Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Is tension band wiring technique the "gold standard" for the treatment of olecranon fractures? A long term functional outcome study

<p>Abstract</p> <p>Background</p> <p>Tension band wiring (TBW) remains the most common operative technique for the internal fixation of olecranon fractures despite the potential occurrence of subjective complaints due to subcutaneous position of the hardware. Aim of this long term retrospective study was to evaluate the elbow function and the patient-rated outcome after TBW fixation of olecranon fractures.</p> <p>Methods</p> <p>We reviewed 62 patients (33 men and 29 women) with an average age of 48.6 years (range, 18–85 years) who underwent TBW osteosynthesis for isolated olecranon fractures. All patients were assessed both clinically with measurement of flexion-extension and pronation-supination arcs and radiologically with elbow X-Rays. Functional outcome was estimated using the Mayo Elbow Performance Score (MEPS), Visual Analogue Scale (VAS) subjective pain score and VAS patient satisfaction score. Follow up: 6–13 years (average 8.2 years).</p> <p>Results</p> <p>There was a higher prevalence of fractures among men until the 5th decade of life and among women in elderly (p = 0.032). Slip or simple fall onto the arm was the main mechanism of injury for 38 fractures (61.3%) while high energy trauma, such as fall from a height (> 2 m) or road accident, was reported in 24 fractures (38.7%). Hardware removal performed in 51 patients (82.3%) but 34 of them (66.6% of removals) were still complaining for mild pain during daily activities. The incidence of pin migration and loosening was not statistically decreased when penetration of the anterior ulnar cortex was accomplished (p = 0.304). Supination was more often affected than pronation (p = 0.027). According to MEPS, 53 patients (85.5%) had a good to excellent result, 6 (9.7%) fair and 3 (4.8%) poor result. The average satisfaction rating was 9.3 out of 10 (range, 6–10) with 31 patients (50%) to remain completely satisfied from the final result. Degenerative changes recorded in 30 elbows (48.4%). However, no correlation could be found between radiographic findings and MEPS (p = 0.073).</p> <p>Conclusion</p> <p>Tension band wiring fixation remains the "gold standard" for the treatment of displaced and minimally comminuted olecranon fractures. In long term, low levels of pain may be evident regardless of whether the metalware is removed and degenerative changes have been developed.</p

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer

International audienceIntroduction: Breast cancers are traditionally divided into hormone-receptor positive and negative cases. This classification helps to guide patient management. However, a subgroup of hormone-receptor positive patients relapse irrespective of hormonal therapy. Gene expression profiling has classified breast tumours into five major subtypes with significant different outcome. The two luminal subtypes, A and B, show high expression of ESR1, GATA3 and FOXA1 genes. Prognostic biomarkers for oestrogen receptor (ER)-positive cases include progesterone receptor (PR) and androgen receptor (AR), and proteins related to proliferation or apoptotic resistance. The aim of this study was to identify the best predictors of success of hormonal therapy.Methods: By immunohistochemistry we studied 10 markers in a consecutive series of 832 cases of breast carcinoma treated at the Paoli-Calmettes Institute from 1990 to 2002 and deposited onto tissue microarrays (TMA). These markers were luminal-related markers ER, PR, AR, FOXA1 and GATA3 transcription factors, proliferation-related Ki67 and CCND1, ERBB2, anti-apoptotic BCL2 and P53. We also measured vascular peritumoural invasion (VPI), size, grade and lymph node involvement. For 143 cases, gene expression profiles were available. Adjuvant chemotherapy and hormonal therapy were given to high- and low-risk patients, respectively. The 162 events observed and taken into account were metastases.Results: Molecular expression of the 10 parameters and subtype with ER status were strongly correlated. Of the 67 luminal A cases of this series, 63 were ER-positive. Multivariate analyses showed the highly significant prognostic value of VPI (hazard ratio (HR) = 2.47), Ki67 (HR = 2.9), P53 (HR = 2.9) and GATA3 (HR = 0.5) for the 240 patients who received hormonal therapy.Conclusions: A panel of three antibodies (Ki67, P53 and GATA3) associated with VPI can significantly improve the traditional prognosticators in predicting outcome for ER-positive breast cancer patients receiving hormonal therapy

Biosynthesis of Unusual Moth Pheromone Components Involves Two Different Pathways in the Navel Orangeworm, Amyelois transitella

The sex pheromone of the navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), consists of two different types of components, one type including (11Z,13Z)-11,13-hexadecadienal (11Z,13Z-16:Ald) with a terminal functional group containing oxygen, similar to the majority of moth pheromones reported, and another type including the unusual long-chain pentaenes, (3Z,6Z,9Z,12Z,15Z)-3,6,9,12,15-tricosapentaene (3Z,6Z,9Z,12Z,15Z-23:H) and (3Z,6Z,9Z,12Z,15Z)- 3,6,9,12,15-pentacosapentaene (3Z,6Z,9Z,12Z,15Z-25:H). After decapitation of females, the titer of 11Z,13Z-16:Ald in the pheromone gland decreased significantly, whereas the titer of the pentaenes remained unchanged. Injection of a pheromone biosynthesis activating peptide (PBAN) into the abdomens of decapitated females restored the titer of 11Z,13Z-16:Ald and even increased it above that in intact females, whereas the titer of the pentaenes in the pheromone gland was not affected by PBAN injection. In addition to common fatty acids, two likely precursors of 11Z,13Z-16:Ald, i.e., (Z)-11-hexadecenoic and (11Z,13Z)-11,13-hexadecadienoic acid, as well as traces of (Z)-6-hexadecenoic acid, were found in gland extracts. In addition, pheromone gland lipids contained (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoic acid, which also was found in extracts of the rest of the abdomen. Deuterium-labeled fatty acids, (16,16,16-D3)-hexadecanoic acid and (Z)-[13,13,14,14,15,15,16,16,16-D9]-11-hexadecenoic acid, were incorporated into 11Z,13Z-16:Ald after topical application to the sex pheromone gland coupled with abdominal injection of PBAN. Deuterium label was incorporated into the C23 and C25 pentaenes after injection of (9Z,12Z,15Z)- [17,17,18,18,18-D5]-9,12,15-octadecatrienoic acid into 1–2 d old female pupae. These labeling results, in conjunction with the composition of fatty acid intermediates found in pheromone gland extracts, support different pathways leading to the two pheromone components. 11Z,13Z-16:Ald is probably produced in the pheromone gland by Δ11 desaturation of palmitic acid to 11Z-16:Acid followed by a second desaturation to form 11Z,13Z-16:Acid and subsequent reduction and oxidation. The production of 3Z,6Z,9Z,12Z,15Z-23:H and 3Z,6Z,9Z,12Z,15Z-25:H may take place outside the pheromone gland, and appears to start from linolenic acid, which is elongated and desaturated to form (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoic acid, followed by two or three further elongation steps and finally reductive decarboxylation

The effect of forearm posture on wrist flexion in computer workers with chronic upper extremity musculoskeletal disorders

<p>Abstract</p> <p>Background</p> <p>Occupational computer use has been associated with upper extremity musculoskeletal disorders (UEMSDs), but the etiology and pathophysiology of some of these disorders are poorly understood. Various theories attribute the symptoms to biomechanical and/or psychosocial stressors. The results of several clinical studies suggest that elevated antagonist muscle tension may be a biomechanical stress factor. Affected computer users often exhibit limited wrist range of motion, particularly wrist flexion, which has been attributed to increased extensor muscle tension, rather than to pain symptoms. Recreational or domestic activities requiring extremes of wrist flexion may produce injurious stress on the wrist joint and muscles, the symptoms of which are then exacerbated by computer use. As these activities may involve a variety of forearm postures, we examined whether changes in forearm posture have an effect on pain reports during wrist flexion, or whether pain would have a limiting effect on flexion angle.</p> <p>Methods</p> <p>We measured maximum active wrist flexion using a goniometer with the forearm supported in the prone, neutral, and supine postures. Data was obtained from 5 subjects with UEMSDs attributed to computer use and from 13 control subjects.</p> <p>Results</p> <p>The UEMSD group exhibited significantly restricted wrist flexion compared to the control group in both wrists at all forearm postures with the exception of the non-dominant wrist with the forearm prone. In both groups, maximum active wrist flexion decreased at the supine forearm posture compared to the prone posture. No UEMSD subjects reported an increase in pain symptoms during testing.</p> <p>Conclusion</p> <p>The UEMSD group exhibited reduced wrist flexion compared to controls that did not appear to be pain related. A supine forearm posture reduced wrist flexion in both groups, but the reduction was approximately 100% greater in the UEMSD group. The effect of a supine forearm posture on wrist flexion is consistent with known biomechanical changes in the distal extensor carpi ulnaris tendon that occur with forearm supination. We infer from these results that wrist extensor muscle passive tension may be elevated in UEMSD subjects compared to controls, particularly in the extensor carpi ulnaris muscle. Measuring wrist flexion at the supine forearm posture may highlight flexion restrictions that are not otherwise apparent.</p

Interpreting outcome following foot surgery in people with rheumatoid arthritis

BACKGROUND: Foot surgery is common in RA but the current lack of understanding of how patients interpret outcomes inhibits evaluation of procedures in clinical and research settings. This study aimed to explore which factors are important to people with RA when they evaluate the outcome of foot and ankle surgery. METHODS AND RESULTS: Semi structured interviews with 11 RA participants who had mixed experiences of foot surgery were conducted and analysed using thematic analysis. Responses showed that while participants interpreted surgical outcome in respect to a multitude of factors, five major themes emerged: functional ability, participation, appearance of feet and footwear, surgeons' opinion, and pain. Participants interpreted levels of physical function in light of other aspects of their disease, reflecting on relative change from their preoperative state more than absolute levels of ability. Appearance was important to almost all participants: physical appearance, foot shape, and footwear were closely interlinked, yet participants saw these as distinct concepts and frequently entered into a defensive repertoire, feeling the need to justify that their perception of outcome was not about cosmesis. Surgeons' post-operative evaluation of the procedure was highly influential and made a lasting impression, irrespective of how the outcome compared to the participants' initial goals. Whilst pain was important to almost all participants, it had the greatest impact upon them when it interfered with their ability to undertake valued activities. CONCLUSIONS: People with RA interpret the outcome of foot surgery using multiple interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than anticipated. These factors can help clinicians in discussing surgical options in patients