Searching for Sharp Drops in the Incidence of Pandemic A/H1N1 Influenza by Single Year of Age

BACKGROUND During the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52-53 years old in 2009, but the precise range of ages affected has not been delineated. METHODS AND FINDINGS To test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951-1959 (hospitalized) and 1953-1960 (not hospitalized). CONCLUSIONS The reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957.The project described was supported by the National Institute Of General Medical Sciences [Award Number U54GM088558], http://www.nigms.nih. gov/. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of General Medical Sciences or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Searching for Sharp Drops in the Incidence of Pandemic A/H1N1 Influenza by Single Year of Age

Background: During the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52–53 years old in 2009, but the precise range of ages affected has not been delineated. Methods and Findings: To test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951–1959 (hospitalized) and 1953–1960 (not hospitalized). Conclusions: The reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957

Rejeito de barragem de min?rio de ferro na produ??o de ladrilhos hidr?ulicos : uma an?lise de valor para sustentabilidade de edifica??es.

The present work discloses the development of a sustainable cement tile (SCT) produced with Iron Ore Tailings from tailings dams (IOT). Initially, technical evaluation and environmental analysis of IOT were performed through physical, chemical and morphological characterisation, leaching and dissolution tests. Its feasibility as a pigment was also investigated. Subsequently, the value analysis was performed, starting from an empathy map to a study on environmental, social and emotional values in the relationship between people and product. As result, the IOT presented fine, crystalline particles, no toxicity, and is technically feasible to be employed as filler, aggregate and pigment in the production of SCT. The colour layer of the SCT presented more homogeneous colour and less pores than conventional ones. Therefore, the design of the SCT was developed, incorporating intangible values such as: environmental ideology, local identity and social expression. In this sense, the present work seeks to assist in the decision-making process involving IOT as construction material.O presente trabalho abrange o desenvolvimento de ladrilho hidr?ulico sustent?vel (LHS) produzido com rejeitos de barragem de min?rio de ferro (RBMF). Inicialmente, a avalia??o t?cnica e a an?lise ambiental do RBMF foram realizadas atrav?s de testes de caracteriza??o f?sica, qu?mica e morfol?gica, lixivia??o e dissolu??o. Sua viabilidade como pigmento tamb?m foi investigada. Posteriormente, a an?lise de valor foi realizada, partindo de um mapa de empatia at? o estudo sobre valores ambientais, sociais e emocionais na rela??o entre pessoas e produtos. Como resultado, o RBMF se apresentou como part?culas finas, cristalinas, sem toxicidade, sendo tecnicamente vi?vel para ser empregado como f?ler, agregado e pigmento na produ??o de LHS. A camada de cor do LHS apresentou cores mais homog?neas e menos poros do que as convencionais. Assim, o projeto do LHS foi desenvolvido, incorporando valores intang?veis como: ideologia ambiental, identidade local e express?o social. Nesse sentido, o presente trabalho busca ajudar nas tomadas de decis?o envolvendo RBMF como material de constru??o

A single-tube allele specific-polymerase chain reaction to detect T315I resistant mutation in chronic myeloid leukemia patients

<p>Abstract</p> <p>Background</p> <p><it>BCR-ABL </it>kinase domain (KD) mutation is the major mechanism contributing to suboptimal response to tyrosine kinase inhibitors (TKI) in <it>BCR-ABL</it>-positive chronic myeloid leukemia (CML) patients. T315I mutation, as one of the most frequent KD mutations, has been shown to be strongly associated with TKI resistance and subsequent therapeutic failure. A simple and sensitive method is thus required to detect T315I mutation at the earliest stage.</p> <p>Methods</p> <p>A single-tube allele specific-polymerase chain reaction (AS-PCR) method was developed to detect T315I mutation in a mixture of normal and mutant alleles of varying dilutions. Denaturing high performance liquid chromatography (DHPLC) and direct sequencing were performed as a comparison to AS-PCR.</p> <p>Results</p> <p>T315I mutant bands were observed in the mixtures containing as low as 0.5-1% of mutant alleles by AS-PCR. The detection sensitivity of DHPLC was around 1.5-3% dilution whereas sequencing analysis was unable to detect below 6.25% dilution.</p> <p>Conclusion</p> <p>A single-tube AS-PCR is a rapid and sensitive screening method for T315I mutation. Detection of the most resistant leukemic clone in CML patients undergoing TKI therapy should be feasible with this simple and inexpensive method.</p

Searching for sharp drops in the incidence of pandemic A/H1N1 Influenza by single year of age

Fil: Hartman Jacobs, Jessica. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.Fil: Archer, Brett Nicholas. National Health Laboratory Service. National Institute for Communicable Diseases; Sudáfrica.Fil: Baker, Michael G. University of Otago. Department of Public Health; Nueva Zelanda.Fil: Cowling, Benjamin J. The University of Hong Kong. School of Public Health; China.Fil: Heffernan, Richard T. Wisconsin Department of Health Services. Division of Public Health; Estados Unidos.Fil. Mercer, Geoff. Australian National University. National Centre for Epidemiology and Population Health; Australia.Fil: Uez, Osvaldo. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Epidemiología; Argentina.Fil: Hanshaoworakul, Wanna. Ministry of Public Health. Department of Disease Control; Tailandia.Fil: Viboud, Cécile. National Institutes of Health. Division of International Epidemiology and Population Studies; Estados Unidos.Fil: Schwartz, Joel. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.Fil: Tchetgen Tchetgen, Eric. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.Fil: Lipsitch, Marc. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.BackgroundDuring the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52–53 years old in 2009, but the precise range of ages affected has not been delineated.Methods and FindingsTo test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951–1959 (hospitalized) and 1953–1960 (not hospitalized).ConclusionsThe reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957

Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro

<p>Abstract</p> <p>Background</p> <p>Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro.</p> <p>Methods</p> <p>Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC₅₀(concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated.</p> <p>Results</p> <p>The extracts from seven plant species (<it>Atractylodes lancea</it>, <it>Kaempferia galangal</it>, <it>Zingiber officinal</it>, <it>Piper chaba</it>, <it>Mesua ferrea</it>, <it>Ligusticum sinense</it>, <it>Mimusops elengi</it>) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (<it>Atractylodes lancea</it>, <it>Kaempferia galangal</it>, <it>Zingiber officinal</it>, <it>Piper chaba</it>, <it>Mesua ferrea</it>, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC₅₀values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC₅₀ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC₅₀ranged from 9.67 to 115.47 μg/ml. The only promising extract was from <it>Zingiber officinal </it>(IC₅₀= 9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC₅₀= 757 micromolar). The extract from <it>Atractylodes lancea </it>appears to be both the most potent and most selective against cholangiocarcinoma (IC₅₀= 24.09 μg/ml, SI = 8.6).</p> <p>Conclusions</p> <p>The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts.</p

Declining in efficacy of a three-day combination regimen of mefloquine-artesunate in a multi-drug resistance area along the Thai-Myanmar border

<p>Abstract</p> <p>Background</p> <p>Declining in clinical efficacy of artesunate-mefloquine combination has been documented in areas along the eastern border (Thai-Cambodian) of Thailand. In the present study, the clinical efficacy of the three-day combination regimen of artesunate-mefloquine as first-line treatment for acute uncomplicated falciparum malaria in Thailand was monitored in an area along the western border (Thai-Myanmar) of the country.</p> <p>Methods</p> <p>A total of 150 Burmese patients (85 males and 65 females) aged between 16 and 50 years who were attending the Mae Tao clinic, Mae-Sot, Tak Province, and presenting with symptomatic acute uncomplicated <it>Plasmodium falciparum </it>malaria were included into the study. Patients were treated initially (day 0) with 4 mg/kg body weight artesunate and 15 mg/kg body weight mefloquine. The dose regimen on day 2 was 4 mg/kg body weight artesunate and 10 mg/kg body weight mefloquine. On day 3, artesunate at the dose of 4 mg/kg body weight was given with 0.6 mg/kg body weight primaquine. Whole blood mefloquine and plasma artesunate and dihydroartemisinin (active plasma metabolite of artesunate) concentrations following treatment were determined by high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LCMS), respectively.</p> <p>Results</p> <p>Thirty-four cases had recrudescence during days 7 and 42. Five and 5 cases, respectively had reinfection with <it>P. falciparum </it>and reappearance of <it>Plasmodium vivax </it>in their peripheral blood during follow-up. The Kaplan-Meier estimate of the 42-and 28-day efficacy rates of this combination regimen were 72.58% (95% CI: 63.20-79.07%) and 83.06 (95% CI 76.14-94.40%), respectively. Parasite clearance time (PCT) and fever clearance time (FCT) were significantly prolonged in patients with treatment failure compared with those with sensitive response [median (95% CI) values for PCT 32.0 (20.0-48.0) <it>vs </it>24.0 (14.0-32.0) hr and FCT 30.0 (22.0-42.0) <it>vs </it>26.0 (18.0-36.0) hr; <it>p </it>< 0.005]. Whole blood mefloquine concentrations on days 1, 7 and 14 in patients with sensitive and recrudescence response were comparable. Although plasma concentration of dihydroartemisinin at 1 hour of treatment was significantly lower in patients with recrudescence compared with sensitive response [mean (95% CI) 456 (215-875) <it>vs </it>525 (452-599) ng/ml; <it>p </it>< 0.001], the proportion of patients with recrudescence who had relatively low (compared with the lower limit of 95% CI defined in the sensitive group) was significantly smaller than that of the sensitive group.</p> <p>Conclusions</p> <p>Although pharmacokinetic (ethnic-related) factors including resistance of <it>P. falciparum </it>to mefloquine contribute to some treatment failure following treatment with a three-day combination regimen of artesunate-mefloquine, results suggest that artesunate resistance may be emerging at the Thai-Myanmar border.</p

Characterization of a Novel Binding Protein for Fortilin/TCTP — Component of a Defense Mechanism against Viral Infection in Penaeus monodon

The Fortilin (also known as TCTP) in Penaeus monodon (PmFortilin) and Fortilin Binding Protein 1 (FBP1) have recently been shown to interact and to offer protection against the widespread White Spot Syndrome Virus infection. However, the mechanism is yet unknown. We investigated this interaction in detail by a number of in silico and in vitro analyses, including prediction of a binding site between PmFortilin/FBP1 and docking simulations. The basis of the modeling analyses was well-conserved PmFortilin orthologs, containing a Ca2+-binding domain at residues 76–110 representing a section of the helical domain, the translationally controlled tumor protein signature 1 and 2 (TCTP_1, TCTP_2) at residues 45–55 and 123–145, respectively. We found the pairs Cys59 and Cys76 formed a disulfide bond in the C-terminus of FBP1, which is a common structural feature in many exported proteins and the “x–G–K–K” pattern of the amidation site at the end of the C-terminus. This coincided with our previous work, where we found the “x–P–P–x” patterns of an antiviral peptide also to be located in the C-terminus of FBP1. The combined bioinformatics and in vitro results indicate that FBP1 is a transmembrane protein and FBP1 interact with N-terminal region of PmFortilin