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

The genome of the seagrass Zostera marina reveals angiosperm adaptation to the sea

Seagrasses colonized the sea(1) on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet(2). Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes(3), genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae(4) and that is important for ion homoeostasis, nutrient uptake and O-2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming(5,6), to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants(7)

Estimating measures of interaction on an additive scale for preventive exposures

Measures of interaction on an additive scale (relative excess risk due to interaction [RERI], attributable proportion [AP], synergy index [S]), were developed for risk factors rather than preventive factors. It has been suggested that preventive factors should be recoded to risk factors before calculating these measures. We aimed to show that these measures are problematic with preventive factors prior to recoding, and to clarify the recoding method to be used to circumvent these problems. Recoding of preventive factors should be done such that the stratum with the lowest risk becomes the reference category when both factors are considered jointly (rather than one at a time). We used data from a case-control study on the interaction between ACE inhibitors and the ACE gene on incident diabetes. Use of ACE inhibitors was a preventive factor and DD ACE genotype was a risk factor. Before recoding, the RERI, AP and S showed inconsistent results (RERI = 0.26 [95%CI: −0.30; 0.82], AP = 0.30 [95%CI: −0.28; 0.88], S = 0.35 [95%CI: 0.02; 7.38]), with the first two measures suggesting positive interaction and the third negative interaction. After recoding the use of ACE inhibitors, they showed consistent results (RERI = −0.37 [95%CI: −1.23; 0.49], AP = −0.29 [95%CI: −0.98; 0.40], S = 0.43 [95%CI: 0.07; 2.60]), all indicating negative interaction. Preventive factors should not be used to calculate measures of interaction on an additive scale without recoding

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

BACKGROUND:Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS:Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE:MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured

Lower limb biomechanics during running in individuals with Achilles tendinopathy: a systematic review

<p>Abstract</p> <p>Background</p> <p>Abnormal lower limb biomechanics is speculated to be a risk factor for Achilles tendinopathy. This study systematically reviewed the existing literature to identify, critique and summarise lower limb biomechanical factors associated with Achilles tendinopathy.</p> <p>Methods</p> <p>We searched electronic bibliographic databases (Medline, EMBASE, Current contents, CINAHL and SPORTDiscus) in November 2010. All prospective cohort and case-control studies that evaluated biomechanical factors (temporospatial parameters, lower limb kinematics, dynamic plantar pressures, kinetics [ground reaction forces and joint moments] and muscle activity) associated with mid-portion Achilles tendinopathy were included. Quality of included studies was evaluated using the Quality Index. The magnitude of differences (effect sizes) between cases and controls was calculated using Cohen's d (with 95% CIs).</p> <p>Results</p> <p>Nine studies were identified; two were prospective and the remaining seven case-control study designs. The quality of 9 identified studies was varied, with Quality Index scores ranging from 4 to 15 out of 17. All studies analysed running biomechanics. Cases displayed increased eversion range of motion of the rearfoot (d = 0.92 and 0.67 in two studies), reduced maximum lower leg abduction (d = -1.16), reduced ankle joint dorsiflexion velocity (d = -0.62) and reduced knee flexion during gait (d = -0.90). Cases also demonstrated a number of differences in dynamic plantar pressures (primarily the distribution of the centre of force), ground reaction forces (large effects for timing variables) and also showed reduced peak tibial external rotation moment (d = -1.29). Cases also displayed differences in the timing and amplitude of a number of lower limb muscles but many differences were equivocal.</p> <p>Conclusions</p> <p>There are differences in lower limb biomechanics between those with and without Achilles tendinopathy that may have implications for the prevention and management of the condition. However, the findings need to be interpreted with caution due to the limited quality of a number of the included studies. Future well-designed prospective studies are required to confirm these findings.</p

Intrapopulation Variability Shaping Isotope Discrimination and Turnover: Experimental Evidence in Arctic Foxes

Tissue-specific stable isotope signatures can provide insights into the trophic ecology of consumers and their roles in food webs. Two parameters are central for making valid inferences based on stable isotopes, isotopic discrimination (difference in isotopic ratio between consumer and its diet) and turnover time (renewal process of molecules in a given tissue usually measured when half of the tissue composition has changed). We investigated simultaneously the effects of age, sex, and diet types on the variation of discrimination and half-life in nitrogen and carbon stable isotopes (δ15N and δ13C, respectively) in five tissues (blood cells, plasma, muscle, liver, nail, and hair) of a top predator, the arctic fox Vulpes lagopus. We fed 40 farmed foxes (equal numbers of adults and yearlings of both sexes) with diet capturing the range of resources used by their wild counterparts. We found that, for a single species, six tissues, and three diet types, the range of discrimination values can be almost as large as what is known at the scale of the whole mammalian or avian class. Discrimination varied depending on sex, age, tissue, and diet types, ranging from 0.3‰ to 5.3‰ (mean = 2.6‰) for δ15N and from 0.2‰ to 2.9‰ (mean = 0.9‰) for δ13C. We also found an impact of population structure on δ15N half-life in blood cells. Varying across individuals, δ15N half-life in plasma (6 to 10 days) was also shorter than for δ13C (14 to 22 days), though δ15N and δ13C half-lives are usually considered as equal. Overall, our multi-factorial experiment revealed that at least six levels of isotopic variations could co-occur in the same population. Our experimental analysis provides a framework for quantifying multiple sources of variation in isotopic discrimination and half-life that needs to be taken into account when designing and analysing ecological field studies

Conflict in the Indian Kashmir Valley II: psychosocial impact

ABSTRACT: BACKGROUND: India and Pakistan have disputed ownership of the Kashmir Valley region for many years, resulting in high level of exposure to violence among the civilian population of Kashmir (India). A survey was done as part of routine programme evaluation to assess confrontation with violence and its consequences on mental health, health service usage, and socio-economic functioning. METHODS: We undertook a two-stage cluster household survey in two districts of Kashmir (India) using questionnaires adapted from other conflict areas. Analysis was stratified for gender. RESULTS: Over one-third of respondents (n=510) were found to have symptoms of psychological distress (33.3%, CI: 28.3-38.4); women scored significantly higher (OR 2.5; CI: 1.7-3.6). A third of respondents had contemplated suicide (33.3%, CI: 28.3-38.4). Feelings of insecurity were associated with higher levels of psychological distress for both genders (males: OR 2.4, CI: 1.3-4.4; females: OR 1.9, CI: 1.1-3.3). Among males, violation of modesty, (OR 3.3, CI: 1.6-6.8), forced displacement, (OR 3.5, CI: 1.7-7.1), and physical disability resulting from violence (OR 2.7, CI: 1.2-5.9) were associated with greater levels of psychological distress; for women, risk factors for psychological distress included dependency on others for daily living (OR 2.4, CI: 1.3-4.8), the witnessing of killing (OR 1.9, CI: 1.1-3.4), and torture (OR 2.1, CI: 1.2-3.7). Self-rated poor health (male: OR 4.4, CI: 2.4-8.1; female: OR 3.4, CI: 2.0-5.8) and being unable to work (male: OR 6.7, CI: 3.5-13.0; female: OR 2.6, CI: 1.5-4.4) were associated with mental distress. CONCLUSIONS: The ongoing conflict exacts a huge toll on the communities' mental well-being. We found high levels of psychological distress that impacts on daily life and places a burden on the health system. Ongoing feelings of personal vulnerability (not feeling safe) were associated with high levels of psychological distress. Community mental health programmes should be considered as a way reduce the pressure on the health system and improve socio-economic functioning of those suffering from mental health problems

Cumulative occupational lumbar load and lumbar disc disease – results of a German multi-center case-control study (EPILIFT)

Background The to date evidence for a dose-response relationship between physical workload and the development of lumbar disc diseases is limited. We therefore investigated the possible etiologic relevance of cumulative occupational lumbar load to lumbar disc diseases in a multi-center case-control study. Methods In four study regions in Germany (Frankfurt/Main, Freiburg, Halle/Saale, Regensburg), patients seeking medical care for pain associated with clinically and radiologically verified lumbar disc herniation (286 males, 278 females) or symptomatic lumbar disc narrowing (145 males, 206 females) were prospectively recruited. Population control subjects (453 males and 448 females) were drawn from the regional population registers. Cases and control subjects were between 25 and 70 years of age. In a structured personal interview, a complete occupational history was elicited to identify subjects with certain minimum workloads. On the basis of job task-specific supplementary surveys performed by technical experts, the situational lumbar load represented by the compressive force at the lumbosacral disc was determined via biomechanical model calculations for any working situation with object handling and load-intensive postures during the total working life. For this analysis, all manual handling of objects of about 5 kilograms or more and postures with trunk inclination of 20 degrees or more are included in the calculation of cumulative lumbar load. Confounder selection was based on biologic plausibility and on the change-in-estimate criterion. Odds ratios (OR) and 95% confidence intervals (CI) were calculated separately for men and women using unconditional logistic regression analysis, adjusted for age, region, and unemployment as major life event (in males) or psychosocial strain at work (in females), respectively. To further elucidate the contribution of past physical workload to the development of lumbar disc diseases, we performed lag-time analyses. Results We found a positive dose-response relationship between cumulative occupational lumbar load and lumbar disc herniation as well as lumbar disc narrowing among men and women. Even past lumbar load seems to contribute to the risk of lumbar disc disease. Conclusions According to our study, cumulative physical workload is related to lumbar disc diseases among men and women