Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

Absence of influenza vaccination among high-risk older adults in Taiwan

<p>Abstract</p> <p>Background</p> <p>Older adults, who often have more than one chronic disease, are at greater risk of influenza and its complications. However, because they often see physicians for other more pressing complaints, their physicians, focusing on one condition, may forget to suggest preventive measures for other diseases such as influenza. This study investigates what major factors affect an older adult with more than one chronic condition missing a vaccination opportunity.</p> <p>Methods</p> <p>Retrospectively reviewing a nationally representative random sample of medical claims from Taiwan's National Health Insurance Research Database during the period 2004 - 2006, we first identified patients sixty-five years or older who had visited physicians. Each patient was assigned a proxy for health status, the Charlson Comorbidity Index (CCI) score. An older claimant was defined has having "absence of a vaccination" when he or she had visited a physician during an influenza season but did not receive an influenza vaccination. Multivariate logistic regression was performed to estimate how likely it would be for older adults with various CCI scores to miss a vaccination.</p> <p>Results</p> <p>Out of 200,000 randomly selected claims, 20,923 older adults were included in our final analysis. We found older adults with higher CCIs to be more likely to have an absence of vaccination (<it>p </it>< 0.01). Our multivariate logistic regression results revealed CCI to be the greatest predictor of absence of vaccination, after controlling for individual factors and medical setting. Older adults with CCI scores three or higher were nearly five times more likely to miss a vaccination than those with a CCI of zero [OR: 4.93 (95%CI, 4.47-5.42)]. Those with CCIs of one and two were 2.53 and 3.92 times more likely to miss vaccination than those with a CCI of zero [OR 2.53 (95%CI, 2.26-2.84) and OR 3.92 (95%CI, 3.51-4.38), respectively].</p> <p>Conclusions</p> <p>The greater the number of certain comorbid conditions, the greater the likelihood a flu vaccination will be missed. Physicians would be well advised to not let the presenting problems of older patients distract from other possible health problems that might also need attention, in this case influenza vaccinations.</p

An Alternate Method of Classifying Allergic Bronchopulmonary Aspergillosis Based on High-Attenuation Mucus

Allergic bronchopulmonary aspergillosis (ABPA) is classified radiologically based on the findings of central bronchiectasis (CB) and other radiologic features (ORF). However, the long-term clinical significance of these classifications remains unknown. We hypothesized that the immunological activity and outcomes of ABPA could be predicted on HRCT chest finding of high-attenuation mucus (HAM), a marker of inflammatory activity. In this study, we evaluate the severity and clinical outcomes of ABPA with different radiological classifications. specific IgE levels, eosinophil count) severity of the disease and clinical outcomes in various classifications were analyzed.Of the 234 (123 males, 111 females; mean age, 34.1 years) patients, 55 (23.5%) had normal HRCT, 179 (76.5%) had CB, 49 (20.9%) had HAM, and 27 (11.5%) had ORF. All immunological markers were consistently higher in the HAM classification, while in other classifications these findings were inconsistent. On multivariate analysis, the factors predicting frequent relapses were presence of HAM (OR 7.38; 95% CI, 3.21–17.0) and CB (OR 3.93; 95% CI, 1.63–9.48) after adjusting for ORF.The classification scheme based on HAM most consistently predicts immunological severity in ABPA. Central bronchiectasis and HAM are independent predictors of recurrent relapses in ABPA. Hence, HAM should be employed in the radiological classification of ABPA

Radiographic joint space narrowing in osteoarthritis of the knee: relationship to meniscal tears and duration of pain

[[abstract]]Objective The objective of this study was to assess, with knee radiography, joint space narrowing (JSN) and its relationship to meniscal tears, anterior cruciate ligament (ACL) ruptures, articular cartilage erosion, and duration of pain in patients with knee osteoarthritis. Materials and methods A total of 140 patients who had knee osteoarthritis and underwent primary total knee replacement (TKR) surgery, with unicompartmental medial tibiofemoral JSN (grade 1 or greater) and normal lateral compartments, were recruited. Polytomous logistic regression was used to assess the relationship between JSN and risk factors. Results All patients with JSN were categorized as grade 1 (n = 14, 10.0%), grade 2 (n = 64, 45.7%), or grade 3 (n = 62, 44.3%). Women presented with indications for a TKR at a younger age than men (mean age, 69 vs 73 years, P < 0.05). There were 123 (87.9%) meniscal tears and 58 (41.4%) partial (insufficient or attenuated ACL fibers) and 10 (7.1%) complete ACL ruptures; 115 of 134 (85.8%) patients had moderate to severe cartilage erosion. A higher grade of JSN was correlated with a higher frequency of meniscal tears [odds ratio (OR) 6.00, 95% CI 1.29–27.96 for grade 2 vs grade 1 JSN] and duration of knee pain (OR 1.25, 95% CI 1.01–1.53 for grade 3 vs grade 1 JSN). A higher grade of JSN was not correlated with a higher frequency of ACL rupture or articular cartilage erosion. Conclusion A higher grade of JSN is associated with a higher frequency of meniscal tears and long duration of knee pain in patients with knee osteoarthritis.[[incitationindex]]SCI[[booktype]]紙

Habitat-Mediated Facilitation and Counteracting Ecosystem Engineering Interactively Influence Ecosystem Responses to Disturbance

Recovery of an ecosystem following disturbance can be severely hampered or even shift altogether when a point disturbance exceeds a certain spatial threshold. Such scale-dependent dynamics may be caused by preemptive competition, but may also result from diminished self-facilitation due to weakened ecosystem engineering. Moreover, disturbance can facilitate colonization by engineering species that alter abiotic conditions in ways that exacerbate stress on the original species. Consequently, establishment of such counteracting engineers might reduce the spatial threshold for the disturbance, by effectively slowing recovery and increasing the risk for ecosystem shifts to alternative states. We tested these predictions in an intertidal mudflat characterized by a two-state mosaic of hummocks (humps exposed during low tide) dominated by the sediment-stabilizing seagrass Zostera noltii) and hollows (low-tide waterlogged depressions dominated by the bioturbating lugworm Arenicola marina). In contrast to expectations, seagrass recolonized both natural and experimental clearings via lateral expansion and seemed unaffected by both clearing size and lugworm addition. Near the end of the growth season, however, an additional disturbance (most likely waterfowl grazing and/or strong hydrodynamics) selectively impacted recolonizing seagrass in the largest (1 m2) clearings (regardless of lugworm addition), and in those medium (0.25 m2) clearings where lugworms had been added nearly five months earlier. Further analyses showed that the risk for the disturbance increased with hollow size, with a threshold of 0.24 m2. Hollows of that size were caused by seagrass removal alone in the largest clearings, and by a weaker seagrass removal effect exacerbated by lugworm bioturbation in the medium clearings. Consequently, a sufficiently large disturbance increased the vulnerability of recolonizing seagrass to additional disturbance by weakening seagrass engineering effects (sediment stabilization). Meanwhile, the counteracting ecosystem engineering (lugworm bioturbation) reduced that threshold size. Therefore, scale-dependent interactions between habitat-mediated facilitation, competition and disturbance seem to maintain the spatial two-state mosaic in this ecosystem

Number of siblings and the risk of solid tumours: a nation-wide study

We analysed the effects of number of siblings on the risk of solid tumours using the Swedish Family-Cancer Database, including population-based information on over 11 million individuals and more than 178 000 cancer patients diagnosed between 1958 and 2004. Incidence rate ratios (RRs), estimated by Poisson regression models, were adjusted for age, sex, birth cohort, area of residence and socioeconomic status. Having eight or more siblings vs none increased the risk of stomach cancer (RR=1.83, 95% confidence interval (CI), 1.44–2.34). Anal cancer diagnosed before age 40 showed the strongest association with the total siblings (RR=3.27, 95% CI, 2.04–5.26 for five or more siblings vs none). Endometrial (RR=0.76, 95% CI, 0.70–0.82), testicular (RR=0.71, 95% CI, 0.62–0.82), skin cancer (RR=0.82, 95% CI, 0.69–0.97) and melanoma (RR=0.72, 95% CI, 0.65–0.79) showed strong decreased risks for five or more siblings vs none. Prostate cancer risk for those with five or more older siblings vs none was 1.38 (95% CI, 1.23–1.55). Having five or more younger siblings was most strongly associated with stomach cancer (RR=1.59, 95% CI, 1.29–1.95) and melanoma (RR=0.68, 95% CI, 0.59–0.79). We conclude that sibship characteristics are strong correlates of cancer risk at several sites; plausible interpretations include socioeconomic status

Mutations in Wnt2 Alter Presynaptic Motor Neuron Morphology and Presynaptic Protein Localization at the Drosophila Neuromuscular Junction

Wnt proteins are secreted proteins involved in a number of developmental processes including neural development and synaptogenesis. We sought to determine the role of the Drosophila Wnt7b ortholog, Wnt2, using the neuromuscular junction (NMJ). Mutations in wnt2 produce an increase in the number of presynaptic branches and a reduction in immunolabeling of the active zone proteins, Bruchpilot and synaptobrevin, at the NMJ. There was no change, however, in immunolabeling for the presynaptic proteins cysteine-string protein (CSP) and synaptotagmin, nor the postsynaptic proteins GluRIIA and DLG at the NMJ. Consistent with the presynaptic defects, wnt2 mutants exhibit approximately a 50% reduction in evoked excitatory junctional currents. Rescue, RNAi, and tissue-specific qRT-PCR experiments indicate that Wnt2 is expressed by the postsynaptic cell where it may serve as a retrograde signal that regulates presynaptic morphology and the localization of presynaptic proteins

Evolutionary Trends of A(H1N1) Influenza Virus Hemagglutinin Since 1918

The Pandemic (H1N1) 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA) is the major agent for host-driven antigenic drift in A(H3N2) virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1). Here, by analyzing hundreds of A(H1N1) HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1) HAs. Among a subgroup of human A(H1N1) HAs between 1918∼2008, we found strong diversifying (positive) selection at HA1 156 and 190. We also analyzed the evolutionary trends at HA1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1) HA. Different A(H1N1) viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1) HAs favor HA1 190 while the 1918 pandemic and swine HAs favor HA1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1) influenza viruses