NCBI database under the following BioProject accessions: PRJNA564202 (Helicorthomorpha holstii) and PRJNA564195 (Trigoniulus corallinus).The Myriapoda, composed of millipedes and centipedes, is a fascinating but poorly understood branch of life, including species with a highly unusual body plan and a range of unique adaptations to their environment. Here, we sequenced and assembled 2 chromosomal-level genomes of the millipedes Helicorthomorpha holstii (assembly size = 182 Mb; shortest scaffold/contig length needed to cover 50% of the genome [N50] = 18.11 Mb mainly on 8 pseudomolecules) and Trigoniulus corallinus (assembly size = 449 Mb, N50 = 26.78 Mb mainly on 17 pseudomolecules). Unique genomic features, patterns of gene regulation, and defence systems in millipedes, not observed in other arthropods, are revealed. Both repeat content and intron size are major contributors to the observed differences in millipede genome size. Tight Hox and the first loose ecdysozoan ParaHox homeobox clusters are identified, and a myriapod-specific genomic rearrangement including Hox3 is also observed. The Argonaute (AGO) proteins for loading small RNAs are duplicated in both millipedes, but unlike in insects, an AGO duplicate has become a pseudogene. Evidence of post-transcriptional modification in small RNAs-including species-specific microRNA arm switching-providing differential gene regulation is also obtained. Millipedes possesses a unique ozadene defensive gland unlike the venomous forcipules found in centipedes. We identify sets of genes associated with the ozadene that play roles in chemical defence as well as antimicrobial activity. Macro-synteny analyses revealed highly conserved genomic blocks between the 2 millipedes and deuterostomes. Collectively, our analyses of millipede genomes reveal that a series of unique adaptations have occurred in this major lineage of arthropod diversity. The 2 high-quality millipede genomes provided here shed new light on the conserved and lineage-specific features of millipedes and centipedes. These findings demonstrate the importance of the consideration of both centipede and millipede genomes-and in particular the reconstruction of the myriapod ancestral situation-for future research to improve understanding of arthropod evolution, and animal evolutionary genomics more widely.Hong Kong Research Grants Council (RGC) General Research FundHong Kong Research Grants Council (RGC) General Research FundThe Chinese University of Hong Kong (CUHK

Bench to Bed Evidences for Pharmacokinetic and Pharmacodynamic Interactions Involving Oseltamivir and Chinese Medicine

Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although Cmax, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P<0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P<0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe