Analysis of MHC genes in a Tunisian isolate with autoimmune thyroid diseases: implication of TNF -308 gene polymorphism

Autoimmune thyroid diseases (AITDs), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized as multifactorial diseases. In this study, we have examined single and haplotypic genetic variation across the major histocompatibility complex (MHC) in a Tunisian isolate with a high prevalence of AITDs (62 patients: 32 with GD, 9 with HT and 21 with PIM). Genotyping was performed for HLA class I and II alleles as well as polymorphisms within tumor necrosis factor (TNF), lymphotoxin alpha (TLalpha) and heat shock protein (HSP70-02 and HSP70-hom) genes. Our results showed association of HLA-A2-B50-TNF 2 haplotype with AITDs (p = 0.045). Linkage analysis using Simwalk2 program has shown significant result with TNF -308 gene polymorphism (p = 0.03). The FBAT has given evidence for genetic association with TNF -308 and HLA-DR gene polymorphisms. TNF 2 allele was associated with GD (p = 0.0011), whereas TNF 1, HLA-DR11 and DR12 (p = 0.0039, p = 0.00089 and p = 0.0056, respectively) were rather implicated in HT pathogenesis. Results found by TDT-STDT have confirmed the involvement of the TNF -308 gene polymorphism in AITD pathogenesis (p < 10(-9)).     

Prevalence of malocclusions and orthodontic treatment need in 8- to 12-year-old schoolchildren in Casablanca,Morocco

ObjectivesThe purpose of this work was to evaluate the prevalence of malocclusions and orthodontic treatment need among schoolchildren in Casablanca, Morocco.Materials and methodsA sample of 1000 children aged between 8 and 12 years, with no history of orthodontic treatment, was chosen at random in state schools in different administrative areas of the city of Casablanca. Data was registered using the method of Bjork et al. (1964). Orthodontic treatment need was assessed with the index used by the Swedish National Board of Health (SweNBH).ResultsWe found Angle Class I malocclusions in 61.4%, Class II in 24%, Class III in 10% and an indeterminate molar class with one or more missing molars in 4.6% of the children. Overjet was 1–4 mm in 63.8%, 4–6 mm in 17.2% and >6 mm in 10%. Bite was normal in 65.4%, 23.6% presented an overbite greater than 4 mm, 1.7% an anterior open bite ≤3 mm, 1.2% an anterior open bite >3 mm and 0.2% a bilateral open bite. Half of the sample presented anterior crowding, while only 2.5% presented posterior crowding. In all, 84.2% of the subjects needed some orthodontic treatment, and 15.8% needed no treatment. No statistically significant difference was found between sex or age and orthodontic treatment need (P>0.05).ConclusionsThis study found a strong need for orthodontic treatment, confirming the utility of implementing a programme of bucco-dental prevention and screening for malocclusion.     

Dissociation of the Role of Infralimbic Cortex in Learning and Consolidation of Extinction of Recent and Remote Aversion Memory

Medial prefrontal circuits have been reported to undergo a major reorganization over time and gradually take a more important role for remote emotional memories such as contextual fear memory or food aversion memory. The medial prefrontal cortex, and specifically its ventral subregion, the infralimbic cortex (IL), was also reported to be critical for recent memory extinction of contextual fear conditioning and conditioned odor aversion. However, its exact role in the extinction of remotely acquired information is still not clear. Using postretrieval blockade of protein synthesis or inactivation of the IL, we showed that the IL is similarly required for extinction consolidation of recent and remote fear memory. However, in odor aversion memory, the IL was only involved in extinction consolidation of recent, but not remote, memory. In contrast, only remote retrieval of aversion memory induced c-Fos activation in the IL and preretrieval inactivation of the IL with lidocaine impaired subsequent extinction of remote but not recent memory, indicating IL is necessary for extinction learning of remote aversion memory. In contrast to the effects in odor aversion, our data show that the involvement of the IL in the consolidation of fear extinction does not depend on the memory age. More importantly, our data indicate that the IL is implicated in the extinction of fear and nonfear-based associations and suggest dissociation in the engagement of the IL in the learning and consolidation of food aversion extinction over time.     

Description of response to aspirin and clopidogrel in outpatients with coronary artery disease using multiple electrode impedance aggregometry

Identification of outpatients with high platelet reactivity (HPR) on antiplatelet treatment is an unmet need. The present study was conducted in healthy individuals (n = 50) and in outpatients with coronary artery disease (CAD) at a distance from the acute ischemic episode (aspirin group, n = 71; aspirin/clopidogrel group, n = 106). We studied the feasibility and the precision of whole blood multiple electrode aggregometry (MEA) after triggering platelet aggregation by arachidonic acid or adenosine diphospate (ADP). The MEA can be performed on whole blood within 2 hours after sample venipuncture. The threshold for the diagnosis of HPR is situated at 55 and 50 U for the arachidonic acid and ADP test, respectively. Frequency of HPR was 7% and 20% in aspirin and aspirin/clopidogrel groups, respectively. In 3.8% of patients in aspirin/clopidogrel group, combined HPR on aspirin and clopidogrel was found. In outpatients with CAD, use of MEA is feasible for the diagnosis of HPR.     

Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1

COL1A1 haploinsufficiency mutations lead to the mildest form of osteogenesis imperfecta (OI), OI type I. The skeletal clinical characteristics resulting from such mutations have not been characterized in detail. In this study we assessed 86 patients (36 male, 50 female; mean age 13.3 years; range, 0.6 to 54 years) with COL1A1 haploinsufficiency mutations, of whom 70 were aged 21 years or less (“pediatric” patients). Birth history was positive for fracture or long‐bone deformity in 12% of patients. The average rate of long‐bone fracture (femur, tibia/fibula, humerus, radius/ulna) in pediatric patients was 0.62 fractures per year, one‐half of which affected the tibia/fibula. Long‐bone fracture rate was negatively associated with age and lumbar spine areal bone mineral density. Vertebral compression fractures were observed in 71% of the 58 pediatric patients who had lateral spine radiographs. The median number of vertebral fractures was higher for females (median 4; range, 0 to 14) than for males (median 1; range, 0 to 8) (p = 0.03). Lumbar spine areal bone mineral density was negatively associated with the severity of vertebral compression fractures, as reflected in the spine deformity index. Scoliosis was present in about 30% of pediatric patients but the Cobb angle was <30 degrees in all cases. The average final height Z‐score was –1.1, representing a deficit of 8 to 10 cm compared to the general population. In summary, OI patients with COL1A1 haploinsufficiency mutations have high rates of significant skeletal involvement. Systematic follow‐up of growing patients with COL1A1 haploinsufficiency mutations including radiographic screening for vertebral compression fractures and scoliosis is warranted.