Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats

Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.Peer reviewe

Conformational and Structural Relaxations of Poly(ethylene oxide) and Poly(propylene oxide) Melts: Molecular Dynamics Study of Spatial Heterogeneity, Cooperativity, and Correlated Forward-Backward Motion

Performing molecular dynamics simulations for all-atom models, we characterize the conformational and structural relaxations of poly(ethylene oxide) and poly(propylene oxide) melts. The temperature dependence of these relaxation processes deviates from an Arrhenius law for both polymers. We demonstrate that mode-coupling theory captures some aspects of the glassy slowdown, but it does not enable a complete explanation of the dynamical behavior. When the temperature is decreased, spatially heterogeneous and cooperative translational dynamics are found to become more important for the structural relaxation. Moreover, the transitions between the conformational states cease to obey Poisson statistics. In particular, we show that, at sufficiently low temperatures, correlated forward-backward motion is an important aspect of the conformational relaxation, leading to strongly nonexponential distributions for the waiting times of the dihedrals in the various conformational statesComment: 13 pages, 13 figure

Organizing Engineering Work - A Comparative-Analysis

This article analyzes the organization of engineering work in six industrial capitalist countries. It identifies four major models for the organization of engineering work; the engineering profession did not succeed in achieving professional “closure” in any of the six countries under review. A review of the historical evolution of the organization of engineering work in each of the six countries reveals that engineering has been shaped by a complex interaction among the profession itself, employers, the state, labor, and preindustrial forces. However, none of the national variations on the four models for organizing engineering labor is stable or without internal contradiction because of the ambiguous “intermediate” position of engineers

Sources of variation in simulated ecosystem carbon storage capacity from the 5th Climate Model Intercomparison Project (CMIP5)

Ecosystem carbon (C) storage strongly regulates climate-C cycle feedback and is largely determined by both C residence time and C input from net primary productivity (NPP). However, spatial patterns of ecosystem C storage and its variation have not been well quantified in earth system models (ESMs), which is essential to predict future climate change and guide model development. We intended to evaluate spatial patterns of ecosystem C storage capacity simulated by ESMs as part of the 5th Climate Model Intercomparison Project (CMIP5) and explore the sources of multi-model variation from mean residence time (MRT) and/or C inputs. Five ESMs were evaluated, including C inputs (NPP and [gross primary productivity] GPP), outputs (autotrophic/heterotrophic respiration) and pools (vegetation, litter and soil C). ESMs reasonably simulated the NPP and NPP/GPP ratio compared with Moderate Resolution Imaging Spectroradiometer (MODIS) estimates except NorESM. However, all of the models significantly underestimated ecosystem MRT, resulting in underestimation of ecosystem C storage capacity. CCSM predicted the lowest ecosystem C storage capacity (~10 kg C m−2) with the lowest MRT values (14 yr), while MIROC-ESM estimated the highest ecosystem C storage capacity (~36 kg C m−2) with the longest MRT (44 yr). Ecosystem C storage capacity varied considerably among models, with larger variation at high latitudes and in Australia, mainly resulting from the differences in the MRTs across models. Our results indicate that additional research is needed to improve post-photosynthesis C-cycle modelling, especially at high latitudes, so that ecosystem C residence time and storage capacity can be appropriately simulated

A Manifesto Concerning the Legal Protection of Computer Programs

Rationale: There is conflicting evidence on whether patients with asthma experience an accelerated decline in lung function with age. We examined the association between postbronchodilator lung function, asthma, chronic rhinosinusitis (CRS), and atopy with age using a large European sample. Methods: In 17 centers in 11 European countries, case control studies were nested within representative cross-sectional surveys of adults aged less than 75 years. Representative samples of participants with asthma, CRS or both and controls were assessed for postbronchodilator ventilatory function, smoking history, atopy, and treatment. Multiple regression was used to assess the interactive effects of age and diagnostic group on decline in postbronchodilator ventilatory function. Results: A total of 3337 participants provided adequate data (778 with asthma, 399 with CRS, 244 with both asthma and CRS and 1916 controls who had neither asthma nor CRS). Participants with asthma had lower FEV1/FVC (-4.09% (95% CI: -5.02, -3.15, P < 0.001) and a steeper slope of FEV1/FVC against age (-0.14%/annum [95%CI: -0.19, -0.08]) equivalent to smoking 1-2 packs of cigarettes per day. Those with atopy had a slope equivalent to controls. Conclusions: People with asthma have a steeper decline in postbronchodilator lung function with age, but neither CRS nor atopy alone were associated with such decline

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial?

Background Low back pain (LBP) is common in the population and multifactorial in nature, often involving negative consequences. Reassuring information to improve coping is recommended for reducing the negative consequences of LBP. Adding a simple non-threatening explanation for the pain (temporary muscular dysfunction) has been successful at altering beliefs and behavior when delivered with other intervention elements. This study investigates the isolated effect of this specific information on future occupational behavior outcomes when delivered to the workforce. Design A cluster-randomized controlled trial. Methods Publically employed workers (n=505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non-threatening explanation for LBP - the ‘functional-disturbance’-model. Data collections took place monthly over a 1-year period using text message tracking (SMS). Primary outcomes were self-reported days of cutting down usual activities and work participation. Secondary outcomes were self-reported back beliefs, work ability, number of healthcare visits, bothersomeness, restricted activity, use of pain medication, and sadness/depression. Results There was no between-group difference in the development of LBP during follow-up. Cumulative logistic regression analyses showed no between-group difference on days of cutting down activities, but increased odds for more days of work participation in the intervention group (OR=1.83 95% CI: 1.08-3.12). Furthermore, the intervention group was more likely to report: higher work ability, reduced visits to healthcare professionals, lower bothersomeness, lower levels of sadness/depression, and positive back beliefs. Conclusion Reassuring information involving a simple non-threatening explanation for LBP significantly increased the odds for days of work participation and higher work ability among workers who went on to experience LBP during the 12-month follow-up. Our results confirm the potential for public-health education for LBP, and add to the discussion of simple versus multidisciplinary interventions