Nitrosative stress, hypernitrosylation, and autoimmune responses to nitrosylated proteins: new pathways in neuroprogressive disorders Including depression and chronic fatigue syndrome.

Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function. However, in an environment of chronic oxidative and nitrosative stress (O&NS), nitrosylation of crucial cysteine groups within key enzymes of the thioredoxin, glutathione, and pyridoxine systems leads to their inactivation thereby disabling denitrosylation and transnitrosylation and subsequently a state described as "hypernitrosylation." This state leads to the development of pathology in multiple domains such as the inhibition of enzymes of the electron transport chain, decreased mitochondrial function, and altered conformation of proteins and amino acids leading to loss of immune tolerance and development of autoimmunity. Hypernitrosylation also leads to altered function or inactivation of proteins involved in the regulation of apoptosis, autophagy, proteomic degradation, transcription factor activity, immune-inflammatory pathways, energy production, and neural function and survival. Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis. In those disorders, increased bacterial translocation may drive hypernitrosylation and autoimmune responses against nitrosylated proteins.

Bending fatigue testing of commercial purity titanium for dental implants

High fatigue strength is one of the major requirements for dental implant materials. It was previously shown that the fatigue strength under conventional stress-control tension–compression testing can be doubled for commercially pure (CP) titanium processed by equal channel angular pressing. However, the fatigue endurance of an implant exposed to cyclic loading in corrosive media (bodily fluids) may potentially be compromised. In this work, non-conventional bending fatigue testing in air and in simulated body fluid (SBF) has been carried out for coarse-grained and ultrafine-grained CP titanium.

Clinical case report: yoga for fatigue in five young adult survivors of childhood cancer

PURPOSE: Cancer-related fatigue (CRF) is a distressing consequence of cancer and its treatment. CRF impacts many young adult (YA) survivors of childhood cancer, compromising work, social relationships, and daily activities. No satisfactory treatment exists. This pilot study aimed to assess the feasibility, safety, and preliminary efficacy of an 8-week twice/week Iyengar yoga (IY) intervention for treating persistent fatigue in YA survivors of childhood cancer. 

Prediction of non-proportional cyclic hardening and multiaxial fatigue life for FCC and BCC metals under constant amplitude of strain cycling

The fatigue lives are reduced accompanying an additional cyclic hardening under strain controlled non-proportional cyclic loading in which principal directions of stress and strain are altered within a cycle. This study predicts non-proportional cyclic hardening and multiaxial fatigue life for several BCC and FCC metals under constant amplitude strain cycling. A novel procedure to determine non-proportional cyclic hardening form uniaxial tensile properties has discussed in this study. Standard plastic strain energy density based fatigue criteria with considering the non-proportional cyclic hardening effect successfully predicts multiaxial fatigue lives. The predictions of non-proportional cyclic hardening and multiaxial fatigue life through models are validated by experimental results of various BCC and FCC metals which are collected from literatures.

Compassion fatigue and resilience: a qualitative analysis of social work practice

Compassion fatigue is a term used to describe behaviour and emotions experienced by those who help people who have experienced trauma. It is viewed as a potential consequence of stress related to such exposure and is understood to be influenced by the practitioner’s empathic response. The aims of this study were to obtain greater understanding of social workers experience of working with distressed clients; examine what develops personal, professional and organisational resilience; and explore ways in which workers can be better protected from compassion fatigue. The research design was qualitative using semi-structured interviews involving six social workers presently working with distressed clients or clients known to have experienced distress. Four major themes were identified using thematic analysis: (i) the complexities of social work, (ii) supportive and unsupportive contexts, (iii) promoting personal well-being/selfprotection and (iv) resilience as a changing systemic and complex process. The findings provide important insights into the participants’ experiences of working with distressed clients and, more specifically, their experience of compassion fatigue and stories of resilience. The research provides clear direction for future research at organisational, educational and interpersonal levels.

Effects of truck traffic on top-down fatigue cracking performance of flexible pavements using a new mechanics-based analysis framework

The mechanics-based analysis framework predicts top-down fatigue cracking initiation time in asphalt concrete pavements by utilising fracture mechanics and mixture morphology-based property. To reduce the level of complexity involved, traffic data were characterised and incorporated into the framework using the equivalent single axle load (ESAL) approach. There is a concern that this kind of simplistic traffic characterisation might result in erroneous performance predictions and pavement structural designs. This paper integrates axle load spectra and other traffic characterisation parameters into the mechanics-based analysis framework and studies the impact these traffic characterisation parameters have on predicted fatigue cracking performance. The traffic characterisation inputs studied are traffic growth rate, axle load spectra, lateral wheel wander and volume adjustment factors. For this purpose, a traffic integration approach which incorporates Monte Carlo simulation and representative traffic characterisation inputs was developed. The significance of these traffic characterisation parameters was established by evaluating a number of field pavement sections. It is evident from the results that all the traffic characterisation parameters except truck wheel wander have been observed to have significant influence on predicted top-down fatigue cracking performance.

Optical sensing of the fatigue damage state of CFRP under realistic aeronautical load sequences

Abstract: We present an optical sensing methodology to estimate the fatigue damage stateof structures made of carbon fiber reinforced polymer (CFRP), by measuring variations on the surface roughness. Variable amplitude loads (VAL), which represent realistic loads during aeronautical missions of fighter aircraft (FALSTAFF) have been applied to coupons until failure. Stiffness degradation and surface roughness variations have been measured during the life of the coupons obtaining a Pearson correlation of 0.75 between both variables. The data were compared with a previous study for Constant Amplitude Load (CAL) obtaining similar results. Conclusions suggest that the surface roughness measured in strategic zones is a useful technique for structural health monitoring of CFRP structures, and that it is independent of the type of load applied. Surface roughness can be measured in the field by optical techniques such as speckle, confocal perfilometers and interferometry, among others.

Surface irregularity factor as a parameter to evaluate the fatigue damage state of CFRP

This work presents an optical non-contact technique to evaluate the fatigue damage state of CFRP structures measuring the irregularity factor of the surface. This factor includes information about surface topology and can be measured easily on field, by techniques such as optical perfilometers. The surface irregularity factor has been correlated with stiffness degradation, which is a well-accepted parameter for the evaluation of the fatigue damage state of composite materials. Constant amplitude fatigue loads (CAL) and realistic variable amplitude loads (VAL), representative of real in- flight conditions, have been applied to “dog bone” shaped tensile specimens. It has been shown that the measurement of the surface irregularity parameters can be applied to evaluate the damage state of a structure, and that it is independent of the type of fatigue load that has caused the damage. As a result, this measurement technique is applicable for a wide range of inspections of composite material structures, from pressurized tanks with constant amplitude loads, to variable amplitude loaded aeronautical structures such as wings and empennages, up to automotive and other industrial applications.

Self-reported fatigue in children with advanced cancer: results of the PediQUEST study (TH309-A)

Background. Pediatric cancer-related fatigue, particularly self-reported, is poorly understood. Research Objectives. To describe fatigue and identify factors associated with it in the largest cohort of children with advanced cancer self-reporting symptoms to date.

Premature thermal fatigue failure of aluminium injection dies with duplex surface treatment

The premature failure of an aluminium injection die with a duplex surface treatment (plasma nitriding and physical vapor deposition coating) was investigated, in an effort to identify the causes of such premature failure of the component. The manufacturing and the operating conditions were documented. Analytical tools were used, including scanning electron microscopy with energy dispersive X-ray capability, X-ray diffraction, and instrumented microhardness testing. Preliminary observations showed a microstructure of coarse tempered martensite, and a considerably rough surface with porosity and cracks. A detailed analysis of crack initiation sites identified sulfur inclusions in the subsurface, underneath the coating. A further revision of the processing conditions revealed that a sulfur-impregnated grinding stone had been used to polish the die. The chemical composition of such grinding stone matched that of the inclusions found in the subsurface of the failed component. Thus, searched causes of premature failure could be discussed on the lights of the present findings.

Les facteurs psychosociaux reliés à la dysmorphie musculaire

Les hommes sont de plus en plus exposés à une pression sociale les incitant à présenter une silhouette mésomorphique, ce qui semble contribuer à les rendre plus insatisfaits de leur musculature. Cette insatisfaction peut mener au développement d’une dysmorphie musculaire (DM). Malgré que la DM soit classifiée comme un spécificateur du trouble de dysmorphie corporelle dans le DSM-V, plusieurs auteurs persistent à croire qu’il s’apparenterait davantage aux troubles des conduites alimentaires (TCA). La présente étude vise à approfondir les processus sous-jacents menant à la DM en appliquant le modèle socioculturel de Stice (1994), conçu pour les TCA, à la DM. Le modèle testé, adapté pour rendre compte des spécificités de la DM, propose que les influences socioculturelles mènent au désir d’être plus musclé, qui, lui, mène aux symptômes de la DM directement et indirectement par deux voies, la voie des affects négatifs et la voie comportementale. Trois cent quatre-vingt-six hommes ont été recrutés parmi les étudiants et employés de l’Université Laval et ont rempli des questionnaires en ligne. Le modèle a été testé à l’aide d’analyses acheminatoires. Bien que le modèle initial fasse preuve d’un bon ajustement, la voie des affects négatifs n’est un médiateur valide de la relation entre le désir d’être musclé et la DM que lorsque le lien entre le désir d’être plus musclé et les affects négatifs est modéré par le narcissisme vulnérable. Les résultats indiquent que l’internalisation du corps idéal influence le désir d’être plus musclé. Ce désir d’être plus musclé pousserait les hommes à développer des symptômes de la DM via deux processus, soit l’adoption de comportements visant à augmenter la musculature, et la présence d’affects négatifs, mais seulement chez des hommes présentant une vulnérabilité narcissique. Ceci fait ressortir la pertinence d’un modèle conçu pour les TCA afin d’expliquer les symptômes de la DM.

Augmentation de l’expression de la chaine α1 de la laminine 111, un potentiel traitement pour la Dystrophie musculaire de Duchenne

La protéine hétérotrimérique laminine-111 permet le lien entre la matrice-extracellulaire et l’intégrine α7β1 du sarcolemme, remplaçant ainsi dans les muscles dystrophiques, des liens normalement assurés par le complexe de la dystrophine. L’injection de laminine-111 dans des souris mdx a permis, entre autre, l’augmentation de l’expression de l’intégrine α7β1, d’empêcher les bris du sarcolemme lors de la contraction musculaire, de restaurer un niveau normal de la créatine kinase sérique, ainsi que d’augmenter la résistance et la force dans les muscles déficients en dystrophine. Ces résultats suggèrent que l’augmentation de la laminine-111 est un potentiel traitement pour la DMD. Les chaines β1 et γ1 de la laminine sont déjà exprimées dans le muscle humain adulte, mais la chaine α1 de la laminine (Lamα1) est exprimée uniquement pendant le stade très précoce 16 cellules de l’embryogenèse. Nous avons donc développé une méthode alternative à l’injection répétée de Laminine-111 en induisant l’expression endogène du gène LAMA1, afin de reformer le complexe trimérique α1β1γ1, la laminine 111. Ceci a été réalisé avec une technologie récente, le système CRISPR/Cas9, dont la Cas9 a été désactivée (dCas9) puis couplée à un domaine d’activation de la transcription, le VP160 (dCas9-VP160). L’utilisation d’un ou plusieurs ARN guides (ARNg) a permis de cibler le promoteur du gène LAMA1. L’ARNm de Lamα1 (qRT-PCR) ainsi que la protéine (immunohistochimie et immunobuvardage) n’ont pas été détecté dans le contrôle négatif, des myoblastes murins (C2C12). Cependant, une expression significative a été observée dans ces myoblastes transfectés avec des plasmides codant pour dCas9-VP160 et un ARNg. L’analyse protéique in vivo, dans des muscles de souris électroporés avec le même plasmide, a démontré une forte augmentation de la chaine α1 de la laminine. Des augmentations plus importantes de l’ARNm de Lamα1 ont été observées en utilisant 2 ARNg, suggérant un effet synergique. L’augmentation de l’expression de Lamα1 par le système de CRISPR/Cas9 devrait être étudiée d’avantage afin de vérifier si cette stratégie pourrait s’avérer efficace dans des cas de myopathies.