409 research outputs found

    Sarkopenija – skrandžio vėžio chirurgijoje neįvertintas rizikos veiksnys

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    Surgery remains the only potentially curative option for gastric cancer, although it is related to high postoperative morbidity and mortality rate. Approximately every second gastric cancer patient is diagnosed with sarcopenia, which is a significant risk factor for postoperative complications and poor long-term outcomes. However, sarcopenia is underestimated in routine clinical practice, since it remains the interest of clinical trials. Sarcopenia diagnostic criteria are not fully standardized, but it consists of tests for muscle strength, quantity and quality. They include grip strength, chair stand test, computed tomography, magnetic resonance imaging, ultrasound, bioelectrical impedance analysis and densitometry tests. Regarding the growing evidence for sarcopenia impact on surgical gastric cancer treatment results, it is a high probability that sarcopenia assessment will come to routine clinical practice. Although, until then there is a need for further clinical trials to standardize the diagnostic and to find effective treatment strategies.Chirurgija yra pagrindinis skrandžio vėžio gydymo metodas, leidžiantis tikėtis visiško pasveikimo. Operacijos dėl skrandžio vėžio yra didelės apimties, jos susijusios su didele pooperacinių komplikacijų rizika. Maždaug pusei sergančiųjų skrandžio vėžiu nustatoma sarkopenija. Tai reikšmingas pooperacinių komplikacijų rizikos veiksnys, lemiantis prastesnius atokiuosius gydymo rezultatus.Sarkopenija vis dar yra tik klinikinių tyrimų objektas, šiandienos rutininėje klinikinėje praktikoje ji nevertinama. Sarkopenijos diagnostika apima tyrimus, kuriais siekiama nustatyti raumenų jėgą, masę ir kokybę, tačiau diagnostikos metodika nėra galutinai standartizuota. Diag­nostikai taikomi plaštakos griebimo jėgos, „sėsti – stoti“ testo, kompiuterinės tomografijos, magnetinio rezonanso, ultragarso, bioimpedanso ir densitometrijos tyrimai.Sarkopenijos reikšmė skrandžio vėžiui gydyti vis labiau auga. Tikėtina, kad netolimoje ateityje sarkopenijos vertinimas ir gydymas taps kasdienės klinikinės praktikos dalimi. Taigi tikslinga atlikti papildomus klinikinius tyrimus, kurie padėtų standartizuoti diagnostiką ir rasti efektyvius gydymo metodus

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

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    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

    Change in Composition of the Anopheles Gambiae Complex and its Possible Implications for the Transmission of Malaria and Lymphatic Filariasis in North-Eastern Tanzania.

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    A dramatic decline in the incidence of malaria due to Plasmodium falciparum infection in coastal East Africa has recently been reported to be paralleled (or even preceded) by an equally dramatic decline in malaria vector density, despite absence of organized vector control. As part of investigations into possible causes for the change in vector population density, the present study analysed the Anopheles gambiae s.l. sibling species composition in north-eastern Tanzania. The study was in two parts. The first compared current species complex composition in freshly caught An. gambiae s.l. complex from three villages to the composition reported from previous studies carried out 2-4 decades ago in the same villages. The second took advantage of a sample of archived dried An. gambiae s.l. complex specimens collected regularly from a fourth study village since 2005. Both fresh and archived dried specimens were identified to sibling species of the An. gambiae s.l. complex by PCR. The same specimens were moreover examined for Plasmodium falciparum and Wuchereria bancrofti infection by PCR. As in earlier studies, An. gambiae s.s., Anopheles merus and Anopheles arabiensis were identified as sibling species found in the area. However, both study parts indicated a marked change in sibling species composition over time. From being by far the most abundant in the past An. gambiae s.s. was now the most rare, whereas An. arabiensis had changed from being the most rare to the most common. P. falciparum infection was rarely detected in the examined specimens (and only in An. arabiensis) whereas W. bancrofti infection was prevalent and detected in all three sibling species. The study indicates that a major shift in An. gambiae s.l. sibling species composition has taken place in the study area in recent years. Combined with the earlier reported decline in overall malaria vector density, the study suggests that this decline has been most marked for An. gambiae s.s., and least for An. arabiensis, leading to current predominance of the latter. Due to differences in biology and vectorial capacity of the An. gambiae s.l. complex the change in sibling species composition will have important implications for the epidemiology and control of malaria and lymphatic filariasis in the study area

    Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

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    The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

    The nonadaptive nature of the H1N1 2009 Swine Flu pandemic contrasts with the adaptive facilitation of transmission to a new host

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    <p>Abstract</p> <p>Background</p> <p>The emergence of the 2009 H1N1 Influenza pandemic followed a multiple reassortment event from viruses originally circulating in swines and humans, but the adaptive nature of this emergence is poorly understood.</p> <p>Results</p> <p>Here we base our analysis on 1180 complete genomes of H1N1 viruses sampled in North America between 2000 and 2010 in swine and human hosts. We show that while transmission to a human host might require an adaptive phase in the HA and NA antigens, the emergence of the 2009 pandemic was essentially nonadaptive. A more detailed analysis of the NA protein shows that the 2009 pandemic sequence is characterized by novel epitopes and by a particular substitution in loop 150, which is responsible for a nonadaptive structural change tightly associated with the emergence of the pandemic.</p> <p>Conclusions</p> <p>Because this substitution was not present in the 1918 H1N1 pandemic virus, we posit that the emergence of pandemics is due to epistatic interactions between sites distributed over different segments. Altogether, our results are consistent with population dynamics models that highlight the epistatic and nonadaptive rise of novel epitopes in viral populations, followed by their demise when the resulting virus is too virulent.</p

    Spatio-temporal Models of Lymphangiogenesis in Wound Healing

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    Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

    Influenza vaccine uptake among community-dwelling Italian elderly: results from a large cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Flu vaccination significantly reduces the risk of serious complications like hospitalization and death among community-dwelling older people, therefore vaccination programmes targeting this population group represent a common policy in developed Countries. Among the determinants of vaccine uptake in older age, a growing literature suggests that social relations can play a major role.</p> <p>Methods</p> <p>Drawing on the socio-behavioral model of Andersen-Newman - which distinguishes predictors of health care use in predisposing characteristics, enabling resources and need factors - we analyzed through multilevel regressions the determinants of influenza immunization in a sample of 25,183 elderly reached by a nationally representative Italian survey.</p> <p>Results</p> <p>Being over 85-year old (OR = 1.99; 95% CI 1.77 - 2.21) and suffering from a severe chronic disease (OR = 2.06; 95% CI 1.90 - 2.24) are the strongest determinants of vaccine uptake. Being unmarried (OR = 0.81; 95% CI 0.74 - 0.87) and living in larger households (OR = 0.83; 95% CI 0.74 - 0.87) are risk factors for lower immunization rates. Conversely, relying on neighbors' support (OR = 1.09; 95% CI 1.02 - 1.16) or on privately paid home help (OR = 1.19; 95% CI 1.08 - 1.30) is associated with a higher likelihood of vaccine uptake.</p> <p>Conclusions</p> <p>Even after adjusting for socio-demographic characteristics and need factors, social support, measured as the availability of assistance from partners, neighbors and home helpers, significantly increases the odds of influenza vaccine use among older Italians.</p

    Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

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    BackgroundCigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.Methods and findingsA total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (ConclusionsThe probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause

    Determination of EGFR Endocytosis Kinetic by Auto-Regulatory Association of PLD1 with mu 2

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    Background: Upon ligand binding, cell surface signaling receptors are internalized through a process tightly regulated by endocytic proteins and adaptor protein 2 (AP2) to orchestrate them. Although the molecular identities and roles of endocytic proteins are becoming clearer, it is still unclear what determines the receptor endocytosis kinetics which is mainly regulated by the accumulation of endocytic apparatus to the activated receptors. Methodology/Principal Findings: Here we employed the kinetic analysis of endocytosis and adaptor recruitment to show that ??2, a subunit of AP2 interacts directly with phospholipase D (PLD)1, a receptor-associated signaling protein and this facilitates the membrane recruitment of AP2 and the endocytosis of epidermal growth factor receptor (EGFR). We also demonstrate that the PLD1-??2 interaction requires the binding of PLD1 with phosphatidic acid, its own product. Conclusions/Significance: These results suggest that the temporal regulation of EGFR endocytosis is achieved by auto-regulatory PLD1 which senses the receptor activation and triggers the translocation of AP2 near to the activated receptor.open3

    The InterLACE study: Design, Data Harmonization and Characteristics Across 20 Studies on Women’s Health

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    Objectives: The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women’s reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE. Study design: InterLACE is an individual-level pooled study of 20 observational studies (12 of which are longitudinal) from ten countries. Variables were harmonized across studies to create a new and systematic synthesis of life-course data. Main outcome measures: Harmonized data were derived in three domains: 1) socio-demographic and lifestyle factors, 2) female reproductive characteristics, and 3) chronic disease outcomes (cardiovascular disease (CVD) and diabetes). Results: InterLACE pooled data from 229,054 mid-aged women. Overall, 76% of the women were Caucasian and 22% Japanese; other ethnicities (of 300 or more participants) included Hispanic/Latin American (0.2%), Chinese (0.2%), Middle Eastern (0.3%), African/black (0.5%), and Other (1.0%). The median age at baseline was 47 years (Inter-quartile range (IQR): 41–53), and that at the last follow-up was 56 years (IQR: 48–64). Regarding reproductive characteristics, half of the women (49.8%) had their first menstruation (menarche) at 12–13 years of age. The distribution of menopausal status and the prevalence of chronic disease varied considerably among studies. At baseline, most women (57%) were pre- or peri-menopausal, 20% reported a natural menopause (range 0.8–55.6%) and the remainder had surgery or were taking hormones. By the end of follow-up, the prevalence rates of CVD and diabetes were 7.2% (range 0.9–24.6%) and 5.1% (range 1.3–13.2%), respectively. Conclusions: The scale and heterogeneity of InterLACE data provide an opportunity to strengthen evidence concerning the relationships between reproductive health through life and subsequent risks of chronic disease, including cross-cultural comparisons
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