Epidemiological analysis of peripartum hysterectomy across nine European countries

Introduction Peripartum hysterectomy is a surgical procedure performed for severe obstetric complications such as major obstetric hemorrhage. The prevalence of peripartum hysterectomy in high-resource settings is relatively low. Hence, international comparisons and studying indications and associations with mode of birth rely on the use of national obstetric survey data. Objectives were to calculate the prevalence and indications of peripartum hysterectomy and its association with national cesarean section rates and mode of birth in nine European countries. Material and methods We performed a descriptive, multinational, population-based study among women who underwent peripartum hysterectomy. Data were collected from national or multiregional databases from nine countries participating in the International Network of Obstetric Survey Systems. We included hysterectomies performed from 22 gestational weeks up to 48 hours postpartum for obstetric hemorrhage, as this was the most restrictive, overlapping case definition between all countries. Main outcomes were prevalence and indications of peripartum hysterectomy. Additionally, we compared prevalence of peripartum hysterectomy between women giving birth vaginally and by cesarean section, and between women giving birth with and without previous cesarean section. Finally, we calculated correlation between prevalence of peripartum hysterectomy and national cesarean section rates, as well as national rates of women giving birth after a previous cesarean section. Results A total of 1302 peripartum hysterectomies were performed in 2 498 013 births, leading to a prevalence of 5.2 per 10 000 births ranging from 2.6 in Denmark to 10.7 in Italy. Main indications were uterine atony (35.3%) and abnormally invasive placenta (34.8%). Relative risk of hysterectomy after cesarean section compared with vaginal birth was 9.1 (95% CI 8.0-10.4). Relative risk for hysterectomy for birth after previous cesarean section compared with birth without previous cesarean section was 10.6 (95% CI 9.4-12.1). A strong correlation was observed between national cesarean section rate and prevalence of peripartum hysterectomy (rho = 0.67, P < .05). Conclusions Prevalence of peripartum hysterectomy may vary considerably between high-income countries. Uterine atony and abnormally invasive placenta are the commonest indications for hysterectomy. Birth by cesarean section and birth after previous cesarean section are associated with nine-fold increased risk of peripartum hysterectomy

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Quantification of the efficiency of treatment of Anopheles gambiae breeding sites with petroleum products by local communities in areas of insecticide resistance in the Republic of Benin

<p>Abstract</p> <p>Background</p> <p>The emergence of <it>Anopheles </it>populations capable of withstanding lethal doses of insecticides has weakened the efficacy of most insecticide based strategies of vector control and, has highlighted the need for developing new insecticidal molecules or, improving the efficacy of existing insecticides or abandoning those to which resistance has emerged. The use of petroleum products (PP) against mosquito larvae had an immense success during early programmes of malaria control, but these compounds were abandoned and replaced in the 1950s by synthetic insecticides probably because of the high performances given by these new products. In the current context of vector resistance, it is important to elucidate the empirical use of PP by quantifying their efficiencies on resistant strains of <it>Anopheles</it>.</p> <p>Methods</p> <p>Larvae of <it>Anopheles </it>Ladji a local resistant strain were exposed to increasing concentrations of various PP (kerosene, petrol and engine oils) for 24 hours and the lethal activities recorded. The highest concentration (HiC) having no lethal activity (also referred as the NOEL or no effect level) and the lowest concentration (LoC₁₀₀) yielding 100% mortality were rated for each PP on the Ladji strain. Prior to laboratory analysis, KAP studies were conducted in three traditional communities were insecticide resistance is clearly established to confirm the use of PP against mosquitoes.</p> <p>Results</p> <p>Laboratory analysis of petrol, kerosene and engine oils, clearly established their lethal activities on resistant strains of <it>Anopheles </it>larvae. Contrary to existing references, this research revealed that exposed larvae of <it>Anopheles </it>were mostly killed by direct contact toxicity and not by suffocation as indicated in some earlier reports.</p> <p>Conclusion</p> <p>This research could serve as scientific basis to backup the empirical utilisation of PP on mosquito larvae and to envisage possibilities of using PP in some traditional settings where <it>Anopheles </it>have developed resistance to currently used insecticides.</p

A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target

The identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning (“Causal Reasoning Analytical Framework for Target discovery”—CRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy

The prognostic value of four interleukin-1 gene polymorphisms in caucasian women with breast cancer – a multicenter study

<p>Abstract</p> <p>Background</p> <p>The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown.</p> <p>Methods</p> <p>We studied the influence of four common gene polymorphisms (<it>IL1A </it>-889C/T, <it>IL1B </it>-511C/T, <it>IL1B </it>+3953E1/E2, and <it>IL1RN </it>long/2) of the IL-1 family on survival in 262 Caucasian patients with breast cancer by univariate and multivariate survival analysis. The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis.</p> <p>Results</p> <p>In the present study 38 cases of cancer related death and a median time of follow-up (range) of 55.3 (0.4–175.8) months was observed. <it>IL1RN </it>2/2 (homozygous mutant) gene polymorphism was associated with shortened disease free and overall survival in a univariate (p = 0.001 and p = 0.01, respectively) and multivariate analysis (p = 0.002, Odds Ratio [95% Confidence Interval] = 3.6 [1.6–8.0] and p = 0.05, Odds Ratio = 3.0 [1.1–9.3], respectively). Presence of the homozygous mutant genotype of the <it>IL1A </it>-889 and <it>IL1B </it>+3953 gene polymorphism was associated with overall survival in the univariate (p = 0.004 and p = 0.002, respectively), but not in the multivariate analysis. No association was observed between all possible haplotype combinations and overall survival.</p> <p>Conclusion</p> <p>Carriage of the mutant alleles of <it>IL1RN </it>was independently associated with shortened disease free and overall survival rates in Caucasian patients with breast cancer.</p

Cerebrospinal fluid biomarker candidates associated with human WNV neuroinvasive disease

During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presente

Development of vegetable farming: a cause of the emergence of insecticide resistance in populations of Anopheles gambiae in urban areas of Benin

<p>Abstract</p> <p>Background</p> <p>A fast development of urban agriculture has recently taken place in many areas in the Republic of Benin. This study aims to assess the rapid expansion of urban agriculture especially, its contribution to the emergence of insecticide resistance in populations of <it>Anopheles gambiae</it>.</p> <p>Methods</p> <p>The protocol was based on the collection of sociological data by interviewing vegetable farmers regarding various agricultural practices and the types of pesticides used. Bioassay tests were performed to assess the susceptibility of malaria vectors to various agricultural insecticides and biochemical analysis were done to characterize molecular status of population of <it>An. gambiae</it>.</p> <p>Results</p> <p>This research showed that:</p> <p>(1) The rapid development of urban agriculture is related to unemployment observed in cities, rural exodus and the search for a balanced diet by urban populations;</p> <p>(2) Urban agriculture increases the farmers' household income and their living standard;</p> <p>(3) At a molecular level, PCR revealed the presence of three sub-species of <it>An. gambiae </it>(<it>An. gambiae s.s., Anopheles melas and Anopheles arabiensis</it>) and two molecular forms (M and S). The <it>kdr </it>west mutation recorded in samples from the three sites and more specifically on the M forms seems to be one of the major resistance mechanisms found in <it>An. gambiae </it>from agricultural areas. Insecticide susceptibility tests conducted during this research revealed a clear pattern of resistance to permethrin (76% mortality rate at Parakou; 23.5% at Porto-Novo and 17% at Cotonou).</p> <p>Conclusion</p> <p>This study confirmed an increase activity of the vegetable farming in urban areas of Benin. This has led to the use of insecticide in an improper manner to control vegetable pests, thus exerting a huge selection pressure on mosquito larval population, which resulted to the emergence of insecticide resistance in malaria vectors.</p