Thiopurine S-methyltransferase genetic polymorphism in the Tunisian population

Background: Determine the incidence of four thiopurine S-methyltransferase (TPMT) mutant alleles, TPMT*2, *3A, *3B and *3C in the Tunisian population involved in adverse drug reactions. Genomic DNAs were isolated from peripheral blood leucocytes of 119 healthy Tunisian volunteers. The frequencies of four allelic variants of the TPMT gene, TPMT*2, *3A, *3B, *3C were determined using allele specific polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism technique.Results: Of the 119 Tunisian subjects participating in this study, 117 subjects (98.3%) were homozygous for TPMT*1 and only two subjects (1.68%) were heterozygous for TPMT*1/*3A. The frequency of TPMT*3A mutant allele was 0.009.Conclusions: Our study provides the first data on the frequency of common TPMT variants in the Tunisian population. TPMT*3A, which causes the largest decrease in enzyme activity, seemed to be a unique variant allele found in this our population.Keywords: Thiopurine S-methyltransferase (TPMT); Pharmacogenetics; Tunisians; PC

Les barotraumatismes de l’oreille moyenne

Objectif : Le barotraumatisme de l’oreille moyenne est une entité pathologique particulière rare et spécifique.Matériel et méthodes : Nous rapportons une série rétrospective de 13 cas de barotraumatismes de l’oreille moyenne diagnostiqués et suivis au centre d’expertise et de médecine aéronautique de Tunis.Résultats : L’âge moyen de nos patients est de 34 ans. Les signes fonctionnels étaient dominés par l’otalgie et l’hypoacousie. L’atteinte était bilatérale dans deux cas. Il s’agissait d’atteinte bénigne de stade (I et II) chez huit patients et d’épanchement rétrotympanique dans quatre cas. Une perforation tympanique a été observée chez un seul pilote. Le bilan clinique a permis de mettre en évidence la présence de circonstances favorisantes à la survenue du barotraumatisme dans neuf cas. Sur le plan fonctionnel, nous avons observés quatre barotraumatismes à audition conservée .Par ailleurs, La surdité était de type transitionnelle. La prise en charge thérapeutique était fonction du bilan lésionnel. L’évolution était favorable chez neufs patients avec une récupération auditive totale.Une dispense de vol fût proclamée dans tous les cas. La durée  d’inaptitude initiale était fonction du bilan lésionnel anatomique et fonctionnel et a variée entre dix et soixante jours.Mots-clés : Barotraumatisme, Surdité, Oreille moyenne, Pilote

Mal de pott révelé par un abcès latéropharyngien chez un pilote

Introduction: Pott's disease is the most frequent localisation of osteoarticular tuberculosis. The authors report a case of cervical Pott's disease with lateropharyngeal abscess.Observation: Our patient is a 44 years old pilot; he presented since 6 months cervicalgy, dysphagia and weighting loss.  Clinical findings showed a swelling of posterior and lateral oropharyngeal wall extending to hypopharynx. A palsy of the XI th nerve and an abolition of the bicipital reflex were also noticed. CT scan showed a lateropharyngeal collection extending from C4 to D1. It was also noticed a subtotal destruction of C6.However, there were no medullar lesions in the cervical spine MRI.Tuberculosis was confirmed thanks to histological analysis of caseum taken during cervical biopy. The patient was operated using anterior approach. He had surgical removal of C6 which was replaced by iliac prothesis. Medical treatment was based on antituberculosis drugs used during 12 months. After three years of follow up, the out come was favourable with no recurrence and satisfying consolidation. For aeronautic considerations, the patient was declared unable for flying mission.Conclusion: Tuberculosis constitutes a problematic infectious disease in Tunisia which may have serious consequences on publish health. We insist on preventing measurements because there are neither specific clinical findings nor radiological characterising features.Keywords: Tuberculosis, Pott's disease, lateropharyngeal absces

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

<p>Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.</p> <p>Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.</p> <p>Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.</p&gt

Bacteriological and physico-chemical assessment of wastewater in different region of Tunisia: impact on human health

<p>Abstract</p> <p>Background</p> <p>In many parts of the world, health problems and diseases have often been caused by discharging untreated or inadequately treated wastewater. In this study, we aimed to control physico-chemical parameters in wastewater samples. Also, microbiological analyses were done to reveal <it>Salmonella </it>strains and each <it>Escherichia coli </it>(<it>E.coli</it>) pathotype.</p> <p>Findings</p> <p>Sixty wastewater samples were collected from fifteen different regions of Tunisia. All physico-chemical parameters (pH, residual free chlorine, total suspended solids, biological oxygen demand, and chemical oxygen demand) were evaluated.</p> <p>For microbiological analyses, samples were filtered to concentrate bacteria. DNA was extracted by boiling and subjected to polymerase chain reaction (PCR) using different pairs of primers.</p> <p>The mean pH values recorded for the sampling point were above the WHO pH tolerance limit. The total suspended solids (TSS) concentrations varied between 240 mg/L and 733 mg/L in entrance points and between 13 mg/L and 76 mg/L in exit points. In entrance points, the studied wastewater has an average COD concentration that varied between 795 mg/mL to 1420 mg/mL. Whereas, BOD concentration of the wastewater ranged between 270 mg/L to 610 mg/L. In exit points, COD concentration varied between 59 mg/L and 141 mg/L, whereas BOD concentration ranged from 15 mg/L to 87 mg/L.</p> <p>The bacteriological control of wastewaters showed that, in entrance points, <it>Escherichia coli </it>(<it>E.coli</it>) was detected at the rate of 76.6%. Three <it>E.coli </it>pathotypes were found: ETEC (53.3%), EAEC (16.6%) and EIEC (6.6%).</p> <p>Concerning the ETEC isolated strains, 8 of 16 (50%) have only the heat-labile toxin gene, 5 of 16 (31.2%) present only the heat-stable toxin gene and 3 of 16 (18.7%) of strains possess both heat-labile toxin gene and heat-stable toxin gene. In exist point, the same pathotypes were found but all detected ETEC strains present only the "est" gene.</p> <p>Concerning <it>Salmonella </it>isolated strains; percentages of 66.6% and 20% were found in entrance and exit points respectively.</p> <p>Conclusions</p> <p>Wastewaters contain a large amount of pathogenic bacteria that present a real impact on human health. Assessment wastewater treatment stations have to consider in account enterobacterial pathogens as potential pathogens that should be correctly controlled.</p

Applying diagnosis and pharmacy-based risk models to predict pharmacy use in Aragon, Spain: The impact of a local calibration

<p>Abstract</p> <p>Background</p> <p>In the financing of a national health system, where pharmaceutical spending is one of the main cost containment targets, predicting pharmacy costs for individuals and populations is essential for budget planning and care management. Although most efforts have focused on risk adjustment applying diagnostic data, the reliability of this information source has been questioned in the primary care setting. We sought to assess the usefulness of incorporating pharmacy data into claims-based predictive models (PMs). Developed primarily for the U.S. health care setting, a secondary objective was to evaluate the benefit of a local calibration in order to adapt the PMs to the Spanish health care system.</p> <p>Methods</p> <p>The population was drawn from patients within the primary care setting of Aragon, Spain (n = 84,152). Diagnostic, medication and prior cost data were used to develop PMs based on the Johns Hopkins ACG methodology. Model performance was assessed through r-squared statistics and predictive ratios. The capacity to identify future high-cost patients was examined through c-statistic, sensitivity and specificity parameters.</p> <p>Results</p> <p>The PMs based on pharmacy data had a higher capacity to predict future pharmacy expenses and to identify potential high-cost patients than the models based on diagnostic data alone and a capacity almost as high as that of the combined diagnosis-pharmacy-based PM. PMs provided considerably better predictions when calibrated to Spanish data.</p> <p>Conclusion</p> <p>Understandably, pharmacy spending is more predictable using pharmacy-based risk markers compared with diagnosis-based risk markers. Pharmacy-based PMs can assist plan administrators and medical directors in planning the health budget and identifying high-cost-risk patients amenable to care management programs.</p

Contribution of copy number variants (CNVs) to congenital, unexplained intellectual and developmental disabilities in Lebanese patients

International audienceBackground: Chromosomal microarray analysis (CMA) is currently the most widely adopted clinical test for patients with unexplained intellectual disability (ID), developmental delay (DD), and congenital anomalies. Its use has revealed the capacity to detect copy number variants (CNVs), as well as regions of homozygosity, that, based on their distribution on chromosomes, indicate uniparental disomy or parental consanguinity that is suggestive of an increased probability of recessive disease. Results: We screened 149 Lebanese probands with ID/DD and 99 healthy controls using the Affymetrix Cyto 2.7 M and SNP6.0 arrays. We report all identified CNVs, which we divided into groups. Pathogenic CNVs were identified in 12.1% of the patients. We review the genotype/phenotype correlation in a patient with a 1q44 microdeletion and refine the minimal critical regions responsible for the 10q26 and 16q monosomy syndromes. Several likely causative CNVs were also detected, including new homozygous microdeletions (9p23p24.1, 10q25.2, and 8p23.1) in 3 patients born to consanguineous parents, involving potential candidate genes. However, the clinical interpretation of several other CNVs remains uncertain, including a microdeletion affecting ATRNL1. This CNV of unknown significance was inherited from the patient's unaffected-mother; therefore, additional ethnically matched controls must be screened to obtain enough evidence for classification of this CNV. Conclusion: This study has provided supporting evidence that whole-genome analysis is a powerful method for uncovering chromosomal imbalances, regardless of consanguinity in the parents of patients and despite the challenge presented by analyzing some CNVs

Nuclear versus mitochondrial DNA: evidence for hybridization in colobine monkeys

<p>Abstract</p> <p>Background</p> <p>Colobine monkeys constitute a diverse group of primates with major radiations in Africa and Asia. However, phylogenetic relationships among genera are under debate, and recent molecular studies with incomplete taxon-sampling revealed discordant gene trees. To solve the evolutionary history of colobine genera and to determine causes for possible gene tree incongruences, we combined presence/absence analysis of mobile elements with autosomal, X chromosomal, Y chromosomal and mitochondrial sequence data from all recognized colobine genera.</p> <p>Results</p> <p>Gene tree topologies and divergence age estimates derived from different markers were similar, but differed in placing <it>Piliocolobus/Procolobus </it>and langur genera among colobines. Although insufficient data, homoplasy and incomplete lineage sorting might all have contributed to the discordance among gene trees, hybridization is favored as the main cause of the observed discordance. We propose that African colobines are paraphyletic, but might later have experienced female introgression from <it>Piliocolobus</it>/<it>Procolobus </it>into <it>Colobus</it>. In the late Miocene, colobines invaded Eurasia and diversified into several lineages. Among Asian colobines, <it>Semnopithecus </it>diverged first, indicating langur paraphyly. However, unidirectional gene flow from <it>Semnopithecus </it>into <it>Trachypithecus </it>via male introgression followed by nuclear swamping might have occurred until the earliest Pleistocene.</p> <p>Conclusions</p> <p>Overall, our study provides the most comprehensive view on colobine evolution to date and emphasizes that analyses of various molecular markers, such as mobile elements and sequence data from multiple loci, are crucial to better understand evolutionary relationships and to trace hybridization events. Our results also suggest that sex-specific dispersal patterns, promoted by a respective social organization of the species involved, can result in different hybridization scenarios.</p