A novel integrative multi-omics approach to unravel the genetic determinants of rare diseases with application in sinusoidal obstruction syndrome.

Background: Genotype-phenotype analyses of rare diseases often suffer from a lack of power, due to small sample size, which makes identifying significant associations difficult. Sinusoidal obstruction syndrome (SOS) of the liver is a rare but life-threatening complication of hematopoietic stem cell transplantation (HSCT). The alkylating agent busulfan is commonly used in HSCT and known to trigger SOS.

Evaluation of Growing Wild in Tunisia for Its Potential as a Dietary Supplement.

L., known as horehound, is a widespread and widely known plant that is used in beer breweries and also as a traditional remedy in Tunisia. In this study, methanolic extracts of plants harvested from five different locations were investigated for their antioxidant activities using three assays (ferric reducing power, radical scavenging activity, and -carotene-linoleic acid bleaching assay) as well as the total phenolic content.

Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation.

Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function.

GSTM1 and GSTT1 double null genotypes determining cell fate and proliferation as potential risk factors of relapse in children with hematological malignancies after hematopoietic stem cell transplantation.

Purpose: This study aimed to retrospectively evaluate the genetic association of null variants of glutathione S-transferases GSTM1 and GSTT1 with relapse incidence in children with hematological malignancies (HMs) undergoing busulfan (BU)- containing allogeneic hematopoietic stem cell transplantation (HSCT) and to assess the impact of these variants on BU-induced cytotoxicity on the immortalized lymphoblastoid cell lines (LCLs) and tumor THP1 GST gene-edited cell models.

Methods: GSTM1- and GSTT1-null alleles were genotyped using germline DNA from whole blood prior to a conditioning BU-based regimen. Association of GSTM1- and GSTT1-null variants with relapse incidence was analyzed using multivariable competing risk analysis.

Is Busulfan Clearance Different in Patients With Sickle Cell Disease? Let's Clear Up That Case With Some Controls.

In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination. This pharmacokinetics study assesses the influence of SCD on the metabolic pathway of busulfan that is mainly metabolized in the liver.

Modelling, Analysis, and Optimization of the Effects of Pulsed Electrophoretic Deposition Parameters on TiO Films Properties Using Desirability Optimization Methodology.

Titanium dioxide thin films immobilized over treated stainless steel were prepared using the pulsed electrophoretic deposition technique. The effects of process parameters (deposition time, applied voltage, initial concentration, and duty cycle) on photocatalytic efficiency and adhesion properties were investigated. To optimize the multiple properties of the thin film, a response surface methodology was combined with a desirability optimization methodology.

Antioxidant and antifungal activities of marrubiin, extracts and essential oil from Marrubium vulgare L. against pathogenic dermatophyte strains.

Objective: Medicinal plants extracts and plant-derived compounds are one of the natural sources for discovering new antifungal agents, the objectives of this work were to investigate for the first time the antidermatophytic, antipathogenic activities of methanol, acetone extracts, and essential oil of Marrubium vulgare L. grown in Tunisia and its active compound marrubiin on pathogenic for animals and humans, such as some dermatophytes and pathogenic for plants, and to evaluate antioxidant activities of different extracts with consideration to their chemical compositions.

Material And Methods: Acetone and methanol extracts were evaluated by HPLC, the essential oil was also analyzed by GC/MS.

Incorporation of GSTA1 genetic variations into a population pharmacokinetic model for IV busulfan in paediatric hematopoietic stem cell transplantation.

Aims: The aim of this study is to develop a population pharmacokinetic (PopPK) model for intravenous busulfan in children that incorporates variants of GSTA1, gene coding for the main enzyme in busulfan metabolism.

Methods: Busulfan concentration-time data was collected from 112 children and adolescents (median 5.4 years old, range: 0.

GSTA1 diplotypes affect busulfan clearance and toxicity in children undergoing allogeneic hematopoietic stem cell transplantation: a multicenter study.

Busulfan (BU) dose adjustment following therapeutic drug monitoring contributes to better outcome of hematopoietic stem cell transplantation (HSCT). Further improvement could be achieved through genotype-guided BU dose adjustments. To investigate this aspect, polymorphism within glutathione S transferase genes were assessed.

GSTA1 Genetic Variants and Conditioning Regimen: Missing Key Factors in Dosing Guidelines of Busulfan in Pediatric Hematopoietic Stem Cell Transplantation.

Busulfan (Bu) is a key component of conditioning regimens used before hematopoietic stem cell transplantation (SCT) in children. Different predictive methods have been used to calculate the first dose of Bu. To evaluate the necessity of further improvements, we retrospectively analyzed the currently available weight- and age-based guidelines to calculate the first doses in 101 children who underwent allogenic SCT in CHU Sainte-Justine, Montreal, after an intravenous Bu-containing conditioning regimen according to genetic and clinical factors.

Association of CTH variant with sinusoidal obstruction syndrome in children receiving intravenous busulfan and cyclophosphamide before hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) is a severe complication of hematopoietic stem cell transplantation (HSCT) that can be fatal, often attributed to the conditioning regimen prior to HSCT. We evaluated the association of SOS risk with gene variants in cystathionase (CTH), an enzyme involved in glutathione synthesis, in 76 children receiving intravenous busulfan (Bu) before HSCT. Our results indicated an association with CTHc.

Influence of glutathione S-transferase gene polymorphisms on busulfan pharmacokinetics and outcome of hematopoietic stem-cell transplantation in thalassemia pediatric patients.

Hematopoietic stem-cell transplantation (HSCT) is currently the only curative therapeutic option for the treatment of thalassemia. In spite of the high cure rate, HSCT can lead to life-threatening adverse events in some patients. Busulfan (Bu) is a key component of the conditioning regimen prior to HSCT.

Periodic variation of the water use efficiency in durum wheat.

Water Use Efficiency (WUF) of five durum wheat varieties (Khiar, Karim, Nasr, Razzak and Sobirano) cultivated in Tunisia was investigated. The experiment was conducted under rainfed field conditions, irrigated pots and test tubes at ESA Kef experiment station during the cropping season of 2010-2011. Under rainfed conditions, Khiar has the highest grain yield with 29.

The association of cytochrome P450 genetic polymorphisms with sulfolane formation and the efficacy of a busulfan-based conditioning regimen in pediatric patients undergoing hematopoietic stem cell transplantation.

Cytochrome P450 enzymes (CYPs) and flavin-containing monooxygenases (FMOs) likely have a role in the oxidation of intermediate metabolites of busulfan (Bu). In vitro studies to investigate the involvement of these enzymes are cumbersome because of the volatile nature of the intermediate metabolite tetrahydrothiophene (THT) and the lack of sensitive quantitation methods. This study explored the association between the CYP2C9, CYP2C19, CYP2B6 and FMO3 genotypes and sulfolane (Su, a water soluble metabolite of Bu) plasma levels in children undergoing hematopoietic stem cell transplantation (HSCT).

Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematopoietic stem cell transplantation.

Background And Objective: Intravenous (IV) busulfan (Bu) combined with therapeutic drug monitoring-guided dosing is associated with better event-free survival (EFS), lower transplant-related mortality. But optimal target steady-state concentration (Css) of Bu in children undergoing hematopoietic stem cell transplantation (HSCT) remains unclear. This study aimed to evaluate the relation between Css of Bu and clinical outcomes in children receiving Bu before HSCT.

Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients.

BU is a key compound of conditioning regimens in children undergoing hematopoietic SCT (HSCT). Inter-individual differences in BU pharmacokinetics (PKs) might affect BU efficacy and toxicity. As BU is mainly metabolized by glutathione S-transferase (GST), we investigated the relationship between GSTA1, GSTM1 and GSTP1 genotypes with first-dose BU PKs, and the relationship with HSCT outcomes in 69 children receiving myeloablative conditioning regimen.

[Functioning of a university hospital emergency department].

Background: The emergency department is the part of the hospital where patients with undifferentiated emergencies are triaged and receive their initial resuscitation and treatment. It provides a 24/7 service with doctors and nurses trained in emergency medicine.

Aim: We describe our emergency department and its activity to emphasize the difficulties and try to suggest a better emergency department organization.

Incidence of deep venous thrombosis in patients with erysipelas of the leg: prospective study of 30 cases in an emergency department.

The treatment of lower limb erysipelas is based on anti-streptococcal antibiotherapy. The indication of adjuvant anticoagulant therapy is not clear because of the lack of data about the incidence of deep venous thrombosis (DVT) in these patients. We performed a prospective study using a colour Doppler vein exploration combined with ultrasonography within the first 48 h, with evaluation of clinical probability of DVT according to the Wells score to assess the incidence of DVT in patients with erysipelas of the lower limb.

[Calcification following intradiscal injection, a continuing problem?].

Introduction: Intradiscal injection of triamcinolone hexacetonide, used to treat sciatica caused by herniated discs was discontinued after discovery that it was followed in some cases by epidural calcification.

Observation: Ten years after an intradiscal injection at L4-L5, a 40 year-old man developed voluminous perivertebral, bilateral foraminal and intraductal calcifications that compressed the dural sheath. After preliminary excision, these calcifications recurred and required further excision, followed by posterior lateral grafting and osteosynthesis.

[Evaluation of outcome of patients hospitalized after pre-hospital cardiac arrest].

The aim of this study was to assess management of patients resuscitated after pre-hospital cardiac arrest, initially indicated to preserve neurological status, the aetiological investigation only being undertaken when the outcome is favourable. Eighty-nine pre-hospital cardiac arrests were analysed retrospectively. The hospital survival was 16%, death being due to neurological lesions (55%), uncontrollable haemodynamic instability -39%) or other causes (7%).