Исследование изменений твёрдости поверхности при азотировании сталей

Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques

Short Day–Mediated Cessation of Growth Requires the Downregulation of AINTEGUMENTALIKE1 Transcription Factor in Hybrid Aspen

Day length is a key environmental cue regulating the timing of major developmental transitions in plants. For example, in perennial plants such as the long-lived trees of the boreal forest, exposure to short days (SD) leads to the termination of meristem activity and bud set (referred to as growth cessation). The mechanism underlying SD–mediated induction of growth cessation is poorly understood. Here we show that the AIL1-AIL4 (AINTEGUMENTALIKE) transcription factors of the AP2 family are the downstream targets of the SD signal in the regulation of growth cessation response in hybrid aspen trees. AIL1 is expressed in the shoot apical meristem and leaf primordia, and exposure to SD signal downregulates AIL1 expression. Downregulation of AIL gene expression by SDs is altered in transgenic hybrid aspen plants that are defective in SD perception and/or response, e.g. PHYA or FT overexpressors. Importantly, SD–mediated regulation of growth cessation response is also affected by overexpression or downregulation of AIL gene expression. AIL1 protein can interact with the promoter of the key cell cycle genes, e.g. CYCD3.2, and downregulation of the expression of D-type cyclins after SD treatment is prevented by AIL1 overexpression. These data reveal that execution of SD–mediated growth cessation response requires the downregulation of AIL gene expression. Thus, while early acting components like PHYA and the CO/FT regulon are conserved in day-length regulation of flowering time and growth cessation between annual and perennial plants, signaling pathways downstream of SD perception diverge, with AIL transcription factors being novel targets of the CO/FT regulon connecting the perception of SD signal to the regulation of meristem activity

Long-term symptoms in dizzy patients examined in a university clinic

Background: The long-term course of dizziness was investigated combining medical chart and survey data. The survey was undertaken median (interquartile range (IQR)) 4.6 (4.3) years after the initial medical examination. Methods: Chart data comprised sex, age, diagnosis, symptom duration, postural sway and neck pain. Survey data comprised symptom severity assessed by the Vertigo Symptom Scale – Short Form (VSS-SF), and data regarding current state of dizziness, medication, neck pain and other chronic conditions. Results: The sample consisted of 503 patients, the mean (standard deviation (SD)) age was 50.0 (11.6) years, women being slightly overrepresented (60%). Severe problems with dizziness (VSS-SF mean (SD) 13.9, (10.8)) were indicated in the total group and in 5 of 6 diagnostic sub-groups. Vertigo/balance- and autonomic/anxiety-related symptoms were present in all groups. Current dizziness was confirmed by 73% who had significantly more severe problems than the non-dizzy (VSS-SF mean (SD): 17.2 (10.1) versus 5.0 (7.3)). Symptoms were related to vertigo/balance more than to autonomic/anxiety (test of interaction p < 0.001). Based on simple logistic regression analysis, sex, symptom duration, neck pain, sway and diagnoses predicted dizziness. Symptom duration and neck pain remained predictors in the adjusted analysis. Age, symptom duration, neck pain, sway and diagnoses predicted vertigo/balance-related dizziness in both regression analyses. Sex, neck pain and sway predicted development of autonomic/anxiety-related dizziness according to simple regression analysis, while only neck pain remained a significant predictor in the adjusted analysis. With respect to diagnosis, simple regression analysis showed significant reduced likelihood for development of dizziness in all vestibular sub-groups when compared to the non-otogenic dizziness group. With respect to vertigo/balance- and autonomic/anxiety-related symptoms, the implication of diagnostic belonging varied. No effect of diagnoses was seen in adjusted analyses. Conclusion: The majority of patients had persistent and severe problems with dizziness. The wait-and-see attitude before referral to specialist institutions may be questioned. Early, active movements seem necessary, and attention should be paid to the presence of neck pain. Diagnoses had limited prognostic value. Questionnaire-based evaluations could assist in classification and identification of type of dizziness and thereby provide a better basis for specific rehabilitation

CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection

Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200−/− mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R

Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR) compared with normal newborns (AGA). This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth.</p> <p>Methods</p> <p>Whole villous tissue was collected at birth from FGR (N = 20) and AGA neonates (N = 28). Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks), and principal component analysis and connectivity map.</p> <p>Results</p> <p>The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates.</p> <p>Conclusion</p> <p>These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.</p

Experimental neck muscle pain impairs standing balance in humans

Impaired postural control has been reported in patients with chronic neck pain of both traumatic and non-traumatic etiologies, but whether painful stimulation of neck muscle per se can affect balance control during quiet standing in humans remains unclear. The purpose of the present experiment was thus to investigate the effect of experimental neck muscle pain on standing balance in young healthy adults. To achieve this goal, 16 male university students were asked to stand upright as still as possible on a force platform with their eyes closed in two conditions of No pain and Pain of the neck muscles elicited by experimental painful electrical stimulation. Postural control and postural performance were assessed by the displacements of the center of foot pressure (CoP) and of the center of mass (CoM), respectively. The results showed increased CoP and CoM displacements variance, range, mean velocity, and mean and median frequencies in the Pain relative to the No pain condition. The present findings emphasize the destabilizing effect of experimental neck muscle pain per se, and more largely stress the importance of intact neck neuromuscular function on standing balance

Manual therapy with and without vestibular rehabilitation for cervicogenic dizziness: a systematic review

<p>Abstract</p> <p>Background</p> <p>Manual therapy is an intervention commonly advocated in the management of dizziness of a suspected cervical origin. Vestibular rehabilitation exercises have been shown to be effective in the treatment of unilateral peripheral vestibular disorders, and have also been suggested in the literature as an adjunct in the treatment of cervicogenic dizziness. The purpose of this systematic review is to evaluate the evidence for manual therapy, in conjunction with or without vestibular rehabilitation, in the management of cervicogenic dizziness.</p> <p>Methods</p> <p>A comprehensive search was conducted in the databases Scopus, Mantis, CINHAL and the Cochrane Library for terms related to manual therapy, vestibular rehabilitation and cervicogenic dizziness. Included studies were assessed using the Maastricht-Amsterdam criteria.</p> <p>Results</p> <p>A total of fifteen articles reporting findings from thirteen unique investigations, including five randomised controlled trials and eight prospective, non-controlled cohort studies were included in this review. The methodological quality of the included studies was generally poor to moderate. All but one study reported improvement in dizziness following either unimodal or multimodal manual therapy interventions. Some studies reported improvements in postural stability, joint positioning, range of motion, muscle tenderness, neck pain and vertebrobasilar artery blood flow velocity.</p> <p>Discussion</p> <p>Although it has been argued that manual therapy combined with vestibular rehabilitation may be superior in the treatment of cervicogenic dizziness, there are currently no observational and experimental studies demonstrating such effects. A rationale for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is presented.</p> <p>Conclusion</p> <p>There is moderate evidence to support the use of manual therapy, in particular spinal mobilisation and manipulation, for cervicogenic dizziness. The evidence for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is lacking. Further research to elucidate potential synergistic effects of manual therapy and vestibular rehabilitation is strongly recommended.</p

Crystal Structures of the ATPase Domains of Four Human Hsp70 Isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78

The 70-kDa heat shock proteins (Hsp70) are chaperones with central roles in processes that involve polypeptide remodeling events. Hsp70 proteins consist of two major functional domains: an N-terminal nucleotide binding domain (NBD) with ATPase activity, and a C-terminal substrate binding domain (SBD). We present the first crystal structures of four human Hsp70 isoforms, those of the NBDs of HSPA1L, HSPA2, HSPA5 and HSPA6. As previously with Hsp70 family members, all four proteins crystallized in a closed cleft conformation, although a slight cleft opening through rotation of subdomain IIB was observed for the HSPA5-ADP complex. The structures presented here support the view that the NBDs of human Hsp70 function by conserved mechanisms and contribute little to isoform specificity, which instead is brought about by the SBDs and by accessory proteins.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1