Environmental factors associated with autism spectrum disorder: a scoping review for the years 2003-2013. / Facteurs environnementaux associés au trouble du spectre de l'autisme : étude de délimitation portant sur les années 2003 à 2013.

INTRODUCTION: The number of children diagnosed with autism spectrum disorder (ASD) has been rapidly rising in the past decade. The etiology of this disorder, however, is largely unknown, although the environmental relative to the genetic contribution is substantial. We conducted a scoping review to comprehensively assess the current state of knowledge of the environmental factors present from preconception to early life associated with ASD, and to identify research gaps. METHODS: We searched electronic databases MEDLINE, PsycINFO and ERIC for articles on potential risk factors or protective factors from the physical and social environments associated with ASD and its subclassifications published between 1 January, 2003, and 12 July, 2013. We categorized articles into broad themes: chemical, physiological, nutritional and social factors, based on environmental exposure. RESULTS: We identified over 50 000 publications, but after ineligible studies were screened out, 315 articles remained. Most of these studies examined physiological factors, followed closely by chemical factors, and to a much lesser extent, nutritional and social factors, associated with ASD. Despite a vast literature and many heterogeneous studies, several risk factors emerged consistently: chemical factors such as traffic-related air pollutants; physiological factors including advanced parental age, preterm birth, low birth weight, hyperbilirubinemia and clustering of pregnancy complications; and maternal immigrant status. Despite extensive research on vaccines, findings overwhelmingly demonstrate no support for an association with ASD. CONCLUSION: The lack of consistency, temporality and specificity of associations between environmental factors and ASD remains the largest barrier to establishing causal relationships. More robust research is required to resolve inconsistencies in the literature. Future research should explore underlying mechanisms of associations between the risk factors that we identified and ASD.

INTRODUCTION: Le nombre d'enfants chez lesquels on diagnostique un trouble du spectre de l'autisme (TSA) grimpe rapidement depuis une décennie. L'étiologie de ce trouble est toutefois en grande partie inconnue, même si la contribution de l'environnement est importante par rapport à celle de la génétique. Nous avons procédé à une étude de délimitation pour évaluer en détail l'état actuel des connaissances sur les facteurs environnementaux présents depuis le stade de la préconception jusqu'au début de la vie que l'on associe au TSA et pour dégager les lacunes de la recherche. MÉTHODOLOGIE: Nous avons cherché dans les bases de données électroniques MEDLINE, PsycINFO et ERIC des articles portant sur des facteurs de risque potentiels ou des facteurs de protection des environnements physiques et sociaux associés au TSA et à ses sous-catégories entre le 1er janvier 2003 et le 12 juillet 2013. Nous avons regroupé les articles en thèmes généraux en fonction de l'exposition environnementale : facteurs chimiques, physiologiques, nutritionnels et sociaux. RÉSULTATS: Nous avons trouvé plus de 50 000 publications, mais après élimination des études inadmissibles il est resté 315 articles. La plupart de ces études portaient sur les facteurs psychologiques, suivis de près par les facteurs chimiques et, à un degré beaucoup moindre, les facteurs nutritionnels et sociaux associés au TSA. En dépit d'une masse importante de publications et de nombreuses études hétérogènes, quelques facteurs de risque se sont démarqués régulièrement : facteurs chimiques comme les polluants atmosphériques causés par la circulation; facteurs physiologiques, dont l'âge avancé des parents, les naissances prématurées, l'insuffisance de poids à la naissance, l'hyperbilirubinémie et les grappes de complications de la grossesse et enfin le statut de la mère vis-à-vis de l'immigration. En dépit de recherches poussées sur les vaccins, les faits révèlent de façon écrasante que rien n'appuie l'existence d'un lien avec le TSA. CONCLUSION: Le manque d'uniformité, de temporalité et de spécificité des liens entre les facteurs environnementaux et le TSA demeure l'obstacle le plus important dans l'établissement de liens de cause à effet. Une recherche plus robuste s'impose pour supprimer le manque d'uniformité dans les publications. Les recherches futures devraient porter sur des mécanismes sous-jacents des liens entre facteurs de risque que nous avons identifiés et le TSA.

Brain (Hyper)Excitability Revealed by Optimal Electrical Stimulation of GABAergic Interneurons.

BACKGROUND: Neurological disorders are often characterized by an excessive and prolonged imbalance between neural excitatory and inhibitory processes. An ubiquitous finding among these disorders is the disrupted function of inhibitory GABAergic interneurons. OBJECTIVE: The objective is to propose a novel stimulation procedure able to evaluate the efficacy of inhibition imposed by GABAergic interneurons onto pyramidal cells from evoked responses observed in local field potentials (LFPs). METHODS: Using a computational modeling approach combined with in vivo and in vitro electrophysiological recordings, we analyzed the impact of electrical extracellular, local, bipolar stimulation (ELBS) on brain tissue. We implemented the ELBS effects in a neuronal population model in which we can tune the excitation-inhibition ratio and we investigated stimulation-related parameters. Computer simulations led to sharp predictions regarding: i) the shape of evoked responses as observed in local field potentials, ii) the type of cells (pyramidal neurons and interneurons) contributing to these field responses and iii) the optimal tuning of stimulation parameters (intensity and frequency) to evoke meaningful responses. These predictions were tested in vivo (mouse). Neurobiological mechanisms were assessed in vitro (hippocampal slices). RESULTS: Appropriately-tuned ELBS allows for preferential activation of GABAergic interneurons. A quantitative neural network excitability index (NNEI) is proposed. It is computed from stimulation-induced responses as reflected in local field potentials. NNEI was used in four patients with focal epilepsy. Results show that it can readily reveal hyperexcitable brain regions. CONCLUSION: Well-tuned ELBS and NNEI can be used to locally probe brain regions and quantify the (hyper)excitability of the underlying brain tissue.

[Charcot's disease of the lumbosacral joint in spinal cord injury: a case report]. / Arthropathie neurogène de la charnière lombosacrée chez un paraplégique : à propos d'un cas.

OBJECTIVE: Comment on spinal damage in Charcot's disease. OBSERVATION: We report on a paraplegic patient with T9 spinal cord injury who developed destructive arthropathy of the lumbosacral joint. DISCUSSION: Charcot's disease occurs sporadically during the progression of certain chronic neurological diseases. It affects the limbs and the spine, where it causes major disc and vertebral damage. In cases of spinal cord injury, Charcot's disease must be considered when faced with the appearance of spinal deformity or the aggravation of neurological symptoms. Treatment of Charcot's disease requires spinal osteosynthesis for the relief of neurological compression and the re-establishment of spinal stability.

[Two key describers of the sacro-acetabular relationships: the angles of sacral and acetabular incidence]. / Deux descripteurs clé des relations sacro-cotyloïdiennes : les angles d'incidence sacrée et cotyloïde Mise en évidence par le logiciel De-Visu.

PURPOSE OF THE STUDY: Implantation of total hip arthroplasties raises several important questions concerning the relationship between the orientation of the lumbosacral joint and the acetabular-femoral joint; in other words, between the position of the patients trunk and the orientation of the acetabula. To elucidate better these complex relationships, we conducted a morphometry study on a sample of 51 dry pelves: pelv 26 female and 25 male specimens. MATERIAL AND METHODS: Three-dimensional coordinates of 47 homologous points were recorded for each pelvis. Data were then processed with De-Visu, a graphic visualization software. Seven parameters were compared: sacral slope, sacral incidence, and five parameters quantifying the three-dimensional orientation of the acetabula. RESULTS: The graphic modelization enabled an integral 3-D visualization of each pelvis. The sagittal view enabled simultaneous visualization of the sacrum, the sacroiliac joints, the acetabula, and their alignments, as well as the variability of their spatial relation. The position reference chosen to simulate the upright position aligned the anterior iliac spines and the superior pubic point. This position was found pertinent because the mean value of the sacral slope (41.8) and the sacral incidence (54) were not different from published series. The sacral slope was the most strongly correlated with the acetabular parameters. It exhibited a positive correlation with sagittal acetabular slope (r=0.59) and acetabular inclination (r=0.59). It exhibited a negative correlation with acetabular anteversion (R=0.45). The correlation with the sagittal acetabular slope was very strong for anteversion (r=0.92), and rose with acetabular inclination (r=-0.66). The angle formed by the two acetabular axes was highly variable (37). The correlation between this angle and inclination was very high in males (r=-0.88) and non-significant in females. There was however a very strong correlation with anteversion in females (r=-0.74) which was non-significant in males. This contrasting finding was related to the wide spread of the inclination values in males and anteversion values in females. DISCUSSION: We demonstrated a new sagittal parameter: the acetabular incidence. The summit of this angle is the center of the acetabulum. The sides are the pelvic thickness and the acetabular axes. This parameter was negatively correlated with the sacral incidence. It account simultaneously for the sagittal position of the sacrum in relation to the acetabula and for the degree of acetabular anteversion and inclination. We have demonstrated that the geometric sum of these two angles, sacral incidence and acetabular incidence, is equivalent to the sacro-acetabular angle demonstrated by Lazennec and Saillant. These authors showed that the sacro-acetabular angle is the sum of two positional parameters, the sacral slope and the sagittal acetabular tilt (or slope). The three angles -- sacral incidence, acetabular incidence, sacro-acetabular angle -- are anatomic angles which do not vary with the pelvic position.

Differences in osmotolerant and cell-wall properties of two Zygosaccharomyces rouxii strains.

The osmotolerant and cell wall properties of the two most studied wild-type Zygosaccharomyces rouxii strains (CBS 732 and ATCC 42981) were examined. Differences in their (1) tolerance to high salt content in the medium, (2) resistance to the lysing enzymes Lyticase and Zymolyase, (3) cell-wall polymer content and (4) cell wall micromorphology suggested that the less osmotolerant CBS 732 strain possesses a more rigid cell wall than the more osmotolerant ATCC 42981, whose cell wall seems to be more flexible and elastic.

[Asymptomatic blunt vertebral artery injury after cervical spine nonpenetrating trauma]. / Thrombose asymptomatique de l'artère vertébrale au cours des traumatismes fermés du rachis cervical.

OBJECTIVE: To show the possibility of vertebral injury after cervical spine trauma. METHOD: We observed 2 cases of asymptomatic thrombosis of the vertebral artery after cervical fracture. DISCUSSION: Thrombosis of the vertebral artery is acute in 20% of cases of cervical trauma. It may be asymptomatic. Magnetic resonance angiography is the best noninvasive investigation for such cases to systematically detect the complication. Treatment with anticoagulants or antiaggregants should be initiated.

CYGD: the Comprehensive Yeast Genome Database.

The Comprehensive Yeast Genome Database (CYGD) compiles a comprehensive data resource for information on the cellular functions of the yeast Saccharomyces cerevisiae and related species, chosen as the best understood model organism for eukaryotes. The database serves as a common resource generated by a European consortium, going beyond the provision of sequence information and functional annotations on individual genes and proteins. In addition, it provides information on the physical and functional interactions among proteins as well as other genetic elements. These cellular networks include metabolic and regulatory pathways, signal transduction and transport processes as well as co-regulated gene clusters. As more yeast genomes are published, their annotation becomes greatly facilitated using S.cerevisiae as a reference. CYGD provides a way of exploring related genomes with the aid of the S.cerevisiae genome as a backbone and SIMAP, the Similarity Matrix of Proteins. The comprehensive resource is available under http://mips.gsf.de/genre/proj/yeast/.

[Nonsurgical treatment of tennis elbow]. / Les traitements non chirurgicaux de la tendinopathie des épicondyliens.

OBJECTIVE: To review the literature on nonsurgical treatment of tennis elbow. METHODS: We searched Medline for all randomized controlled trials (RCTs), controlled clinical trials (CCTs) and literature reviews published from 1966 to December 2003 on nonsurgical treatment of tennis elbow. We used the keys words controlled clinical trial, tennis elbow on lateral epicondylitis, and treatment. We found 46 reports of RCTs and CCTs on 14 nonsurgical treatments and 11 literature reviews. RESULTS: Corticosteroid injection is the best treatment option for the short term. However, beneficial effects persisted only for a short time, and the long-term outcome could be poor. For the long term, physiotherapy (pulsed ultrasound, deep friction massage and exercise programme) was the best option but was not significantly different from the "wait-and-see" approach. Some support is offered for the use of topical nonsteroid anti-inflammatory drugs, at least for the short term. There is insufficient evidence to support or refute the use of acupuncture, extracorporeal shock wave therapy, manipulation, orthoses, low-energy laser, glycosaminoglycan polysulfate injection, botulinum toxin injection, or topical nitric oxide application. CONCLUSION: Further trials, with use of appropriate methods and adequate sample sizes, are needed before conclusions can be drawn about the effects of many of the treatments for tennis elbow and their ability to change the condition's natural course.

The sagittal anatomy of the sacrum among young adults, infants, and spondylolisthesis patients.

The anatomic pelvic parameter "incidence" - the angle between the line perpendicular to the middle of the sacral plate and the line joining the middle of the sacral plate to the center of the bicoxo-femoral axis - has been shown to be strongly correlated with the sacral slope and lumbar lordosis, and ensures the individual an economical standing position. It is important for determining the sagittal curve of the spine. The angle of incidence has also been shown to depend partly on the sagittal anatomy of sacrum, which is established in childhood while learning to stand and walk. The purpose of this study was (1) to define the relationship between the sacrum and the angle of incidence, and (2) to compare these parameters in three populations: young adults, infants before walking, and patients with spondylolisthesis. Forty-four normal young adults, 32 infants not yet walking and 39 patients with spondylolisthesis due to isthmic spondylolysis underwent a sagittal full-spine radiography. A graphic table and the software for bidimensional study of the sacrum developed by J. Hecquet were used to determine various anatomic and positional parameters. Comparison tests of means, and multiple and partial correlation tests were used. A study of the reliability of the measurements using factorial plan methods was performed. The sagittal anatomic parameters of the sacrum were found to have a close relationship with the pelvic parameter of incidence angle, and therefore with the sagittal balance of the spine. The anatomy of the sacrum in spondylolisthesis patients is particular in that some features are much like those of young infants, but it is more curved and the incidence angle is significantly larger. There is a close relationship between angle of incidence and the slip of spondylolisthesis. All the parameters of young infants are significantly smaller than those of adults. It can be concluded that the sagittal anatomy of the sacrum plays a key role in spinal sagittal balance. The sacral bone is an integral a part of the pelvis and constitutes the undistorted part of the spinal curves. Organization of sagittal curves during growth can be followed up by looking at the sacrum. The sacrum in the spondylolisthesis group differs from the normal, and the greater angle of incidence and sacral slope in this group could predispose to vertebral slip.

New plasmid system to select for Saccharomyces cerevisiae purine-cytosine permease affinity mutants.

The FCY2 gene of Saccharomyces cerevisiae encodes a purine-cytosine permease (PCP) that mediates the active transport of purines and cytosine. A structure-function model for this PCP has been recently proposed. In this study, we developed a plasmid-based system that generated a number of affinity-mutated alleles, enabling us to define new amino acids critical for permease function.

Involvement of very short DNA tandem repeats and the influence of the RAD52 gene on the occurrence of deletions in Saccharomyces cerevisiae.

Chromosomal rearrangements, such as deletions, duplications, or Ty transposition, are rare events. We devised a method to select for such events as Ura(+) revertants of a particular ura2 mutant. Among 133 Ura(+) revertants, 14 were identified as the result of a deletion in URA2. Of seven classes of deletions, six had very short regions of identity at their junctions (from 7 to 13 bp long). This strongly suggests a nonhomologous recombination mechanism for the formation of these deletions. The total Ura(+) reversion rate was increased 4.2-fold in a rad52Delta strain compared to the wild type, and the deletion rate was significantly increased. All the deletions selected in the rad52Delta context had microhomologies at their junctions. We propose two mechanisms to explain the occurrence of these deletions and discuss the role of microhomology stretches in the formation of fusion proteins.

Phylogenetic analyses indicate an atypical nurse-to-patient transmission of human immunodeficiency virus type 1.

A human immunodeficiency virus (HIV)-negative patient with no risk factor experienced HIV type 1 (HIV-1) primary infection 4 weeks after being hospitalized for surgery. Among the medical staff, only two night shift nurses were identified as HIV-1 seropositive. No exposure to blood was evidenced. To test the hypothesis of a possible nurse-to-patient transmission, phylogenetic analyses were conducted using two HIV-1 genomic regions (pol reverse transcriptase [RT] and env C2C4), each compared with reference strains and large local control sets (57 RT and 41 C2C4 local controls). Extensive analyses using multiple methodologies allowed us to test the robustness of phylogeny inference and to assess transmission hypotheses. Results allow us to unambiguously exclude one HIV-positive nurse and strongly suggest the other HIV-positive nurse as the source of infection of the patient.

Genomic exploration of the hemiascomycetous yeasts: 1. A set of yeast species for molecular evolution studies.

The identification of molecular evolutionary mechanisms in eukaryotes is approached by a comparative genomics study of a homogeneous group of species classified as Hemiascomycetes. This group includes Saccharomyces cerevisiae, the first eukaryotic genome entirely sequenced, back in 1996. A random sequencing analysis has been performed on 13 different species sharing a small genome size and a low frequency of introns. Detailed information is provided in the 20 following papers. Additional tables available on websites describe the ca. 20000 newly identified genes. This wealth of data, so far unique among eukaryotes, allowed us to examine the conservation of chromosome maps, to identify the 'yeast-specific' genes, and to review the distribution of gene families into functional classes. This project conducted by a network of seven French laboratories has been designated 'Génolevures'.

Genomic exploration of the hemiascomycetous yeasts: 3. Methods and strategies used for sequence analysis and annotation.

The primary analysis of the sequences for our Hemiascomycete random sequence tag (RST) project was performed using a combination of classical methods for sequence comparison and contig assembly, and of specifically written scripts and computer visualization routines. Comparisons were performed first against DNA and protein sequences from Saccharomyces cerevisiae, then against protein sequences from other completely sequenced organisms and, finally, against protein sequences from all other organisms. Blast alignments were individually inspected to help recognize genes within our random genomic sequences despite the fact that only parts of them were available. For each yeast species, validated alignments were used to infer the proper genetic code, to determine codon usage preferences and to calculate their degree of sequence divergence with S. cerevisiae. The quality of each genomic library was monitored from contig analysis of the DNA sequences. Annotated sequences were submitted to the EMBL database, and the general annotation tables produced served as a basis for our comparative description of the evolution, redundancy and function of the Hemiascomycete genomes described in other articles of this issue.

Genomic exploration of the hemiascomycetous yeasts: 4. The genome of Saccharomyces cerevisiae revisited.

Since its completion more than 4 years ago, the sequence of Saccharomyces cerevisiae has been extensively used and studied. The original sequence has received a few corrections, and the identification of genes has been completed, thanks in particular to transcriptome analyses and to specialized studies on introns, tRNA genes, transposons or multigene families. In order to undertake the extensive comparative sequence analysis of this program, we have entirely revisited the S. cerevisiae sequence using the same criteria for all 16 chromosomes and taking into account publicly available annotations for genes and elements that cannot be predicted. Comparison with the other yeast species of this program indicates the existence of 50 novel genes in segments previously considered as 'intergenic' and suggests extensions for 26 of the previously annotated genes.

Genomic exploration of the hemiascomycetous yeasts: 8. Zygosaccharomyces rouxii.

This paper reports the genomic analysis of strain CBS732 of Zygosaccharomyces rouxii, a homothallic diploid yeast. We explored the sequences of 4934 random sequencing tags of about 1 kb in size and compared them to the Saccharomyces cerevisiae gene products. Approximately 2250 nuclear genes, 57 tRNAs, the rDNA locus, the endogenous pSR1 plasmid and 15 mitochondrial genes were identified. According to 18S and 25S rRNA cladograms and to synteny analysis, Z. rouxii could be placed among the S. cerevisiae sensu lato yeasts.

Genomic exploration of the hemiascomycetous yeasts: 15. Pichia sorbitophila.

This paper reports the genomic analysis of the strain CBS7064 of Pichia sorbitophila, a homothallic diploid yeast. We sequenced 4829 random sequence tags of about 1 kb and compared them to the Saccharomyces cerevisiae gene products. Approximately 1300 nuclear genes, 22 tRNAs, the rDNA locus, and six mitochondrial genes have been identified. The analysis of the rDNA genes has permitted to classify this organism close to the Candida species. Accession numbers from AL414896 to AL419724 at EMBL databank.

Genomic exploration of the hemiascomycetous yeasts: 18. Comparative analysis of chromosome maps and synteny with Saccharomyces cerevisiae.

We have analyzed the evolution of chromosome maps of Hemiascomycetes by comparing gene order and orientation of the 13 yeast species partially sequenced in this program with the genome map of Saccharomyces cerevisiae. From the analysis of nearly 8000 situations in which two distinct genes having homologs in S. cerevisiae could be identified on the sequenced inserts of another yeast species, we have quantified the loss of synteny, the frequency of single gene deletion and the occurrence of gene inversion. Traces of ancestral duplications in the genome of S. cerevisiae could be identified from the comparison with the other species that do not entirely coincide with those identified from the comparison of S. cerevisiae with itself. From such duplications and from the correlation observed between gene inversion and loss of synteny, a model is proposed for the molecular evolution of Hemiascomycetes. This model, which can possibly be extended to other eukaryotes, is based on the reiteration of events of duplication of chromosome segments, creating transient merodiploids that are subsequently resolved by single gene deletion events.