Epidemiological characteristics of Pandemic Influenza A (H1N1-2009) in Zhanjiang, China

Background: A novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in Zhanjiang, China. Methods: The case and outbreak reports of influenza-like illness (ILI) were collected from the Chinese information system of disease control and prevention and the influenza surveillance system of Zhanjiang city. Real-time RT-PCR was conducted, and epidemic and virological characteristics of the virus were analyzed using descriptive epidemiological methods and Chi-square trend tests. Results: A total of 276 reported cases were confirmed from July 16, 2009 to June 30, 2010. The attack rate of outbreak was from 1.1% to 6.0%. The disease peak occurred in December 2009, after which the outbreak subsided gradually. The last case was confirmed in April 2010. Conclusion: The main population struck by the H1N1-2009 virus was young adults, youths and children. The outbreaks most frequently occurred in schools, and most cases were acquired locally

Characterization of volatile organic compounds at a roadside environment in Hong Kong: An investigation of influences after air pollution control strategies

Vehicular emission is one of the important anthropogenic pollution sources for volatile organic compounds (VOCs). Four characterization campaigns were conducted at a representative urban roadside environment in Hong Kong between May 2011 and February 2012. Carbon monoxide (CO) and VOCs including methane (CH4), non-methane hydrocarbons (NMHCs), halocarbons, and alkyl nitrates were quantified. Both mixing ratios and compositions of the target VOCs show ignorable seasonal variations. Except CO, liquefied petroleum gas (LPG) tracers of propane, i-butane and n-butane are the three most abundant VOCs, which increased significantly as compared with the data measured at the same location in 2003. Meanwhile, the mixing ratios of diesel- and gasoline tracers such as ethyne, alkenes, aromatics, halogenated, and nitrated hydrocarbons decreased by at least of 37%. The application of advanced multivariate receptor modeling technique of positive matrix factorization (PMF) evidenced that the LPG fuel consumption is the largest pollution source, accounting for 60 ± 5% of the total quantified VOCs at the roadside location. The sum of ozone formation potential (OFP) for the target VOCs was 300.9 μg-O3 m-3, which was 47% lower than the value of 567.3 μg-O3 m-3 measured in 2003. The utilization of LPG as fuel in public transport (i.e., taxis and mini-buses) contributed 51% of the sum of OFP, significantly higher than the contributions from gasoline- (16%) and diesel-fueled (12%) engine emissions. Our results demonstrated the effectiveness of the switch from diesel to LPG-fueled engine for taxis and mini-buses implemented by the Hong Kong Special Administrative Region (HKSAR) Government between the recent ten years, in additional to the execution of substitution to LPG-fueled engine and restrictions of the vehicular emissions in compliance with the updated European emission standards

Topical Diclofenac Solution for Osteoarthritis of the Knee: An Updated Meta-Analysis of Randomized Controlled Trials.

This study was performed to assess the efficacy and safety of a topical diclofenac solution in patients with knee osteoarthritis (OA). PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases were searched for randomized controlled trials until June 2020. The WOMAC pain, stiffness, physical function subscales, pain on walking, and the occurrence of adverse events were pooled to comprehensively analyse the efficacy and safety of topical diclofenac solution. All statistical analyses were conducted using Review Manager 5.3 software. Five RCTs were included, which provided high-quality evidence. In comparison to the vehicle control, the mean differences for WOMAC pain, stiffness, and physical function subscales, as well as pain on walking, were all statistically significant in favor of topical diclofenac solution. The safety of topical diclofenac solution was similar to the vehicle control, apart from adverse events involving application-site skin reactions. Topical diclofenac solution is effective and safe for use in patients with knee OA, but may cause minor skin reactions

Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning

The spatial regulation of combinatorial expression of Hox genes is critical for determining hindbrain rhombomere (r) identities. To address the cross-regulatory relationship between Hox genes in hindbrain neuronal specification, we have generated a gain-of-function transgenic mouse mutant Hoxb3 Tg using the Hoxb2 r4-specific enhancer element. Interestingly, in r4 of the Hoxb3 Tg mutant where Hoxb3 was ectopically expressed, the expression of Hoxb1 was specifically abolished. The hindbrain neuronal defects of the Hoxb3 Tg mutant mice were similar to those of Hoxb1 -/- mutants. Therefore, we hypothesized that Hoxb3 could directly suppress Hoxb1 expression. We first identified a novel Hoxb3 binding site S3 on the Hoxb1 locus and confirmed protein binding to this site by EMSA, and by in vivo ChIP analysis using P19 cells and hindbrain tissues from the Hoxb3 Tg mutant. We further showed that Hoxb3 could suppress Hoxb1 transcriptional activity by chick in ovo luciferase reporter assay. Moreover, in E10.5 wildtype caudal hindbrain, where Hoxb1 is not expressed, we showed by in vivo ChIP that Hoxb3 was consistently bound to the S3 site on the Hoxb1 gene. This study reveals a novel negative regulatory mechanism by which Hoxb3 as a posterior gene serves to restrict Hoxb1 expression in r4 by direct transcriptional repression to maintain the rhombomere identity. © 2011 Elsevier Inc.postprin

The experience of enchantment in human-computer interaction

Improving user experience is becoming something of a rallying call in human–computer interaction but experience is not a unitary thing. There are varieties of experiences, good and bad, and we need to characterise these varieties if we are to improve user experience. In this paper we argue that enchantment is a useful concept to facilitate closer relationships between people and technology. But enchantment is a complex concept in need of some clarification. So we explore how enchantment has been used in the discussions of technology and examine experiences of film and cell phones to see how enchantment with technology is possible. Based on these cases, we identify the sensibilities that help designers design for enchantment, including the specific sensuousness of a thing, senses of play, paradox and openness, and the potential for transformation. We use these to analyse digital jewellery in order to suggest how it can be made more enchanting. We conclude by relating enchantment to varieties of experience.</p

Administration of bisphosphonate for hypercalcemia associated with oral cancer

BACKGROUND: The efficacy of treating hypercalcemia with bisphosphonate (BP) in patients with advanced oral cancer has not been fully investigated. This retrospective study evaluated the clinical course of hypercalcemic patients with and without BP treatment. METHODS: Sixteen hypercalcemic patients, most of whom had uncontrollable locoregional lesions and lung metastases, were studied. Nine patients had been given BP, and the rest had not. RESULTS: There were significant differences in age and serum ALT between the BP-treated and -untreated groups. The first administration of BP effectively and safely decreased the serum calcium level, but repeated administrations were less effective. Although the patients treated with BP survived significantly longer than the untreated subjects, the difference of the median was only about 2 weeks. CONCLUSION: The occurrence of hypercalcemia in oral cancer patients apparently implies an extremely poor prognosis, and long-term survival cannot be expected, even with BP treatment

Differential effects of bile acids on the postprandial secretion of gut hormones: a randomized crossover study.

Bile acids (BA) regulate postprandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The postprandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effects of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on postprandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon, and ghrelin. Twelve healthy volunteers underwent a mixed meal test 60 min after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg), or no BA in a randomized crossover study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin, and fibroblast growth factor 19 were measured prior to BA administration at -60 and 0 min (just prior to mixed meal) and 15, 30, 60, 120, 180, and 240 min after the meal. UDCA and CDCA provoked differential gut hormone responses; UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced postprandial secretion of GIP, with an associated reduction in postprandial insulin secretion. Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmed in obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions. NEW & NOTEWORTHY: Oral CDCA and UDCA have different effects on gut and pancreatic hormone secretion. A single dose of CDCA increased fasting secretion of the hormones GLP-1 and OXM with an accompanying increase in insulin secretion. CDCA also reduced postprandial GIP secretion, which was associated with reduced insulin. In contrast, UDCA did not change gut hormone secretion fasting or postprandially. Oral CDCA could be beneficial to patients with obesity and diabetes

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

The combination of gefitinib and RAD001 inhibits growth of HER2 overexpressing breast cancer cells and tumors irrespective of trastuzumab sensitivity

<p>Abstract</p> <p>Background</p> <p>HER2-positive breast cancers exhibit high rates of innate and acquired resistance to trastuzumab (TZ), a HER2-directed antibody used as a first line treatment for this disease. TZ resistance may in part be mediated by frequent co-expression of EGFR and by sustained activation of the mammalian target of rapamycin (mTOR) pathway. Here, we assessed feasibility of combining the EGFR inhibitor gefitinib and the mTOR inhibitor everolimus (RAD001) for treating HER2 overexpressing breast cancers with different sensitivity to TZ.</p> <p>Methods</p> <p>The gefitinib and RAD001 combination was broadly evaluated in TZ sensitive (SKBR3 and MCF7-HER2) and TZ resistant (JIMT-1) breast cancer models. The effects on cell growth were measured in cell based assays using the fixed molar ratio design and the median effect principle. <it>In vivo </it>studies were performed in Rag2M mice bearing established tumors. Analysis of cell cycle, changes in targeted signaling pathways and tumor characteristics were conducted to assess gefitinib and RAD001 interactions.</p> <p>Results</p> <p>The gefitinib and RAD001 combination inhibited cell growth <it>in vitro </it>in a synergistic fashion as defined by the Chou and Talalay median effect principle and increased tumor xenograft growth delay. The improvement in therapeutic efficacy by the combination was associated <it>in vitro </it>with cell line dependent increases in cytotoxicity and cytostasis while treatment <it>in vivo </it>promoted cytostasis. The most striking and consistent therapeutic effect of the combination was increased inhibition of the mTOR pathway (<it>in vitro </it>and <it>in vivo</it>) and EGFR signaling <it>in vivo </it>relative to the single drugs.</p> <p>Conclusions</p> <p>The gefitinib and RAD001 combination provides effective control over growth of HER2 overexpressing cells and tumors irrespective of the TZ sensitivity status.</p

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas