1,825 research outputs found

    Abnormal Maternal Body Mass Index and Customized Fetal Weight Charts: Improving the Identification of Small for Gestational Age Fetuses and Newborns

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    Maternal body mass index; Newborn weight; ObesityÍndice de masa corporal materno; Peso del neonato; ObesidadÍndex de massa corporal matern; Pes del nounat; ObesitatBackground: Obesity and thinness are serious diseases, but cases with abnormal maternal weight have not been excluded from the calculations in the construction of customized fetal growth curves (CCs). Method: To determine if the new CCs, built excluding mothers with an abnormal weight, are better than standard CCs at identifying SGA. A total of 16,122 neonates were identified as SGA, LGA, or AGA, using the two models. Logistic regression and analysis of covariance were used to calculate the OR and CI for adverse outcomes by group. Gestational age was considered as a covariable. Results: The SGA rates by the new CCs and by the standard CCs were 11.8% and 9.7%, respectively. The SGA rate only by the new CCs was 18% and the SGA rate only by the standard CCs was 0.01%. Compared to AGA by both models, SGA by the new CCs had increased rates of cesarean section, (OR 1.53 (95% CI 1.19, 1.96)), prematurity (OR 2.84 (95% CI 2.09, 3.85)), NICU admission (OR 5.41 (95% CI 3.47, 8.43), and adverse outcomes (OR 1.76 (95% CI 1.06, 2.60). The strength of these associations decreased with gestational age. Conclusion: The use of the new CCs allowed for a more accurate identification of SGA at risk of adverse perinatal outcomes as compared to the standard CCs

    Características clínico-demográficas y tipificación del virus de papiloma humano en mujeres paraguayas con citologías negativas para lesión escamosa intraepitelial

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    Paraguay posee una alta tasa de incidencia de cáncer de cuello uterino de 35/100.0000 mujeres en el año 2008 y el virus de papiloma humano (HPV) es su agente causal. La planificación de medidas de prevención puede ser beneficiada con conocimientos sobre los tipos virales, por ello, el objetivo de este estudio fue determinar características clínico-demográficas y los tipos de HPV presentes en mujeres con citología negativa para lesión escamosa intraepitelial. Estudio de corte transverso con componente analítico en 207 mujeres con citología negativa para lesión escamosa intraepitelial provenientes de centros de salud de Asunción. La tipificación fue realizada por reacción en cadena de la polimerasa utilizando cebadores MY09/11 y GP5/GP6, seguida de polimorfismo de longitud de fragmentos de restricción e hibridación lineal reversa, respectivamente. La asociación entre HPV y las características clínico-demográficas fue determinada por análisis de Chi cuadrado (EpiInfo versión 3,2). Se detectó alta frecuencia de HPV (21%), siendo el tipo predominante HPV 16 (4,3%) seguido de HPV 58/31 (2,4% cada uno). Se observó asociación entre la presencia de HPV y la edad (p=0,0002), detectándose mayor frecuencia de HPV en mujeres menores a 30 años, la cual, disminuyó al aumentar la edad, presentando un ligero aumento en mujeres de 60 años o más. En conclusión, los datos muestran una alta frecuencia de HPV y HPV 16 en mujeres menores a 30 años con citología negativa y sugieren la necesidad de realizar control posteriormente, a fin de identificar las infecciones persistentes que podrían causar lesión de cuello uterino

    Estimating time since infection in early homogeneous HIV-1 samples using a poisson model

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    <p>Abstract</p> <p>Background</p> <p>The occurrence of a genetic bottleneck in HIV sexual or mother-to-infant transmission has been well documented. This results in a majority of new infections being homogeneous, <it>i.e</it>., initiated by a single genetic strain. Early after infection, prior to the onset of the host immune response, the viral population grows exponentially. In this simple setting, an approach for estimating evolutionary and demographic parameters based on comparison of diversity measures is a feasible alternative to the existing Bayesian methods (<it>e.g</it>., BEAST), which are instead based on the simulation of genealogies.</p> <p>Results</p> <p>We have devised a web tool that analyzes genetic diversity in acutely infected HIV-1 patients by comparing it to a model of neutral growth. More specifically, we consider a homogeneous infection (<it>i.e</it>., initiated by a unique genetic strain) prior to the onset of host-induced selection, where we can assume a random accumulation of mutations. Previously, we have shown that such a model successfully describes about 80% of sexual HIV-1 transmissions provided the samples are drawn early enough in the infection. Violation of the model is an indicator of either heterogeneous infections or the initiation of selection.</p> <p>Conclusions</p> <p>When the underlying assumptions of our model (homogeneous infection prior to selection and fast exponential growth) are met, we are under a very particular scenario for which we can use a forward approach (instead of backwards in time as provided by coalescent methods). This allows for more computationally efficient methods to derive the time since the most recent common ancestor. Furthermore, the tool performs statistical tests on the Hamming distance frequency distribution, and outputs summary statistics (mean of the best fitting Poisson distribution, goodness of fit p-value, etc). The tool runs within minutes and can readily accommodate the tens of thousands of sequences generated through new ultradeep pyrosequencing technologies. The tool is available on the LANL website.</p

    Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions

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    <p>Abstract</p> <p>Background</p> <p>The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4<sup>+</sup>, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4<sup>+ </sup>cell count declines to < 350/μL in CD4-guided antiretroviral treatment interruptions.</p> <p>Methods</p> <p>27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4<sup>+ </sup>count > 600/μL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4<sup>+ </sup>cell count to < 350/μL.</p> <p>Results</p> <p>After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4<sup>+ </sup>cell count to < 350/μL. Patients with a CD4<sup>+ </sup>nadir of < 200 cells/μL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to <it>Mycobacterium tuberculosis </it>purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4<sup>+ </sup>cell count to < 350/μL.</p> <p>Conclusion</p> <p>Both the number (CD4<sup>+ </sup>nadir) and the functional activity of CD4<sup>+ </sup>(lymphoproliferative response to PPD) predict the CD4<sup>+ </sup>decrease associated with discontinuation of ART in patients with controlled viremia.</p

    Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension

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    BACKGROUND: There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary evidence indicates that miRNAs regulate the progression of glomerular disease. Indeed, exosomes from the renal system have provided novel evidence in the clinical setting of albuminuria. Thus, the aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension. METHODS: Exosomes were collected from urine specimens from a cohort of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from 20 healthy volunteers as a control group. Urinary exosomes were phenotyped by Western blot, tunable resistive pulse sensing, and electronic microscopy. Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations between albuminuria and exosomal miRNAs were analysed. RESULTS: Urinary miRNAs are highly enriched in exosome subpopulations compared to MVs, both in patients with or without increased albuminuria (p < 0.001), but not in the control group. High albuminuria was associated with 2.5-fold less miR-146a in exosomes (p = 0.017), whereas miR-146a levels in MV did not change. In addition, exosome miR-146a levels were inversely associated with albuminuria (r = 0.65, p < 0.0001), and discriminated the presence of urinary albumin excretion presence [area under the curve = 0.80, 95% confidence interval: 0.66-0.95; p = 0.0013]. CONCLUSIONS: Our results indicate that miRNAs were enriched in the urinary exosome subpopulation in hypertensive patients and that low miR-146a expression in exosomes was associated with the presence of albuminuria. Thus, urinary exosome miR-146a may be a potentially useful tool for studying early renal injury in hypertension

    The striking geographical pattern of gastric cancer mortality in Spain: environmental hypotheses revisited

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    <p>Abstract</p> <p>Background</p> <p>Gastric cancer is decreasing in most countries. While socioeconomic development is the main factor to which this decline has been attributed, enormous differences among countries and within regions are still observed, with the main contributing factors remaining elusive. This study describes the geographic distribution of gastric cancer mortality at a municipal level in Spain, from 1994-2003.</p> <p>Methods</p> <p>Smoothed relative risks of stomach cancer mortality were obtained, using the Besag-York-Molliè autoregressive spatial model. Maps depicting relative risk (RR) estimates and posterior probabilities of RR being greater than 1 were plotted.</p> <p>Results</p> <p>From 1994-2003, 62184 gastric cancer deaths were registered in Spain (7 percent of all deaths due to malignant tumors). The geographic pattern was similar for both sexes. RRs displayed a south-north and coast-inland gradient, with lower risks being observed in Andalusia, the Mediterranean coastline, the Balearic and Canary Islands and the Cantabrian seaboard. The highest risk was concentrated along the west coast of Galicia, broad areas of the Castile & Leon Autonomous community, the province of Cáceres in Extremadura, Lleida and other areas of Catalonia.</p> <p>Conclusion</p> <p>In Spain, risk of gastric cancer mortality displays a striking geographic distribution. With some differences, this persistent and unique pattern is similar across the sexes, suggesting the implication of environmental exposures from sources, such as diet or ground water, which could affect both sexes and delimited geographic areas. Also, the higher sex-ratios found in some areas with high risk of smoking-related cancer mortality in males support the role of tobacco in gastric cancer etiology.</p

    Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro-Inflammatory Responses during Sepsis

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    Background: Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarker among septic patients. Methodology/Principal Findings: Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1 b, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001<=p <= 0.022), and with reduced IL-10 (0.012<= p <=0.047) and elevated CRP (0.011<= p <=0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p =0.017) and ALI (p =0.050) in a combined analysis with European Americans, suggesting common risk effects among studies Conclusions/Significance: These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis

    Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1

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    We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1–5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1–5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV–macaque mucosal infection model for HIV-1 vaccine and microbicide research
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