[Rheumatic cardiopathies and its risk factors: about 50 cases]. / Les complications cardiaques du rhumatisme articulaire aigu et ses facteurs de risque : étude de 50 observations.

INTRODUCTION: Acute rheumatic fever (ARF) is a multi-systemic disease, in which cardiac involvement is the most serious major manifestation of disease. The aim of this study was to analyse cardiac involvement in children with ARF and his risk factors. MATERIALS AND METHODS: It were a retrospective study including all children under the age of 14 years who were hospitalized for ARF in the pediatric department of the CHU Hédi Chaker of Sfax, during a period of twelve years (2010-2022). RESULTS: We collected 50 cases (31 boys and 19 girls). Twenty-two patients (44%) developed cardiac lesions. The mean age at diagnosis was 9.6 years [5-14 years]. A pathological heart murmur was detected in 14 cases (n = 14/22) was classified as mild carditis in 15 cases, moderate carditis in 5 cases and severe in 2 cases. The median follow-up time was 3,3 years. Nineteen patients developed valvular sequelae Risk factors of cardiac lesions was: age more than 8 years, heart murmur, allonged PR, CRP > 100 mg/l and VS > 100 mm. CONCLUSION: CR is still a public health problem in Tunisia. It is a serious pathology that can cause serious increases in morbidity rates. Thus, we must strengthen preventive strategies.

Molecular and computational characterization of ABCB11 and ABCG5 variants in Tunisian patients with neonatal/infantile low-GGT intrahepatic cholestasis: Genetic diagnosis and genotype-phenotype correlation assessment.

Many inherited conditions cause hepatocellular cholestasis in infancy, including progressive familial intrahepatic cholestasis (PFIC), a heterogeneous group of diseases with highly overlapping symptoms. In our study, six unrelated Tunisian infants with PFIC suspicion were the subject of a panel-target sequencing followed by an exhaustive bioinformatic and modeling investigations. Results revealed five disease-causative variants including known ones: (the p.Asp482Gly and p.Tyr354 * in the ABCB11 gene and the p.Arg446 * in the ABCC2 gene), a novel p.Ala98Cys variant in the ATP-binding cassette subfamily G member 5 (ABCG5) gene and a first homozygous description of the p.Gln312His in the ABCB11 gene. The p.Gln312His disrupts the interaction pattern of the bile salt export pump as well as the flexibility of the second intracellular loop domain harboring this residue. As for the p.Ala98Cys, it modulates both the interactions within the first nucleotide-binding domain of the bile transporter and its accessibility. Two additional potentially modifier variants in cholestasis-associated genes were retained based on their pathogenicity (p.Gly758Val in the ABCC2 gene) and functionality (p.Asp19His in the ABCG8 gene). Molecular findings allowed a PFIC2 diagnosis in five patients and an unexpected diagnosis of sisterolemia in one case. The absence of genotype/phenotype correlation suggests the implication of environmental and epigenetic factors as well as modifier variants involved directly or indirectly in the bile composition, which could explain the cholestasis phenotypic variability.

Preparation and Characterization of New and Low-Cost Ceramic Flat Membranes Based on Zeolite-Clay for the Removal of Indigo Blue Dye Molecules.

Composite flat membranes were prepared using a dry uniaxial pressing process. The effect of the sintering temperature (850-950 °C) and smectite proportion (10-50 wt.%) on membrane properties, such as microstructure, mechanical strength, water permeability, and treatment performances, was explored. It was observed that increasing the sintering temperature and adding higher amounts of smectite increased the mechanical strength and shrinkage. Therefore, 850 °C was chosen as the optimum sintering temperature because the composite membranes had a very low shrinkage that did not exceed 5% with high mechanical strength, above 23 MPa. The study of smectite addition (10-50 wt.%) showed that the pore size and water permeability were significantly reduced from 0.98 to 0.75 µm and from 623 to 371 L·h-1·m-2·bar-1, respectively. Furthermore, the application of the used membranes in the treatment of indigo blue (IB) solutions exhibited an almost total turbidity removal. While the removal of color and COD decreased from 95% to 76%, respectively, they decreased from 95% to 52% when the amount of smectite increased. To verify the treated water's low toxicity, a germination test was performed. It has been shown that the total germination of linseed grains irrigated by MS10-Z90 membrane permeate was identical to that irrigated with distilled water. Finally, based on its promising properties, its excellent separation efficiency, and its low energy consumption, the MS10-Z90 (10 wt.% smectite and 90 wt.% zeolite) sintered at 850 °C could be recommended for the treatment of colored industrial wastewater.

Clinical and therapeutic characteristics of childhood uveitis in a tertiary center in Tunisia.

INTRODUCTION: Childhood uveitis is a rare condition with various associated diagnostic and therapeutic challenges. AIM: We proposed to describe the distribution, clinical findings, treatment, complications, and visual outcomes of uveitis in children at a tertiary referral center in Sfax, Tunisia. METHODS: A retrospective study of 33 children (54 eyes) with uveitis collected over the period from January 2009 to December 2018 was carried out at the Ophthalmology Department of Habib Bourguiba University Hospital, Sfax, Tunisia. The data from the clinical examination, the etiological assessment, and the used treatments were collected. Standard diagnostic criteria were used for all uveitic syndromes or entities. RESULTS: The mean age of the patients was 11.42 years with a male-to-female ratio of 0.74. Uveitis was bilateral in 63% of the patients. The most common anatomical form was intermediate uveitis (39%). Idiopathic cases accounted for 52%. The major complications were posterior synechiae, optic disc edema, cataract, and cystoid macular edema. Anti-infective treatment was prescribed in 24% of the patients. Oral corticosteroid therapy was used in 67% of the patients. 18% of the patients received immunosuppressive therapy and 6% received a biological agent. The mean final visual acuity was 4.6/10. CONCLUSION: Childhood uveitis is a serious pathology with frequent and vision-threatening complications. The etiologies are variable and the assessment can remain negative. A rigorous diagnostic approach, an oriented etiological assessment in collaboration with the pediatrician, and an appropriate therapy are necessary for management.

Development of Ultrafiltration Kaolin Membranes over Sand and Zeolite Supports for the Treatment of Electroplating Wastewater.

A high cost of high-purity materials is one of the major factors that limit the application of ceramic membranes. Consequently, the focus was shifted to using natural and abundant low-cost materials such as zeolite, clay, sand, etc. as alternatives to well-known pure metallic oxides, such as alumina, silica, zirconia and titania, which are usually used for ceramic membrane fabrication. As a contribution to this area, the development and characterization of new low-cost ultrafiltration (UF) membranes made from natural Tunisian kaolin are presented in this work. The asymmetric ceramic membranes were developed via layer-by-layer and slip-casting methods by direct coating on tubular supports previously prepared from sand and zeolite via the extrusion process. Referring to the results, it was found that the UF kaolin top layer is homogenous and exhibits good adhesion to different supports. In addition, the kaolin/sand and kaolin/zeolite membranes present an average pore diameter in the range of 4-17 nm and 28 nm, and water permeability of 491 L/h·m2·bar and 182 L/h·m2·bar, respectively. Both membranes were evaluated in their treatment of electroplating wastewater. This was done by removing oil and heavy metals using a homemade crossflow UF pilot plant operated at a temperature of 60 °C to reduce the viscosity of the effluent, and the transmembrane pressure (TMP) of 1 and 3 bar for kaolin/sand and kaolin/zeolite, respectively. Under these conditions, our membranes exhibit high permeability in the range of 306-336 L/h·m2·bar, an almost total oil and lead retention, a retention up to 96% for chemical oxygen demand (COD), 96% for copper and 94% for zinc. The overall data suggest that the developed kaolin membranes have the potential for remediation of oily industrial effluents contaminated by oil and heavy metals.

Treatment of Tuna Cooking Juice via Ceramic Ultrafiltration Membrane: Optimization Using Response Surface Methodology.

In the present work, optimized ultrafiltration conditions, using a ceramic multi tubular titania membrane (150 KDa), were investigated for the treatment of tuna cooking juice, for water reuse in the industrial process. The interactive effects of the volume concentrating factor (VCF) (1.03-4.25), feed temperature (T) (20-60 °C), and applied transmembrane pressure (ΔP) (2-5 bar) on protein removal (R protein) and permeate flux (J) were determined. A Box-Behnken experimental design (BBD) with the response surface methodology (RSM) was used for statistical analysis, modeling, and optimization of the operating conditions. The analysis of variance (ANOVA) results proved that the protein removal and permeate flux were significant and represented good correlation coefficients of 0.9859 and 0.9294, respectively. Mathematical modeling showed that the best conditions were VCF = 1.5 and a feed temperature of 60 °C, under a transmembrane pressure of 5 bar. The fouling mechanism was checked by applying a polarization concentration model. Determination of the gel concentration confirmed the results found in the mass balance calculation and proved that the VCF must not exceed 1.5. The membrane regeneration efficiency was proven by determining the water permeability after the chemical cleaning process.

Statistical Simulation, a Tool for the Process Optimization of Oily Wastewater by Crossflow Ultrafiltration.

This work aims to determine the optimized ultrafiltration conditions for industrial wastewater treatment loaded with oil and heavy metals generated from an electroplating industry for water reuse in the industrial process. A ceramic multitubular membrane was used for the almost total retention of oil and turbidity, and the high removal of heavy metals such as Pb, Zn, and Cu (>95%) was also applied. The interactive effects of the initial oil concentration (19−117 g/L), feed temperature (20−60 °C), and applied transmembrane pressure (2−5 bar) on the chemical oxygen demand removal (RCOD) and permeate flux (Jw) were investigated. A Box−Behnken experimental design (BBD) for response surface methodology (RSM) was used for the statistical analysis, modelling, and optimization of operating conditions. The analysis of variance (ANOVA) results showed that the COD removal and permeate flux were significant since they showed good correlation coefficients of 0.985 and 0.901, respectively. Mathematical modelling revealed that the best conditions were an initial oil concentration of 117 g/L and a feed temperature of 60 °C, under a transmembrane pressure of 3.5 bar. In addition, the effect of the concentration under the optimized conditions was studied. It was found that the maximum volume concentrating factor (VCF) value was equal to five and that the pollutant retention was independent of the VCF. The fouling mechanism was estimated by applying Hermia's model. The results indicated that the membrane fouling given by the decline in the permeate flux over time could be described by the cake filtration model. Finally, the efficiency of the membrane regeneration was proved by determining the water permeability after the chemical cleaning process.

Custom Next-Generation Sequencing Identifies Novel Mutations Expanding the Molecular and clinical spectrum of isolated Hearing Impairment or along with defects of the retina, the thyroid, and the kidneys.

BACKGROUND: In the Tunisian population, the molecular analysis of hearing impairment remains based on conventional approaches, which makes the task laborious and enormously expensive. Exploration of the etiology of Hearing Impairment and the early diagnosis of causal mutations by next-generation sequencing help significantly alleviate social and economic problems. METHODS: We elaborated a custom SureSelectQXT panel for next-generation sequencing of the coding sequences of 42 genes involved in isolated hearing impairment or along with defects of the retina, the thyroid, and the kidneys. RESULTS: We report eight pathogenic variants, four of which are novel in patients with isolated hearing impairment, hearing impairment, and renal tubular acidosis, Usher syndrome and Pendred syndrome. Functional studies using molecular modeling showed the severe impact of the novel missense mutations on the concerned proteins. Basically, we identified mutations in nuclear as well as mitochondrial genes in a Tunisian family with isolated hearing impairment, which explains definitely the phenotype detected since 2006. CONCLUSION: Our results expanded the mutation spectrum and genotype-phenotype correlation of isolated and syndromic hearing loss and also emphasized the importance of combining both targeted next-generation sequencing and detailed clinical evaluation to elaborate a more accurate diagnosis for hearing impairment and related phenotypes especially in North African populations.

8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects.

BACKGROUND: 8q21.11 microdeletion syndrome is a rare chromosomal disorder characterized by recurrent dysmorphic features, a variable degree of intellectual disability and ocular, cardiac and hand/feet abnormalities. To date, ZFHX4 is the only candidate gene implicated in the ocular findings. In this study, we evaluated a patient with a de novo 8q21.13-21.3 deletion to define a new small region of overlap (SRO) for this entity. METHODS: We conducted a clinical evaluation and comparative genomic hybridization (CGH) 4x44K microarrays in a patient with de novo unbalanced translocation t(8;16)(q21; q11.2). RESULTS: The case, a 6-year-old boy, presented dysmorphic features including an elongated face, brachycephaly with a high forehead, an underdeveloped ala, thin upper lip, micrognathia, low-set ears, hypotonia, mild intellectual disability, cortical atrophy with thin corpus callosum defect, and an atrial septal defect. No ocular abnormalities were found. Microarray analysis revealed a 9.6 Mb interstitial 8q21.11-21.3 deletion, not including the ZFHX4 gene. This microdeletion was confirmed in our patient through qPCR analysis, and both parents had a normal profile. Alignment analysis of our case defined a new SRO encompassing five genes. Among them, the HEY1 gene is involved in the embryonic development of the heart, central nervous system, and vascular system. Hrt1/Hey1 null mice show perinatal lethality due to congenital malformations of the aortic arch and its branch arteries. HEY1 has also been linked to the maintenance of neural stem cells, inhibition of oligodendrocyte differentiation, and myelin gene expression. CONCLUSION: HEY1 is a candidate gene for both neurological and cardiac features of the 8q21.11 microdeletion syndrome and might, therefore, explain specific components of its pathophysiology.

Removal of fluoride ions (F-) from aqueous solutions using modified Turkish zeolite with quaternary ammonium.

The natural Turkish zeolite has been modified with hexadecyltrimethylammonium bromide (CTAB) for the elimination of fluoride (F-) from aqueous solutions. The parent natural zeolite (NZ) and modified zeolite (MZ) have been characterized by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), zeta potentials and Brunauer-Emmett-Teller (BET) method. The effect of pH, adsorbent dose, contact time, initial concentration and temperature on adsorption of fluoride ions onto modified zeolite (MZ) has been determined in batch experiments. Fluoride concentration can be reduced to 1.5 mg/L under the optimum condition (pH = 5, adsorbent dose = 20 mg/L, contact time = 60 min and T = 293 K) when initial fluoride concentration of 10 mg/L is employed. The fluoride adsorption on MZ has been described by the Langmuir isotherm and the maximum fluoride adsorption capacity was found as 2.994 mg/g. Kinetics data were best described by the pseudo-second-order model. The thermodynamic studies proved that the adsorption was exothermic and spontaneous.

Mutations in GAA Gene in Tunisian Families with Infantile Onset Pompe Disease: Novel Mutation and Structural Modeling Investigations.

Pompe disease, a rare, autosomal, recessive, inherited, lysosomal storage disorder, is caused by mutations in the acid α-glucosidase (GAA) gene leading to a deficiency of the lysosomal GAA enzyme. Some GAA mutations eliminate all enzymatic activities, causing severe infantile Pompe disease; others allow residual GAA activity and lead to middle adulthood forms. Here, we report a cohort of 12 patients, belonging to 11 unrelated families, with infantile Pompe disease. The mutational analysis of GAA gene revealed a novel c.1494G > A (p.Trp498X) mutation in one patient and three known mutatio,ns including the c.1497G > A (p.Trp499X) mutation, in two patients, the c.1927G > A (p.Gly643Arg) mutation in one patient and the common c.236_246del (p.Pro79ArgfsX13) mutation in eight patients. The high prevalence of c.236_246del mutation in our cohort (58%) was supported by the existence of a common founder ancestor that was confirmed by its segregation of similar SNPs haplotype, including four intragenic SNPs of GAA gene. In addition, a 3D structure model and a docking were generated for the mutant p.Gly643Arg using the crystal structure of human GAA as template and the 4-methylumbelliferyl-α-D-glucopyranoside as substrate. The results showed that the arginine at position 643 caused electrostatic changes in neighboring regions, leading to the repulsion between the amino acids located in the catalytic cavity of the GAA enzyme, thus restricting access to its substrate. These structural defects could cause the impairment of the transport and maturation previously reported for p.Gly643Arg mutation.

[Epidemiology of home accidents in childhood: experience in the Division of General Pediatrics in Southern Tunisia]. / Epidémiologie des accidents domestiques de l'enfant: expérience d'un Service de Pédiatrie Générale du sud tunisien.

Home accidents are a serious public health problem in Pediatrics. They are responsible for heavy morbidity and mortality in the paediatric population. We conducted a retrospective study of 231 cases of domestic accidents in childhood in the Division of General Pediatrics at the Hedi Chaker Hospital, Sfax over a period of 5 years (2008-2012). During the study period, we collected data from 231 domestic accidents. The study involved 124 boys (53.7 %) and 107 girls (46.3%). The average age of patients was 2 years, ranging from 1 day to 14 years; children under 4 years were the most exposed to home accidents (88.7%). Accidental poisonings were the most common accidents (105 cases). Caustics were the most common toxic agents (33 cases), followed by drugs (28 cases) and hydrocarbons (16 cases). Foreign body accidents were the second most common mechanism of injury (64 cases). They included 43 cases of inhalation of foreign bodies and 21 cases of foreign body ingestion. We recorded 28 cases of trauma, 25 cases were caused by a fall from a certain height. We noted 26 cases of scorpion envenomation, 5 cases of drowning, 2 cases of burn and a single case of electric shock. Accidental poisonings and foreign body accidents were the main home accidents noted during our study and the age group 1 -4 years was the most exposed to home accidents.

Hypoparathyroidism in children: a study of eight cases.

BACKGROUND: Hypoparathyroidism is a rare pediatric endocrine disease, which is caused by low circulating levels of PTH or insensitivity to its action in the target tissues. AIM: To report the clinical and biochemical characteristics and theoutcome of 8 patients with hypoparathyroidism. METHODS: We analyzed retrospectively the results of clinical, biochemical, radiological findings of patients with hypoparathyroidism diagnosed in pediatric department of Hedi Chaker Hospital during the period 1994-2013. RESULTS: Eight patients (5 females and 3 males) were diagnosed with hypoparathyroidism during 20 years's period. The median age at the onset of first symptoms was 17,5 months (15 days- 5 years and 10 months). Seizures were the most commonly presenting symptom and were seen in seven cases. Eight patients were diagnosed with hypoparathyroidism (Di-Georges syndrome: one case, Sanjad Sakati syndrome: 3 case, kearns sayre syndrome: 1 case, autoimmune polyendocrinopathy candidiasis- ectodermal dystrophy: one case, idiopathic hypoparathyroidism: two cases. Conventional treatment was based on calcium and vitamin D analogs. The average of follow up was 5 years. Nephrocalcinosis was noted in two patients. The death occurred in five patients; it was related to hypocalcaemia in one patient. CONCLUSION: The diagnosis of hyperparathyroidism is easy; it's established on the association of hypocalcaemia and hyperphosphatemia. Etiologic approach is based on molecular findings. Vitamin D analog treatment of hypoparathyroidism in children involves the challenge, of adjusting treatment dosage to minimize both symptomatic hypocalcemia and asymptomatic, but potentially kidney-damaging, hypercalciuria causing nephrocalcinosis and renal insufficiency.

Adverse Reactions Due to the Bacillus Calmette-Guerin Vaccine: Twenty Tunisian Cases.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccine is a widely used vaccine. Management of local BCG complications differs between clinicians, and the optimal approach remains unclear. AIMS: We aim to describe the epidemiological, clinical and therapeutic aspects of the BCG vaccine side effects in Sfax. PATIENTS AND METHODS: This was a retrospective study of all the cases of BCG vaccine adverse reactions recorded in the Dermatology and Paediatrics Departments of Hedi Chaker University Hospital of Sfax over a period of 10 years (2005-2015). RESULTS: Twenty cases of BCG adverse reactions were notified during the study period. Actually, 80% of the patients presented local adverse reactions. The outcome was good in all the followed patients. The rate of disseminated BCG disease was 20%. Biological tests of immunity showed a primary immunodeficiency in three cases, whereas the outcome was fatal in two cases. CONCLUSION: BCG vaccine adverse reactions range from mild to severe. However, the management of benign local reactions remains unclear. Disseminated BCG disease must alert clinicians to the possibility of a primary immunodeficiency.

Factor XIII deficiency in south of Tunisia.

: Factor XIII deficiency is a rare autosomal recessive disorder of hemostasis characterized by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. The aim of the study is to describe the clinical features and the outcome of the patients and to determine molecular characteristics. A retrospective study, was conducted on seven patients with factor XIII deficiency in the department of hematology and pediatrics, Hedi Chaker Hospital, Sfax, Tunisia during the period of 14 years (2001-2014). The activity of factor XIII in plasma of the patients was less than 1%. Seven patients from five unrelated families were recorded (four men and three women). Median age at diagnosis was 3.5 years. All patients had consanguineous parents. Six patients presented umbilical bleeding and only three patients had intracranial bleeding. Other bleeding features were seen, including skin and mucosal bleeding, muscular hematoma, and splenic rupture. Recurrent abortions were observed in one patient. The standard screening tests were normal. Genetic analysis identified two mutations interesting the subunit A of factor XIII. All patients received transfusion of fresh frozen plasma monthly. One patient was died because of intracranial hemorrhage.Factor XIII deficiency is a rare bleeding disorder which frequently increases in areas with high consanguinity. In our study, we identified a founder mutation. The prognosis of the disorder is related to hemorrhagic complications especially to life-threatening intracranial bleeding. Prophylaxis consists of factor XIII concentrate or recombinant factor XIII. If these are unavailable, fresh frozen plasma may be used.

Clinical and Genetic Characterization of Tunisian Children with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets.

BACKGROUND: Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by the early onset of rickets and is caused by mutations in the vitamin D receptor (VDR) gene. Some HVDRR patients also have alopecia. PATIENTS AND METHODS: We retrospectively studied the clinical features, laboratory findings, genetic defects, as well as responses to treatment in a series of children with HVDRR. RESULTS: Eight patients from 7 families met the inclusion criteria. Alopecia was noted in 7 patients. Two different homozygous mutations in the VDR gene were identified in 6 patients: the p.K45E mutation located in the DNA-binding domain (5 patients with alopecia) and a novel p.T415R mutation located in the ligand-binding domain. A p.E143del CYP24A1 mutation, in the gene encoding the 25-hydroxyvitamin D3-24-hydroxylase, was identified in 2 brothers carrying the VDR gene mutation p.K45E. Six patients were treated with intermittent intravenous calcium treatment via the peripheral route with a clear improvement in 5 cases. CONCLUSION: To the best of our knowledge, this is the first major series reporting on HVDRR in Tunisia. The same mutation (p.K45E) was found in 5 apparently unrelated affected individuals. We have also extended the mutation spectrum by studying 1 novel VDR mutation.

Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome.

BACKGROUND AND AIMS: Allgrove syndrome is characterized by achalasia, alacrima, and adrenal insufficiency as well as being associated with progressive neurological signs. This is an autosomal recessive disorder due to mutations in the AAAS gene located on chromosome 12q13. The AAAS gene encodes a protein of 546 amino acids, ALADIN. Mutations in this genwere reported in families from North Africa and Europe. Our objective is to conduct a clinical, molecular and genetic study of 26 Tunisian patients with Allgrove syndrome. METHODS: We report 26 Tunisian patients with between two and four clinical features associated with Allgrove syndrome. Blood samples were collected and isolated DNA derived from subjects was amplified. The entire sequence of the AAAS gene was analyzed by PCR and sequencing. PCR-RFLP method was performed to identify the frequent mutations found. RESULTS: Sequencing of the AAAS gene revealed a major homozygous mutation (c.1331+1G>A) in 25 patients and R286X mutation in one patient. The presence of a major mutation in several unrelated affected individuals suggests the presence of a founder effect in Tunisia and allows for a fast and targeted molecular diagnosis. CONCLUSIONS: We created an easy and rapid molecular enzymatic protocol based on PCR-RFLP using MvaI restriction enzyme that directly targets this major mutation and can be used for prenatal diagnosis and genetic counseling for Tunisian families at risk. To the best of our knowledge, this is the first major series report of Allgrove syndrome in Tunisia.