Congenital factor XIII deficiency caused by two mutations in eight Tunisian families: molecular confirmation of a founder effect

Inherited factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by an umbilical bleeding during the neonatal period, delayed soft tissue bruising, mucosal bleeding spontaneous intracranial hemorrhage, and soft tissue hemorrhages. Congenital FXIII deficiency is an autosomal recessive disorder, usually attributed to a defect in the FXIIIA and B subunits coding, respectively, by F13A and F13B genes. The aim of this study was to determine the molecular defects responsible for congenital factor XIII deficiency in eight Tunisian families. Molecular analysis was performed by direct DNA sequencing of polymerase chain reaction amplified fragments spanning the coding regions and splice junctions of the FXIIIA subunit gene (F13A) in probands and in families' members and compared with the reported sequence of this gene. In all patients, FXIIIA activity was undetectable and the FXIIIB was within the normal range. Direct sequencing of the F13A gene in all probands showed two mutations: the c.869insC mutation found in eight patients and the c.1226G?>?A transition found in only one. We also confirmed the presence of a founder effect for the first frequent mutation by using two microsatellite markers, HUMF13A01 and a generated ployAC marker (HUMF13A02). We describe here molecular abnormalities found in nine Tunisian probands diagnosed with FXIIIA deficiency. The identification of the founder mutation and polymorphisms allowed a genetic counseling in relatives of these families, and the antenatal diagnosis is now available.     

Glyphosate and glyphosate‐based herbicide exposure during the peripartum period affects maternal brain plasticity,maternal behaviour and microbiome

Glyphosate is found in a large array of non‐selective herbicides such as Roundup® (Monsanto, Creve Coeur, MO, USA) and is by far the most widely used herbicide. Recent work in rodent models suggests that glyphosate‐based herbicides during development can affect neuronal communication and result in altered behaviours, albeit through undefined mechanisms of action. To our knowledge, no study has investigated the effects glyphosate or its formulation in herbicide on maternal behaviour and physiology. In the present study, relatively low doses of glyphosate (5 mg kg^‐1 d^‐1), Roundup® (5 mg kg^‐1 d^‐1 glyphosate equivalent), or vehicle were administered by ingestion to Sprague‐Dawley rats from gestational day (GD) 10 to postpartum day (PD)22. The treatments significantly altered licking behaviour toward pups between PD2 and PD6. We also show in the dams at PD22 that Roundup exposure affected the maturation of doublecortin‐immunoreactive new neurones in the dorsal dentate gyrus of the hippocampus of the mother. In addition, the expression of synaptophysin was up‐regulated by glyphosate in the dorsal and ventral dentate gyrus and CA3 regions of the hippocampus, and down‐regulated in the cingulate gyrus. Although a direct effect of glyphosate alone or its formulation on the central nervous system is currently not clear, we show that gut microbiota is significantly altered by the exposure to the pesticides, with significant alteration of the phyla Bacteroidetes and Firmicutes. This is the first study to provide evidence that glyphosate alone or in formulation (Roundup) differentially affects maternal behaviour and modulates neuroplasticity and gut microbiota in the mother.     

Design parameters optimization of a particles impact damper

Particles impact damping is one of the promising technologies used for the passive mitigation of vibrations. Through the dynamic impact and friction between particles, particles impact damper is able to reduce or eliminate vibratory energy under kinetic shape. Due to the simplicity of this type of damper and the operating frequency band, it is widely used in civil engineering. On the other hand it can operate in aggressive environments including high temperature or humidity. In this paper, the dynamic behaviour and efficiency of this process to reduce vibrations are highlighted. Using a simple analytical model, a clamped-free beam coupled to a particles impact damper, the influence of some system parameters is investigated. The proposed model is, then, validated through a comparison of simulated responses with experimental results established in a previous work. It is noticed that the nonlinear behaviour and the large number of their design parameters make the determination of its participation in damp very complicated. For this reason, it is crucial to seek optimal design parameters of the particles impact damper. In this context, an optimized method based on a genetic algorithm is proposed. The obtained results demonstrate the satisfactory side of this approach to identify the optimal parameters of the considered particles impact damper. Consequently, the developed approach may be constitutes an aid, for the engineer, to choose particles impact damper parameters according to the characteristics of the vibrating structure to be studied.     

Successful pregnancies after transvenous cardiac resynchronization therapy in a woman with congenitally corrected transposition of the great arteries

Congenitally corrected transposition of the great arteries is a rare heart defect that can be associated with systemic ventricular dysfunction and conduction disturbances. The use of cardiac resynchronization therapy in patients with congenital heart disease is not fully established, and achievement of successful pregnancies after implantation of transvenous, biventricular system has never been described, and which resulted in a significant clinical improvement.We describe a 33-year-old female with congenitally corrected transposition of the great arteries, who achieved six pregnancies and successful vaginal deliveries. The two last pregnancies were achieved after cardiac resynchronization therapy for systemic ventricular dysfunction and complete heart block. A congenital cardiac disease has been identified in only one offspring.     

Central agenesis of the hand

Central aplasia represent under 10% of congenital malformations of the hand. It is characterised by the partial or complete absence of the median ray. We adopted the classification of Swanson and considered this anomaly a stop of median longitudinal development. We separate 2 groups: Hand in folk: the aplasia interested only the median digits, all metacarpal are present. Hand in lobster's pincer: all median rays are absent including the metacarpal. We report a set of 16 children carriers of 23 central aplasia of the hand, it was about 14 hands in lobster'pincer and 9 hands in folk. In any case, the gene was merely aesthetic, the hand's function was complete. A child has been operated, and benefitted a closing of the median crack defect, he had a free thumb. For the other cases, abstention has been decided, indeed to close this cracks deprive these hands of a first corner the alone present.     

Prognostic impact of karyotype in de novo acute myeloid leukemia: study of 139 cases

A group of 139 patients with de novo acute myeloid leukemia were investigated to determine the prognostic significance of karyotype on early death, complete remission, continuous complete remission and survival. There were 27 children and 112 adults. Mean age was 32 years. t(15;17) was found associated with a high rate of early death and a diploid karyotype with long continuous complete remission. The presence of a structural change was predictive of shorter survivals. The study of the prognostic impact of recurrent anomalies reveals a good prognostic impact for normal karyotype (1 year survival probability: 40%), followed by t(8;21) (1 year survival probability: 24%), and by t(15;17) (1 year survival probability: 9%).     

Struma ovarii. Analysis of a series of 7 cases and review of the literature

The authors report the result of a retrospective study of 7 cases of struma ovarii, four malignant and three benign cases, removed surgically at the Salah Azaiez Institute, Tunis, Tunisia, over a period of 20 years (1980-2000). Based on their personal experience and on a review of the literature, the authors discuss the diagnosis, management and outcome of struma ovarii, in particular with malignant transformation. Echography objectives pelvic tumor in all cases. The diagnosis is usually histological. Treatment is exclusively surgically, all patients with malignant struma ovarii were staged la (FIGO). Mean follow up was 4 years and 4 months (range: 1-7 years). No recurrences were reported and no distant metastases. Supervision was based on serum level thyroglobuline and scintigraphy with iodine 131. Histologic diagnosis of malignancy is difficult. Treatment is based on surgery and prognosis is relatively favorable even in malignant cases.     

Angioplasty of Anomalous Coronaries Arising from the Opposite Sinus with an Interarterial Course,is it Safe?

BackgroundThe coronary artery with an interarterial course CAIAC is the most threatening coronary anomaly, especially if it concerns the left coronary. Percutaneous coronary intervention PCI is scarcely described given its low prevalence and lack of long-term outcome data. Therefore, we assessed through this case series the feasibility and safety of PCI in this population.MethodsThis is an observational multicentric study including patients with CAIAC arising from the opposite sinus of Valsalva. The primary endpoints were immediate angiographic success and target lesion revascularization.ResultsDuring the period of the study, we performed 27235 PCI in six Cath labs, 26 procedures concerning abnormal coronaries including 12 with CAIAC. The median age was 57 years extremes: 43–78 with male predominance 1:11. Anomalous coronary artery was Right coronary artery RCA in eight patients, Left main LM in three patients, and left anterior descending LAD in one patient. The stenosis was located in all cases in proximal segments beyond the inter-arterial course proximal LAD, the superior genius of the RCA, or the proximal segment of mid-RCA. Five patients showed slit-like ostium and all have an angle take-off <45° on CT scan. After a median follow-up of 24 months, four subjects presented target lesion revascularization TLR, all were initially treated with either a bare-metal stent or with balloons.ConclusionsPCI of patients with CAIAC is feasible and appears safe. The operator should carefully analyze the angiogram before PCI to choose the appropriate guiding catheter and should be acquainted with the different techniques for improving backup.