Position paper from the IBRA Symposium on Surgery of the Head - The 2nd International Symposium for Condylar Fracture Osteosynthesis, Marseille, France 2012

Background: This is a position paper from the 2nd International Bone Research Association (IBRA) Symposium for Condylar Fracture Osteosynthesis 2012 was held at Marseille, succeeding the first congress in Strasbourg, France, in 2007. The goal of this IBRA symposium and this paper was to evaluate current trends and potential changes of treatment strategies for mandibular condylar fractures, which remain controversial over the past decades.Methods: Using a cross-sectional study design, we enrolled the consensus based on the panel of experts and participants in the IBRA Symposium 2012. The outcomes of interest were the panel and electronic votes on management of condylar base, neck and head fractures, and panel votes on endoscopic and paediatric condylar fractures. Appropriate descriptive and univariate statistics were used.Results: The consensus derived from 14 experts and 41 participant surgeons, using 12 case scenarios and 27 statements. The experts and participants had similar decision on the treatment of condylar base, neck and head fractures, as well as similar opinion on complications of condylar fracture osteosynthesis. They had a parallel agreement on using open reduction with internal fixation (ORIF) as treatment of choice for condylar base and neck fractures in adults. Endoscopic approaches should be considered for selected cases, such as condylar base fractures with lateral displacement. There was also a growing tendency to perform ORIF in condylar head fractures. The experts also agreed to treat children (> 12 years old) in the same way as adults and to consider open reduction in severely displaced and dislocated fractures even in younger children. Nevertheless, non-surgical treatment should be the first choice for children <6 years of age. The decision to perform surgery in children was based on factors influencing facial growth, appropriate age for ORIF, and disagreement to use resorbable materials in children.Conclusions: The experts and participating surgeons had comparable opinion on management of condylar fractures and complications of ORIF. Compared to the first Condylar Fracture Symposium 2007 in Strasbourg, ORIF may now be considered as the gold standard for both condylar base and neck fractures with displacement and dislocation. Although ORIF in condylar head fractures in adults and condylar fractures in children with mixed dentition is highly recommended, but this recommendation requires further investigations. (C) 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas

Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequency of these mutations in many subtypes of gliomas, and their association with clinical features of the patients, is poorly understood. Here we analyzed these loci in 363 brain tumors. ATRX is frequently mutated in grade II-III astrocytomas (71%), oligoastrocytomas (68%), and secondary glioblastomas (57%), and ATRX mutations are associated with IDH1 mutations and with an alternative lengthening of telomeres phenotype. CIC and FUBP1 mutations occurred frequently in oligodendrogliomas (46% and 24%, respectively) but rarely in astrocytomas or oligoastrocytomas (<10%). This analysis allowed us to define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and IDH1/CIC/FUBP1 (I-CF). Patients with I-CF gliomas had a significantly longer median overall survival (96 months) than patients with I-A gliomas (51 months) and patients with gliomas that did not harbor either signature (13 months). The genetic signatures distinguished clinically distinct groups of oligoastrocytoma patients, which usually present a diagnostic challenge, and were associated with differences in clinical outcome even among individual tumor types. In addition to providing new clues about the genetic alterations underlying gliomas, the results have immediate clinical implications, providing a tripartite genetic signature that can serve as a useful adjunct to conventional glioma classification that may aid in prognosis, treatment selection, and therapeutic trial design.

Comparison of the Clinical Expression of Patients with Ankylosing Spondylitis from Europe and Latin America

Objective. To compare the clinical, demographic, and serologic characteristics and the treatment of patients diagnosed with ankylosing spondylitis (AS) from Europe (EU) and Latin America (LA). Methods. We included 3439 patients from national registries: the Spanish Registry of Spondyloarthritis (REGISPONSER), the Belgian registry (ASPECT), and the Latin American Registry of Spondyloarthropathies (RESPONDIA). We selected patients with diagnosis of AS who met the modified New York classification criteria. Demographic, clinical, disease activity, functional, and metrological measurement data were recorded. Current treatment was recorded. The population was classified into 2 groups: patients with disease duration < 10 years and those with disease duration >= 10 years. A descriptive and comparative analysis of variables of both groups was carried out. Results. There were 2356 patients in EU group and 1083 in LA group. Prevalence of HLA-B27 was 71% in LA group and 83% in EU group (p < 0.001). We found a greater frequency of peripheral arthritis and enthesitis (p < 0.001) in the LA population; prevalence of arthritis was 57% in LA and 42% in EU, and for enthesitis, 54% and 38%. Except for treatment with anti-tumor necrosis factor (anti-TNF), the use of nonsteroidal antiinflammatory drugs (NSAID), corticosteroids, and disease-modifying antirheumatic drugs (DMARD), and the association of anti-TNF and methotrexate use showed a significant difference (p < 0.001) in the 2 populations. Conclusion. The principal differences in the clinical manifestations of patients with AS from EU and LA were the greater frequency of peripheral arthritis and enthesitis in LA group, the higher percentage of HLA-B27 in EU group, and the form of treatment, with a greater use of NSAID, steroids, and DMARD in the LA group. (First Release Nov 15 2012; J Rheumatol 2012;39:2315-20; doi:10.3899/jrheum.110687)

Use of passive diffusion sampling method for defining NO2 concentrations gradient in São Paulo, Brazil

Abstract Background Air pollution in São Paulo is constantly being measured by the State of Sao Paulo Environmental Agency, however there is no information on the variation between places with different traffic densities. This study was intended to identify a gradient of exposure to traffic-related air pollution within different areas in São Paulo to provide information for future epidemiological studies. Methods We measured NO2 using Palmes' diffusion tubes in 36 sites on streets chosen to be representative of different road types and traffic densities in São Paulo in two one-week periods (July and August 2000). In each study period, two tubes were installed in each site, and two additional tubes were installed in 10 control sites. Results Average NO2 concentrations were related to traffic density, observed on the spot, to number of vehicles counted, and to traffic density strata defined by the city Traffic Engineering Company (CET). Average NO2concentrations were 63μg/m3 and 49μg/m3 in the first and second periods, respectively. Dividing the sites by the observed traffic density, we found: heavy traffic (n = 17): 64μg/m3 (95% CI: 59μg/m3 – 68μg/m3); local traffic (n = 16): 48μg/m3 (95% CI: 44μg/m3 – 52μg/m3) (p < 0.001). Conclusion The differences in NO2 levels between heavy and local traffic sites are large enough to suggest the use of a more refined classification of exposure in epidemiological studies in the city. Number of vehicles counted, traffic density observed on the spot and traffic density strata defined by the CET might be used as a proxy for traffic exposure in São Paulo when more accurate measurements are not available.

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations. Conclusions This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.

Genome characterization through a mathematical model of the genetic code: an analysis of the whole chromosome 1 of A. thaliana

The objective of this work is to characterize the genome of the chromosome 1 of A.thaliana, a small flowering plants used as a model organism in studies of biology and genetics, on the basis of a recent mathematical model of the genetic code. I analyze and compare different portions of the genome: genes, exons, coding sequences (CDS), introns, long introns, intergenes, untranslated regions (UTR) and regulatory sequences. In order to accomplish the task, I transformed nucleotide sequences into binary sequences based on the definition of the three different dichotomic classes. The descriptive analysis of binary strings indicate the presence of regularities in each portion of the genome considered. In particular, there are remarkable differences between coding sequences (CDS and exons) and non-coding sequences, suggesting that the frame is important only for coding sequences and that dichotomic classes can be useful to recognize them. Then, I assessed the existence of short-range dependence between binary sequences computed on the basis of the different dichotomic classes. I used three different measures of dependence: the well-known chi-squared test and two indices derived from the concept of entropy i.e. Mutual Information (MI) and Sρ, a normalized version of the “Bhattacharya Hellinger Matusita distance”. The results show that there is a significant short-range dependence structure only for the coding sequences whose existence is a clue of an underlying error detection and correction mechanism. No doubt, further studies are needed in order to assess how the information carried by dichotomic classes could discriminate between coding and noncoding sequence and, therefore, contribute to unveil the role of the mathematical structure in error detection and correction mechanisms. Still, I have shown the potential of the approach presented for understanding the management of genetic information.

Enhanced proliferation and dopaminergic differentiation of ventral mesencephalic precursor cells by synergistic effect of FGF2 and reduced oxygen tension

Effective numerical expansion of dopaminergic precursors might overcome the limited availability of transplantable cells in replacement strategies for Parkinson's disease. Here we investigated the effect of fibroblast growth factor-2 (FGF2) and FGF8 on expansion and dopaminergic differentiation of rat embryonic ventral mesencephalic neuroblasts cultured at high (20%) and low (3%) oxygen tension. More cells incorporated bromodeoxyuridine in cultures expanded at low as compared to high oxygen tension, and after 6 days of differentiation there were significantly more neuronal cells in low than in high oxygen cultures. Low oxygen during FGF2-mediated expansion resulted also in a significant increase in tyrosine hydroxylase-immunoreactive (TH-ir) dopaminergic neurons as compared to high oxygen tension, but no corresponding effect was observed for dopamine release into the culture medium. However, switching FGF2-expanded cultures from low to high oxygen tension during the last two days of differentiation significantly enhanced dopamine release and intracellular dopamine levels as compared to all other treatment groups. In addition, the short-term exposure to high oxygen enhanced in situ assessed TH enzyme activity, which may explain the elevated dopamine levels. Our findings demonstrate that modulation of oxygen tension is a recognizable factor for in vitro expansion and dopaminergic differentiation of rat embryonic midbrain precursor cells.

Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Radiation exposure in whole-body computed tomography of multiple trauma patients: bearing devices and patient positioning

Whole-body computed tomography (WBCT) plays an important role in the management of severely injured patients. We evaluated the radiation exposure of WBCT scans using different positioning boards and arm positions.

Spine Ca2+ signaling in spike-timing-dependent plasticity

Calcium is a second messenger, which can trigger the modification of synaptic efficacy. We investigated the question of whether a differential rise in postsynaptic Ca2+ ([Ca2+]i) alone is sufficient to account for the induction of long-term potentiation (LTP) and long-term depression (LTD) of EPSPs in the basal dendrites of layer 2/3 pyramidal neurons of the somatosensory cortex. Volume-averaged [Ca2+]i transients were measured in spines of the basal dendritic arbor for spike-timing-dependent plasticity induction protocols. The rise in [Ca2+]i was uncorrelated to the direction of the change in synaptic efficacy, because several pairing protocols evoked similar spine [Ca2+]i transients but resulted in either LTP or LTD. The sequence dependence of near-coincident presynaptic and postsynaptic activity on the direction of changes in synaptic strength suggested that LTP and LTD were induced by two processes, which were controlled separately by postsynaptic [Ca2+]i levels. Activation of voltage-dependent Ca2+ channels before metabotropic glutamate receptors (mGluRs) resulted in the phospholipase C-dependent (PLC-dependent) synthesis of endocannabinoids, which acted as a retrograde messenger to induce LTD. LTP required a large [Ca2+]i transient evoked by NMDA receptor activation. Blocking mGluRs abolished the induction of LTD and uncovered the Ca2+-dependent induction of LTP. We conclude that the volume-averaged peak elevation of [Ca2+]i in spines of layer 2/3 pyramids determines the magnitude of long-term changes in synaptic efficacy. The direction of the change is controlled, however, via a mGluR-coupled signaling cascade. mGluRs act in conjunction with PLC as sequence-sensitive coincidence detectors when postsynaptic precede presynaptic action potentials to induce LTD. Thus presumably two different Ca2+ sensors in spines control the induction of spike-timing-dependent synaptic plasticity.