Профессиональные заболевания: классификация и способы предупреждения

Рассмотрены главные виды профессиональных заболеваний, их возникновение под действием различных причин. Приведены способы их профилактики, оценен ущерб от профессиональных заболеваний

A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition

The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH), 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10

Potent and Broad Neutralization of HIV-1 by a Llama Antibody Elicited by Immunization

Llamas (Lama glama) naturally produce heavy chain–only antibodies (Abs) in addition to conventional Abs. The variable regions (VHH) in these heavy chain–only Abs demonstrate comparable affinity and specificity for antigens to conventional immunoglobulins despite their much smaller size. To date, immunizations in humans and animal models have yielded only Abs with limited ability to neutralize HIV-1. In this study, a VHH phagemid library generated from a llama that was multiply immunized with recombinant trimeric HIV-1 envelope proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian-HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent from previous anti–HIV-1 VHH and its own germline sequence. J3 achieves broad and potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1 Env. This study may represent a new benchmark for immunogens to be included in B cell–based vaccines and supports the development of VHH as anti–HIV-1 microbicides

Cardiorespiratory fitness and activity explains the obesity-deprivation relationship in children

This study examined the association between obesity and deprivation in English children and whether cardiorespiratory fitness or physical activity (PA) can explain this association. Obesity was assessed using IOTF criteria in 8,398 10-16 year olds. Social deprivation was measured using the Index of Multiple Deprivation (IMD) (subdivided into 3 groups; high, mid and low deprivation). Obesity was analysed using binary logistic regression with stature, age and sex incorporated as confounding variables. Children's fitness levels were assessed using predicted VO2 max (20-metre shuttle run test) and PA was estimated using the PA Questionnaire for Adolescents or Children (PAQ). A strong association was found between obesity and deprivation. When fitness and PA were added to the logistic regression models, increasing levels in both were found to reduce the odds of obesity, although it was only by including fitness into the model that the association between obesity and deprivation disappeared. Including estimated PA into the model was found to be curvilinear. Initial increases in PA increase the odds of obesity. Only by increasing PA to exceed the 71(st) percentile (PAQ = 3.22) did the odds of being obese start to decline. In order to reduce deprivation inequalities in children's weight-status, health practitioners should focus on increasing cardiorespiratory fitness via physical activity levels in areas of greater deprivation

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1

Background: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. Methods: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs). Results: Two SNPs reached a level of genome-wide significance (P < 5 × 10−8) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10−8); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10−8). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (βmeta-analyis = 0.10, Pmeta-analyis = 9.3 × 10−10). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. Conclusions: In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases

NANO-IMPRINT TECHNOLOGY COMBINED WITH ROUGH TCO MORPHOLOGY AS DOUBLE TEXTURED LIGHT-TRAPPING SUPERSTRATE FOR THIN FILM SOLAR CELLS

Two types of nano-imprinted 2D grating textures were tested on their light trapping performance for thin film Si tandem solar cells in combination with various TCO’s. The combination with rough TCO layers like LPCVD ZnO leads to double textured superstrates that exhibit at least a similar light trapping capability as the state-of-the-art reference while using thinner TCO layers. Further optimization in combination with nano-imprinted AR textures on the air/glass interface has the potential for >13% devices with thin TCO and absorber layers

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data

Objective: To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Methods: Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M‐HAQ), the EuroQol 5‐domain (EQ‐5D; a quality‐of‐life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Results: Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM‐HAQ −0.047; P = 0.0100) and CDAI ≤2.8 (−0.073; P = 0.0003) but not DAS28‐CRP <2.6 (−0.022; P = 0.1735). Target attainment was associated with significantly improved EQ‐5D (0.022–0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline‐recommended disease targets were 36–45% less likely to be hospitalized (P < 0.0500) and 23–45% less likely to utilize DME (P < 0.0100). Conclusion: Attaining recommended target disease‐activity measures was associated with enhanced physical functioning and health‐related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the nociceptin/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (-/-) rats self-administer less cocaine (0.25, 0.125 or 0.5 mg/infusion) both under a Fixed Ratio 1 and a Progressive Ratio schedule of reinforcement compared to wild type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (-/-). When NOP (-/-) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showeda significantly lower drug intake compared to Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (-/-) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (-/-) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.Neuropsychopharmacology accepted article preview online, 26 August 2016. doi:10.1038/npp.2016.171

Trial outcomes and information for clinical decision-making: a comparative study of opinions of health professionals

Background: Trials are robust sources of data for clinical practice, however, trial outcomes may not reflect what is important to communicate for decision making. The study compared clinicians’ views of outcomes to include in a core outcome set for colorectal cancer (CRC) surgery, with what clinicians considered important information for clinical practice (core information). Methods: Potential outcomes/information domains were identified through systematic literature reviews, reviews of hospital information leaflets and interviews with patients. These were organized into 6 categories, and used to design a questionnaire survey that asked surgeons and nurses from a sample of CRC centers to rate the importance of each domain as an outcome or as information on a 9-point Likert scale. Respondents were re-surveyed (round 2) following group feedback (Delphi methods). Comparisons were made by calculating the difference in mean scores between the outcomes and information domains, and paired t-tests were used to explore the difference between mean scores of the 6 outcome/information categories. Results: Data sources identified 1216 outcomes/information of CRC surgery that informed a 94 item questionnaire. First round questionnaires were returned from 63/81 (78%) of centers. Clinicians rated 76/94 (84%) domains of higher importance to measure in trials than to information to communicate to patients in Round 1. This was reduced to 24/47 (51%) in Round 2. The greatest difference was evident in domains about survival, which was rated much more highly as a trial outcome than important piece of information for decision-making (mean difference 2.3, 95% CI 1.9-2.8, p<0.0001). Specific complications and quality-of-life domains were rated similarly (mean difference 0.18, 95% CI -0.1-0.4, p=0.2 and 0.2, 95% CI -0.1-0.5, p=0.2 respectively). Conclusions: Whilst clinicians want to measure key outcomes in trials, they rate these as less important to communicate in decision-making with patients. This discrepancy needs to be explored and addressed to maximize the impact of trials on clinical practice