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Background: Urban malaria remains a public health problem. Dakar is located in a low endemic area. However, anti-malarial drugs consumption is reported to be high despite the decline of malaria announced by health authorities. The objective of the present study was to assess the burden of reported malaria attacks (RMAs) in 2008 and to describe care-seeking behaviours in the population of Dakar, Senegal., Methods: In this cross-sectional study, 2,952 households selected from 50 sites were visited. In each household, a women and a child between two and 10 years old were interviewed about a malaria episode that occurred in 2008. The following information was recorded: age, education level, sex (for children), type of care seeking, method of diagnosis, use of anti-malarial treatment, place of medication purchase, bed net use, malaria-related deaths in the family, and perceptions of the frequency of mosquito bites. After a description of the variables in each subsample, a Pearson's chi-square test was used to compare proportions, and logistic regression was performed to identify the association between RMAs and other covariates., Results: Among women, 31.8% reported a malaria attack in 2008; among children, the rate of malaria attacks reported by mothers or caretakers was 39.0%. With regard to care-seeking, 79.5% of women and 81.5% of children with a RMA had visited health facilities (HFs). Younger women and children under five years old were more likely to visit a HF (P<0.001). Presumptive diagnosis was the primary method that was used to identify malaria in HFs. For those who had visited a HF, the rate of anti-malarial treatment was 77% in women and 60% in children. Finally, 43.6% of women and 42.0% of children declared the use of bed nets. In a multivariate analysis, the malaria-related death of a relative and perceptions of mosquito bites were significantly associated with RMAs in women. In children, age was associated with RMAs., Conclusion: The frequent perceptions of the occurrence of malaria in the population were confirmed at the HF by the high presumptive diagnosis of health professionals. Despite the decline of malaria that has been announced by health authorities, the population will continue to complain of malaria and seek care directly at private pharmacies. This situation may sustain the circulation of anti-malarial drugs and increase the risk of an emergence of anti-malarial resistance.

Background: Infant mortality rates (IMR) remain high in many sub-Saharan African countries, especially in rural settings where access to health services may be limited. Studies in such communities can provide relevant data on the burden of and risk factors for infant death. We measured IMR and explored risk factors for infant death in a cohort of children born in Banfora Health District, a rural area in South-West Burkina Faso., Methods: A prospective community-based cohort study was nested within the PROMISE-EBF trial (NCT00397150) in 24 villages of the study area. Maternal and infant baseline characteristics were collected at recruitment and after birth, respectively. Home visits were conducted at weeks 3, 6, 12, 24 and 52 after birth. Descriptive statistics were calculated using robust standard errors to account for cluster sampling. Cox multivariable regression was used to investigate potential risk factors for infant death., Results: Among the 866 live born children included in the study there were 98 infant deaths, yielding an IMR of 113 per 1000 live births (95% CI: 89-143). Over 75% of infant deaths had occurred by 6 months of age and the post neonatal infant mortality rate was 67 per 1000 live births (95% CI: 51-88). Infections (35%) and preterm births complications (23%) were the most common probable causes of death by 6 months. Multivariable analyses identified maternal history of child death, polygyny, twin births and poor anthropometric z-scores at week-3 as factors associated with increased risk of infant death., Conclusions: We observed a very high IMR in a rural area of Burkina Faso, a country where 75% of the population lives in rural settings. Community-based health interventions targeting mothers and children at high risk are urgently needed to reduce the high burden of infant deaths in these areas.

Background: Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low., Methods: One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district., Results: Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to Anopheles gambiae bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and Anopheles mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to Anopheles bites between different exposure groups of districts., Conclusions: Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to Anopheles bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings.

Motivation: The identification of non-coding functional regions of the human genome remains one of the main challenges of genomics. By observing how a given region evolved over time, one can detect signs of negative or positive selection hinting that the region may be functional. With the quickly increasing number of vertebrate genomes to compare with our own, this type of approach is set to become extremely powerful, provided the right analytical tools are available., Results: A large number of approaches have been proposed to measure signs of past selective pressure, usually in the form of reduced mutation rate. Here, we propose a radically different approach to the detection of non-coding functional region: instead of measuring past evolutionary rates, we build a machine learning classifier to predict current substitution rates in human based on the inferred evolutionary events that affected the region during vertebrate evolution. We show that different types of evolutionary events, occurring along different branches of the phylogenetic tree, bring very different amounts of information. We propose a number of simple machine learning classifiers and show that a Support-Vector Machine (SVM) predictor clearly outperforms existing tools at predicting human non-coding functional sites. Comparison to external evidences of selection and regulatory function confirms that these SVM predictions are more accurate than those of other approaches., Availability: The predictor and predictions made are available at http://www.mcb.mcgill.ca/~blanchem/sadri., Contact: blanchem@mcb.mcgill.ca.

Background: There is a scarcity of reliable data on perinatal mortality (PNM) in Sub-Saharan Africa. The PROMISE-EBF trial, during which we promoted exclusive breastfeeding, gave us the opportunity to describe the epidemiology of PNM in Banfora Health District, South-West in Burkina Faso., Study Objectives: To measure the perinatal mortality rate (PNMR) in the PROMISE-EBF cohort in Banfora Health District and to identify potential risk factors for perinatal death., Methods: We used data collected prospectively during the PROMISE-EBF-trial to estimate the stillbirth rate (SBR) and early neonatal mortality rate (ENMR). We used binomial regression with generalized estimating equations to identify potential risk factors for perinatal death., Results: 895 pregnant women were enrolled for data collection in the EBF trial and followed-up to 7 days after birth. The PNMR, the SBR and the ENMR, were 79 per 1000 (95% CI: 59-99), 54 per 1000 (95% CI: 38-69) and 27 per 1000 (95% CI: 9-44), respectively. In a multivariable analysis, nulliparous women (RR = 2.90, 95% CI: 1.6-5.0), primiparae mothers (RR = 2.20, 95% CI: 1.2-3.9), twins (RR = 4.0, 95% CI: 2.3-6.9) and giving birth during the dry season (RR = 2.1 95% CI: 1.3-3.3) were factors associated with increased risk of perinatal death. There was no evidence that risk of perinatal death differed between deliveries at home and at a health centre, Conclusion: Our study observed the highest PNMR ever reported in Burkina. There is an urgent need for sustainable interventions to improve maternal and newborn health in the country.

Summary: The computational inference of ancestral genomes consists of five difficult steps: identifying syntenic regions, inferring ancestral arrangement of syntenic regions, aligning multiple sequences, reconstructing the insertion and deletion history and finally inferring substitutions. Each of these steps have received lot of attention in the past years. However, there currently exists no framework that integrates all of the different steps in an easy workflow. Here, we introduce Ancestors 1.0, a web server allowing one to easily and quickly perform the last three steps of the ancestral genome reconstruction procedure. It implements several alignment algorithms, an indel maximum likelihood solver and a context-dependent maximum likelihood substitution inference algorithm. The results presented by the server include the posterior probabilities for the last two steps of the ancestral genome reconstruction and the expected error rate of each ancestral base prediction., Availability: The Ancestors 1.0 is available at http://ancestors.bioinfo.uqam.ca/ancestorWeb/.

Tumor necrosis factor is a cytokine that plays critical roles in inflammation, the innate immune response, and a variety of other physiologic and pathophysiologic processes. In addition, TNF has recently been shown to mediate an intersection of chronic, low-grade inflammation and concurrent metabolic dysregulation associated with obesity and its comorbidities. As part of an ongoing initiative to further characterize vervet monkeys originating from St Kitts as an animal model of obesity and inflammation, we sequenced and genotyped the human ortholog vervet TNF gene and approximately 1 kb of the flanking 3' and 5' regions from 265 monkeys in a closed, pedigreed colony. This process revealed a total of 11 single-nucleotide polymorphisms (SNPs) and a single 4-bp insertion-deletion, with minor allele frequencies of 0.08 to 0.39. Many of these polymorphisms were in strong or complete linkage disequilibrium with each other, and all but 1 were contained within a single haplotype block, comprising 5 haplotypes with frequencies of 0.075 to 0.298. Using sequences from humans, chimpanzees, vervets, baboons, and rhesus macaques, phylogenetic shadowing of the TNF promoter region revealed that vervet SNPs, like the SNPs in related species, were clustered nonrandomly and nonuniformly around conserved transcription factor binding sites. These data, combined with previously defined heritable phenotypes, permit future association analyses in this nonhuman primate model and have great potential to help dissect the genetic and nongenetic contributions to complex diseases like obesity. More broadly, the sequence data and comparative analyses reported herein facilitates study of the evolution of regulatory sequences of inflammatory and immune-related genes.

Purpose: Diabetes Type I is a chronic disease requiring insulin repeated injections by parenteral during a lifetime. This method of administration as well as traumatic can be a problem for adherence of patients to treatment. In order to overcome these difficulties, we considered the development of therapeutic transdermal drug delivery (TTDD) of insulin., Material and Method: As active ingredient we used anhydrous human insulin Actarapid HM from Novo Nordisk laboratory, the excipients are ethyl cellulose, Eudragit RS 100 and butylphtalate. We developed two matrix Ethylcellulose/Eudragit in reports 1 and 2, in which are incorporated different proportions of insulin., Results: The study of the release of insulin in phosphate buffer at pH 7.4, showed a continuous release profiles strongly depending on Ethylcellulose/Eudragit report and the initial charge of insulin., Conclusion: This study shows that the matrix Ethylcellulose/Eudragit lends itself to the development of a controlled release of insulin. This allows us to continue this work by combining this matrix with other elements for achieving an insulin TTDD.

This chapter introduces the problem of ancestral sequence reconstruction: given a set of extant orthologous DNA genomic sequences (or even whole-genomes), together with a phylogenetic tree relating these sequences, predict the DNA sequence of all ancestral species in the tree. Blanchette et al. (1) have shown that for certain sets of species (in particular, for eutherian mammals), very accurate reconstruction can be obtained. We explain the main steps involved in this process, including multiple sequence alignment, insertion and deletion inference, substitution inference, and gene arrangement inference. We also describe a simulation-based procedure to assess the accuracy of the reconstructed sequences. The whole reconstruction process is illustrated using a set of mammalian sequences from the CFTR region.

In this article we address the problem of phylogenetic inference from nucleic acid data containing missing bases. We introduce a new effective approach, called "Probabilistic estimation of missing values" (PEMV), allowing one to estimate unknown nucleotides prior to computing the evolutionary distances between them. We show that the new method improves the accuracy of phylogenetic inference compared to the existing methods "Ignoring Missing Sites" (IMS), "Proportional Distribution of Missing and Ambiguous Bases" (PDMAB) included in the PAUP software [26]. The proposed strategy for estimating missing nucleotides is based on probabilistic formulae developed in the framework of the Jukes-Cantor [10] and Kimura 2-parameter [11] models. The relative performances of the new method were assessed through simulations carried out with the SeqGen program [20], for data generation, and the Bio NJ method [7], for inferring phylogenies. We also compared the new method to the DNAML program [5] and "Matrix Representation using Parsimony" (MRP) [13], [19] considering an example of 66 eutherian mammals originally analyzed in [17].

A 33-yr-old man undergoing anorectal surgery developed cauda equina syndrome and bilateral profound hearing loss after single-injection spinal anesthesia with isobaric bupivacaine. There was no pain on needle placement. Neurologic assessment found impaired sensation to pinprick in the perineal region, lower extremity paralysis, and bowel and bladder incontinence. In addition, he developed a bilateral profound hearing loss involving the low frequencies, with the left side more affected than the right side. Although hearing impairment can occur with cerebrospinal fluid leakage, the etiology of cauda equina syndrome is uncertain. The simultaneous occurrence of these events has not been previously reported.

The profile of enuretic patients consulting a hospital urology department was reviewed over a period of 15 months based on 102 cases. The study concerned 47 male subjects and 55female subjects with a mean age of 15 +/- 5.3 years. The mean weekly frequency of enuresis was 5.2 +/- 1.9 and enuresis occurred more than once a night for 41.6% of patients. Enuresis was primary in almost 67% of cases. Various aetiological factors for enuresis were identified from analysis of the clinical data and were generally associated: sleep factor (n=93), bladder factor (n=84), hormonalfactor (n=52). Patients were managed as a function of the factors identified. With a mean follow-up of 6 +/- 2.1 months, cure was obtained in 30.4% of cases and improvement was obtained in 24.5%. The various management problems are discussed as a function of socio-economic realities in Senegal and the authors emphasize the need for a multifactorial approach.

Objective: The aim of this study was to report complications of circumcision received in urologic center., Material and Methods: From a retrospective study during a period of 11 years, 63 cases of complications were noticed secondary to traditional circumcision (n = 45) or paramedics (n = 18)., Results: The different complications were: urethral fistulas (n = 41), total or partial glans amputation (n = 9), urethral stricture of the meatus (n = 8), penile pseudo elephantiasis (n = 2), penile denudation (n = 1), hemorragiae (n = 6) and septicaemia (n = 1). The authors underline clinical aspects of these complications and the problems of their treatment.