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Background: The use of personal protective equipment (PPE) should be a culture of a workplace, and deeply rooted in worker behavior and attitude during their practice. According to the recent studies only 64% of the workers use PPE properly. The present study aims to investigate the utilization of PPE among workers in small and medium-sized enterprises (SMEs), and its relationship with knowledge, attitude, performance, and safety culture among workers., Methods: This cross-sectional study was carried out using a questionnaire tool across SMEs in Kashan city in year 2023. The used tool included three questionnaires: demographic, safety culture, and knowledge, attitude and performance. Study papulation was 529 SMEs. Totally, the sample size was 369 persons and questionnaires were distributed among the workers of SMEs. Finally, SPSS software was used for statistical analysis and structural equation modeling. Various statistical tests including T-Test, ANOVA, RMSEA, CFI, TLI, and the chi-square ratio were employed., Results: The mean values (standard deviation) of age and work experience were 35.19 (12.33), and 15.60 (1.69) years, respectively. Among the 369 participants, 267 participants (72.4%) indicated that they use some PPE, although not all types. However, 102 individuals (27.7%) do not employ any PPE. The lowest score for safety culture dimension was attributed to safety training at 1.58. The results of the final model indicate that the assumed relationships between variables, as outlined in the study objectives, were well established, with all connections proving statistically significant., Conclusion: It can be concluded that the missing of inadequate legal supervision for small industries exists. Therefore, it can be inferred that if supervision and regulation are enhanced for safety training and implementation that may lead to increased usage of PPE., (© 2024. The Author(s).)

Low-Salinity Water Flooding (LSWF) is a technique aimed at modifying the interactions between rock and fluids particularly altering wettability and reducing interfacial tension (IFT). However, there remains limited understanding of how heterogeneous wettability and the presence of Initial Water Saturation (S wi ) can impact the effectiveness of LSWF. This study contributes to a deeper understanding of LSWF mechanisms in the context of heterogeneous wettability, while also considering S wi . The simulations were conducted using OpenFOAM, employing a non-reactive quasi-three-phase flow solver that accounts for wettability alteration and IFT reduction during the mixing of Low-Salinity (LSW) and High-Salinity Water (HSW). A heterogeneous pore geometry is designed, and four distinct scenarios are simulated, encompassing both heterogeneous and homogeneous wettability conditions while considering the presence of S wi . These scenarios included secondary High-Salinity Water Flooding (HSWF), tertiary and secondary LSWF. Notably, the simulations reveal that secondary LSWF consistently yields the highest oil recovery across all scenarios, achieving recovery rates of up to 96.98 %. Furthermore, the presence of S wi significantly influences the performance of LSWF in terms of oil recovery, particularly in heterogeneous wettability conditions where it boosts recovery by up to 3.5 %, but in homogeneous wettability, it decreases recovery by nearly 26 %. These simulations also underscore the pivotal role played by the distribution of oil and HSW phases in profoundly affecting the outcomes of LSWF., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Protein properties and interactions have been widely investigated by using external labels. However, the micromolar sensitivity of the current dyes limits their applicability due to the high material consumption and assay cost. In response to this challenge, we synthesized a series of cyanine5 (Cy5) dye-based quencher molecules to develop an external dye technique to probe proteins at the nanomolar protein level in a high-throughput one-step assay format. Several families of Cy5 dye-based quenchers with ring and/or side-chain modifications were designed and synthesized by introducing organic small molecules or peptides. Our results showed that steric hindrance and electrostatic interactions are more important than hydrophobicity in the interaction between the luminescent negatively charged europium-chelate-labeled peptide (Eu-probe) and the quencher molecules. The presence of substituents on the quencher indolenine rings reduces their quenching property, whereas the increased positive charge on the indolenine side chain improved the interaction between the quenchers and the luminescent compound. The designed quencher structures entirely altered the dynamics of the Eu-probe (protein-probe) for studying protein stability and interactions, as we were able to reduce the quencher concentration 100-fold. Moreover, the new quencher molecules allowed us to conduct the experiments using neutral buffer conditions, known as the peptide-probe assay. These improvements enabled us to apply the method in a one-step format for nanomolar protein-ligand interaction and protein profiling studies instead of the previously developed two-step protocol. These improvements provide a faster and simpler method with lower material consumption.

Thermal shift assay (TSA) with altered temperature has been the most widely used method for monitoring protein stability for drug research. However, there is a pressing need for isothermal techniques as alternatives. This urgent demand arises from the limitations of TSA, which can sometimes provide misleading ranking of protein stability and fail to accurately reflect protein stability under physiological conditions. Although differential scanning fluorimetry has significantly improved throughput in comparison to differential scanning calorimetry and differential static light scattering throughput, all these methods exhibit moderate sensitivity. In contrast, current isothermal chemical denaturation (ICD) techniques may not offer the same throughput capabilities as TSA, but it provides more precise information about protein stability and interactions. Unfortunately, ICD also suffers from limited sensitivity, typically in micromolar range. We have developed a novel method to overcome these challenges, namely throughput and sensitivity. The novel Förster Resonance Energy Transfer (FRET)-Probe as an external probe is highly applicable to isothermal protein stability monitoring but also to conventional TSA. We have investigated ICD for multiple proteins with focus on KRAS G12C with covalent inhibitors and three chemical denaturants performed at nanomolar protein concentration. Data showed corresponding inhibitor-induced stabilization of KRAS G12C to those reported by nucleotide exchange assay., (© 2023. The Author(s).)

Objectives . This scientometric study aimed to investigate research and hot topics on unsafe behavior. Methods . The study was performed using scientometric analysis mapping tools, such as CiteSpace, Gephi, MINITAB and VOSviewer, for statistical analysis. Studies published in Web of Science were included. Results . The first study was published in 1987. The results of the study showed that the Safety Science journal with 111 studies (10.45%) presented most of the published studies in this field. The USA and China were the two highest producing countries, with 289 and 229 published studies, respectively. The results of keywords and hot topics showed that between 1991 and 2000 safety climate, safety performance and modeling were ranked as the first to third most frequent words, and during 2001-2010 safety performance was removed from the list of top 10 keywords while safety climate and modeling were ranked, respectively, ninth and sixth most frequent. Finally, between 2011 and 2020, the keyword of organizational factors rose to first rank, indicating the significance of this keyword in the future. Conclusions . According to the results of the present study, it can be concluded that future studies on unsafe behavior can be conducted in the field of organizational factors.

Background/aim: New luminometric chelates were developed for the detection of urinary bladder cancer and compared to cytology and urinary rapid tests BTA stat ® , NMP22 ® BladderChek ® and UBC ® Rapid Test., Materials and Methods: This single-center study analyzed urine from two different cohorts: Firstly, a retrospective pilot cohort (n=27) and secondly a prospective validation cohort (n=60) including patients with bladder cancer and healthy controls. The samples were studied with nine different terbium and europium chelates to detect cancer cases. After identification of an efficient luminophore in the first cohort, the second validation cohort was run with the selected chelates to re-evaluate the results and compare them with urinary rapid tests and cytology., Results: The compared methods showed area under the curve (AUC) values ranging from 0.567 to 0.767. Tb 3+ -chelate-based assay detected high-grade cancer cases (p=0.035) with an AUC of 0.663. The Eu-probe signal level was higher in cancer cases of any grade than in healthy controls (p=0.001) with an AUC of 0.759. The Eu-probe had a sensitivity of 46.7% and a specificity of 100% in cancer detection., Conclusion: Evaluation of terbium and europium chelates for the detection of urinary bladder cancer showed highest specificity among all methods and improved overall performance (characterized by AUC) compared to commercial urine-based rapid tests and cytology. The Eu-probe has the potential to be clinically valuable in urine-based detection of bladder cancer, especially for high-grade cancer., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A variety of studies have been conducted in Occupational diseases (ODs) and this makes it difficult for researchers to identify new areas of study. Therefore, the present study was conducted by examining Web of Science data to identify hot topics and research topics on ODs. This is a scientometric study performed using CiteSpace and Gephi software for statistical analysis. The published article in Web of Sciences was searched using the keywords "Occupational disease * " OR "Occupational illness * " OR "Industrial disease * " OR "Industrial illness * ". Finally, the countries and institutions and their cooperation, the most important and main topics discussed, and the path of future progress in ODs was analyzed. Preliminary results of the study show that out of 5,947 articles. The results of important journals showed that the American Journal of Industrial Medicine with 233 articles (6.02%), Oxford Occupational Medicine, and International Archives of Occupational and Environmental Health with 86 (2.22%), and 83 (2.15%), respectively. The two producing countries are the United States and Germany, which published 628 and 419 articles, respectively. The results of hot topics showed occupational exposures, epidemiology, mental health, and respiratory diseases were the most important keywords used in these 45 years. It can be concluded that Germany, with its current development trend in the coming years, will surpass the United States based on the number of articles and gain the first rank. Also, future studies can be conducted on respiratory diseases as the most important ODs and health care work as the most important job during the past years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saberi, Rabiei, Zare, Jazari and Malakoutikhah.)

Background: Surgeon's hands are exposed to a range of chemical and physical stressors that influence the integrity of gloves. Thus, glove perforation facilitates pathogen transmission through the holes. Numerous studies have shown that glove perforation is of great importance, but there is still no complete consensus., Objective: This study aimed to investigate the safety conditions of surgical gloves based on the incidence of glove perforation among surgical teams., Methods: A literature review was conducted by searching PubMed, Embase, Scopus, ISI, and ProQuest databases. The incidence of glove perforation was reviewed in eight categories. A total of 580 articles were found in the initial search., Results: 109 articles containing 130 datasets were analyzed. The overall incidence of glove perforation was 14.44 %. Surgeons had the highest incidence of glove perforation (23.09 %). An increase in the duration of surgery increased the odds of perforation. It was found that 68.58% of the glove perforations were not identified by practitioners., Conclusion: Despite major advances in the design of surgical gloves, the issue of safety and integrity of gloves has not improved. Due to the high incidence of surgical glove perforations, most of which had not been identified, it is imperative to consider strategies to minimize the incidence of perforation. The results of the present study can be used to integrate information related to the rate of perforation of surgical gloves in different surgeries.

Background: Some researchers state that they are not yet able to provide a deep understanding of the underlying causes of unsafe behaviors (UBs). Therefore, the present study was conducted to investigate the attitudes and experiences of Iranian workers of UBs., Methods: This present study was conducted in 35 industries using a semistructured interview based on grounded theory. Forty participants were interviewed, including 13 industrial safety and health experts and 27 workers and supervisors. The analysis of the present study consisted of a three-step coding process including open, axial, and selective coding., Results: The results showed that the factors affecting UBs could be classified into three categories: organizational, individual, and socioeconomic factors. Organizational factors were divided into 6 parts: procedure and environmental conditions, communications, monitoring, organizational safety culture, resource allocation, and human resources. Socioeconomic factors had three subcategories: community safety culture, type of organizational ownership, and economic problems. Finally, the individual factors were classified into two categories of personality traits and individual competence., Conclusion: The results showed that organizational factors were the most categorized, and it is estimated that this factor has a more important role in the UBs. Of course, to better understand the close relationship between these factors and find the weight and importance of each factor, it needs to measure it with multicriteria decision systems., Competing Interests: The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The Authors.)

Objective: Musculoskeletal disorders are one of the most important occupational problems especially among nurses. The aim of this study was to investigate the prevalence of musculoskeletal disorders in upper limbs and its associated psychosocial factors in the workplace., Methods: A systematic review was conducted by searching the Medline/PubMed, EMBASE, Scopus, ISI/web of knowledge and Google Scholar databases. The authors classified studies into categories of psychological work stressors and musculoskeletal problems. The statistical analysis was performed using Stata software., Results: We found 1742 articles in our initial search. After reviewing the titles, abstracts and full texts, 66 articles were finally analyzed. Psychosocial factors affecting the prevalence of upper limb musculoskeletal disorders among nurses were identified which included boring work, inadequate staffing, job demands, insufficient support, time pressure, decision latitude, job dissatisfaction, and job stress. There was a significant relationship between these factors and prevalence of musculoskeletal disorders in the wrists, shoulders, neck and shoulders, and wrists and hands., Conclusion: Collectively, the results of this study provide strong evidence of some psychosocial factors affecting the prevalence of upper limb musculoskeletal disorders among nurses. Thus, organizational interventions to minimize these stressors may be promising in reducing one risk factor for the development of nurses' musculoskeletal disorders. These interventions should not only consider the factors of physical ergonomics but also seek to improve the organizational aspects of the workplace.

Proteases are a group of enzymes with a catalytic function to hydrolyze peptide bonds of proteins. Proteases regulate the activity, signaling mechanism, fate, and localization of many proteins, and their dysregulation is associated with various pathological conditions. Proteases have been identified as biomarkers and potential therapeutic targets for multiple diseases, such as acquired immunodeficiency syndrome, cardiovascular diseases, osteoporosis, type 2 diabetes, and cancer, where they are essential to disease progression. Thus, protease inhibitors and inhibitor-like molecules are interesting drug candidates. To study proteases and their substrates and inhibitors, simple, rapid, and sensitive protease activity assays are needed. Existing fluorescence-based assays enable protease monitoring in a high-throughput compatible microtiter plate format, but the methods often rely on either molecular labeling or synthetic protease targets that only mimic the hydrolysis site of the true target proteins. Here, we present a homogenous, label-free, and time-resolved luminescence utilizing the protein-probe method to assay proteases with native and denatured substrates at nanomolar sensitivity. The developed protein-probe method is not restricted to any single protein or protein target class, enabling digestion and substrate fragmentation studies with the natural unmodified substrate proteins. The versatility of the assay for studying protease targets was shown by monitoring the digestion of a substrate panel with different proteases. These results indicate that the protein-probe method not only monitors the protease activity and inhibition, but also studies the substrate specificity of individual proteases.

Background: Musculoskeletal disorders are responsible for significant problem for workers' health. The present study aimed to investigate the prevalence of musculoskeletal disorders among mining workers., Methods: This systematic review and meta-analysis study were designed in 2020 (from Jan to Mar). The researchers searched five international databases Medline/PubMed, ProQuest, Scopus, Embase and Web of Science. All analyzes were performed using STATA statistical software., Results: The search results were 447 articles and after screening stage finally 50 studies were included in review. The highest number of studies (26 studies) reported the prevalence of musculoskeletal disorders of upper back and 4 studies reported the prevalence of musculoskeletal disorders of the arms and ankles & feet. The results of meta-analysis based on prevalence in different organs showed that the highest prevalence of musculoskeletal disorders was in the upper back and the lowest in the knees with a prevalence of 50.39% (CI 95%: 31.23-54.73%) and 16.03% (CI 95%: 11.78-20.28%), respectively., Conclusion: The prevalence of musculoskeletal disorders among miners is relatively high. Therefore, supervisors and mine managers should pay more attention to reducing musculoskeletal disorders and increasing the ergonomic level of mines in order to increase workers' health., Competing Interests: Conflict of interest Authors declare that there is no competing of interest., (Copyright © 2021 Rabiei et al. Published by Tehran University of Medical Sciences.)

Background: Occupational contact with blood and body fluids poses a significant risk to healthcare workers. The aim of this systematic review is to investigate the epidemiology and risk factors affecting needlestick injuries (NSI) in healthcare personnel in Iran., Methods: In March 2020, researchers studied six international databases such as Medline/PubMed, ProQuest, ISI/WOS, Scopus, Embase, and Google Scholar for English papers and two Iranian databases (MagIran and SID) for Persian papers. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess quality of studies. The method of reporting was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement., Results: A total of 43 articles were included in the analysis. Results showed that females (OR = 1.30, 95 % CI 1.06-1.58, P value = 0.009), younger age (OR = 2.75, 95 % CI 2.27-3.33, P value < 0.001, rotated shift workers (OR = 2.16, 95 % CI 1.47-3.15, P value < 0.001), not attending training courses (OR = 1.30, 95 % CI 1.07-1.56, P value = 0.006), working in the surgery ward (OR = 1.83, 95 % CI 1.33-2.50, P value < 0.001), less work experience (OR = 1.43, 95 % CI 1.04-1.95, P value = 0.025) apposed a greater risk factors for NSI among healthcare workers., Conclusion: Based on the results of this review, factors such as young age, less work experience, work shift, and female gender are considered as strong risk factors for NSI injury in Iran. Preventive measures including education programs can reduce the burden of NSI among healthcare personnel.

Objectives: The aim of this study was to model associated factors affecting musculoskeletal disorders (MSDs), using fuzzy logic in a steel factory in Iran., Methods: A cross-sectional study was conducted on steel industry workers. A 6-part questionnaire was used, consisting of demographic characteristics, occupational stress, work-family conflict, general health, occupational postures, and Nordic Musculoskeletal Questionnaire. Pearson correlation was used for statistical analysis., Results: The prevalence of MSDs for 270 participants in the studied factory was 94.8%. Job stress, work-family conflict, general health, and work posture had a statistically significant relationship with MSDs (P < .05). The fuzzy model demonstrated 23.8% predictability for the actual data of the study. The defuzzification data had significant correlation with real data of MSDs., Conclusions: The results of this study provided a new perspective about associated factors affecting MSDs and demonstrate that fuzzy logic can be used as a possible tool for evaluating MSDs., (Copyright © 2021. Published by Elsevier Inc.)

Background: Unsafe behaviors are the cause of 80% of accidents. However, there has also been no worldwide review and meta-analysis of the prevalence of workers' unsafe behaviors. Therefore, the present study aimed to investigate and estimate the prevalence of unsafe behaviors among Iranian workers using a systematic review and meta-analysis study., Methods: This systematic review and meta-analysis were conducted from Nov to Dec 2018. The researchers searched Medline/PubMed, Scopus, Embase, Science Direct, and Google Scholar for international articles and four Iranian databases (Scientific Information Database, MagIran, IranMedex, and IranDoc) for Persian articles. The method of reporting this study was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist., Results: Overall, 235 articles from databases were imported to EndNote library. Final screening of the included studies produced a total of 38 studies. Based on the random-effect model, the prevalence of total unsafe behaviors, nonuse or inappropriate use of personal protective equipment, and inappropriate work posture was 40.37% (CI 95% = 35.8-44.9), 27.79% (CI 95% = 21.2-34.3), and 14.87% (CI 95% = 10.7-18.9). There was no statistically significant relationship between unsafe behaviors and mean age, mean of work experiences, and year of study., Conclusion: The prevalence of unsafe behaviors among Iranian workers was relatively high and the most common behaviors were non-use or inappropriate use of PPE; one of the most important causes for this behavior is lack of training, inappropriate working conditions, and lack of positive attitude towards safety. Therefore, further studied are required to investigate the causes of these unsafe behaviors., Competing Interests: Conflicts of interest The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 Malakoutikhah et al. Published by Tehran University of Medical Sciences.)

Protein aggregation is a spontaneous process affected by multiple external and internal properties, such as buffer composition and storage temperature. Aggregation of protein-based drugs can endanger patient safety due, for example, to increased immunogenicity. Aggregation can also inactivate protein drugs and prevent target engagement, and thus regulatory requirements are strict regarding drug stability monitoring during manufacturing and storage. Many of the current technologies for aggregation monitoring are time- and material-consuming and require specific instruments and expertise. These types of assays are not only expensive, but also unsuitable for larger sample panels. Here we report a label-free time-resolved luminescence-based method using an external Eu 3+ -conjugated probe for the simple and fast detection of protein stability and aggregation. We focused on monitoring the properties of IgG, which is a common format for biological drugs. The Protein-Probe assay enables IgG aggregation detection with a simple single-well mix-and-measure assay performed at room temperature. Further information can be obtained in a thermal ramping, where IgG thermal stability is monitored. We showed that with the Protein-Probe, trastuzumab aggregation was detected already after 18 hours of storage at 60°C, 4 to 8 days earlier compared to SYPRO Orange- and UV250-based assays, respectively. The ultra-high sensitivity of less than 0.1% IgG aggregates enables the Protein-Probe to reduce assay time and material consumption compared to existing techniques.

The aggregation of Aβ peptide into amyloid fibrils in the brain is associated with Alzheimer's disease (AD). Inhibition of Aβ aggregation seemed a potential treatment for AD. It was previously shown that a short fragment of Aβ peptide (KLVFF, 16-20) bound Aβ inhibited its aggregation. In this work, using KLVFF peptide, we synthesized two peptide families and then evaluated their inhibitory capacities by conventional assays such as thioflavin T (ThT) fluorescence spectroscopy, turbidity measurement, and the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). The effect of peptide terminal groups on its inhibitory activity was first studied. Subsequently, the influence of halogenated amino acids on peptide anti-aggregation properties was investigated. We found that iodinated peptide with amine in the N and amide in the C termini, respectively, was the best inhibitor of Aβ fibers formation. Halogenated peptides seemed to decrease the number of Aβ fibrils; however, they did not reduce Aβ cytotoxicity. The data obtained in this work seemed promising in developing potential peptide drugs for treatment of AD., (© 2019 European Peptide Society and John Wiley & Sons, Ltd.)

Hepatocellular carcinoma or Liver cancer (LC) is the sixth most common cancer and the fourth cause of death worldwide in 2018. There has not been a comprehensive study on the survival rate of patients with LC in Asia yet. Therefore, the present study was conducted to evaluate the survival rate of patients with LC in Asian countries. The methodology of the present study is based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. The researchers searched five international databases including Medline/PubMed, Scopus, Embase, Web of Knowledge and ProQuest until July 1, 2018. We also searched Google Scholar for detecting grey literature. The Newcastle-Ottawa Quality Assessment Form was used to evaluate the quality of selected papers. A total of 1425 titles were retrieved. 63 studies met the inclusion criteria. Based on the random-effect model one-year, three-year and five-year survival rate of LC were 34.8 % (95 % CI; 30.3-39.3), 19 % (95 % CI ; 18.2-21.8) and 18.1 % (95 % CI ;16.1-20.1) respectively. According to the results of our study, the LC survival rate in Asian countries is relatively lower than in Europe and North America., (Copyright © 2020 Hassanipour et al.)

Background: Prostate cancer is one of the most common health issues among men, especially older men. In recent years, incidences of prostate cancer is increasing., Objective: The aim of this study was to provide a comprehensive estimate of the survival of prostate cancer in Asian countries., Methods: We searched five international databases including Medline/PubMed, Scopus, Embase, Web of Knowledge and ProQuest until June 1, 2018. The Newcastle-Ottawa Quality Assessment was used to evaluate the quality of selected papers. The review protocol was registered in PROSPERO (CRD42019117044)., Results: A total of 714 titles were retrieved. Thirty-seven studies met the inclusion criteria. Based on the random-effect model one-year, five-year and ten-year survival rate of prostate cancer were 81% (95% CI 77.8-84.2), 61.9% (95% CI 59.5-64.3) and 36.2% (95% CI 9.2-63.2) respectively. Survival rates based on HDI level for five-year were 30.07, 43.43 and 70.84 percent for medium, high and very high levels, respectively., Conclusion: According to the results of our study, the prostate cancer survival rate in Asian countries is relatively lower than in Europe and North America., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Background: Musculoskeletal disorders (MSDs) are considered an important health concern, particularly in automotive assembly industries. Evaluation of the effects of all MSDs risk factors is difficult due to its multifactorial nature. In addition, the risk factors cannot be detected accurately when they are only based on individual opinions. Thus, in this study, fuzzy logic tool was used to evaluate the combined effects of all risk factors on MSDs. Methods: This cross sectional study was conducted on 100 male workers in an automotive industry. Job satisfaction, job stress, job fatigue, and body posture were evaluated by a self-reported questionnaire. Body posture was evaluated using Rapid Entire Body Assessment (REBA). Primary data analysis on extracting the input variables of MATLAB was performed by SPSS 22, with a significant level of 0.05. T test, one-way Anova, and Pearson correlation analysis were used to extract the input variables for the fuzzy logic model. The results obtained from the Nordic questionnaire was selected as the output of the fuzzy model. Fuzzy logic assessment was performed using MATLAB software version 7.0. Results: There were significant differences between WMSDs factors, including job fatigue, strain, working posture, and the REBA final score, and pain in all limbs of the body (p<0.05). A significant difference was also found between working posture with wrist score (p<0.05). The findings on defuzzification showed a strong correlation between real and modelling results. Conclusion: The results showed that many factors such as posture, fatigue, and strain affect MSDs. Based on the obtained results, all categories of risk factors, including personal, psychosocial, and occupational, should be considered to predict MSDs, which can be achieved by a modeling approach., (© 2019 Iran University of Medical Sciences.)

An efficient approach for the synthesis of norbuprenorphin derivatives through coupling of enkephalins and norbuprenorphine intermediates is described. Norbuprenorphine derivative was synthesized from thebaine and then, its reaction with succinic acid and phthalic acid was also studied. Meanwhile, the synthesis of enkephalins was done using solid phase peptide synthesis approach. Furthermore, after cleavage of the peptide from the surface of the resin, the coupling of enkephalins with norbuprenorphine derivative was done using TBTU as a coupling reagent then the derivatives were purified using preparative high-pressure liquid chromatography and their structures were confirmed using high-resolution mass spectrometry data. Later, their permeability across membranes was investigated. After PAMPA studies, it was found that the permeability of all norbuprenorphin-enkephalin derivatives was increased; however, succinic and phthalic acid derivatives showed higher permeability than norbuprenorphine-Leu-enkephalin.

Background: Workforce health is one of the primary and most challenging issues, particularly in industrialized countries. This article aims at modeling the major factors affecting accidents in the workplace, including general health, work-family conflict, effort-reward imbalance, and internal and external locus of control., Methods: A cross-sectional study was conducted in Esfahan Steel Company in Iran. A total of 450 participants were divided into two groups-control and case-and the questionnaires were distributed among them. Data were collected through a 7-part questionnaire. Finally, the results were analyzed using SPSS 22.0 and Amos software., Results: All the studied variables had a significant relationship with the accident proneness. In the case group, general health with a coefficient of -0.37, work-family conflict with 0.10, effort-reward imbalance with 0.10, internal locus of control with -0.07, and external locus of control with 0.40 had a direct effect on occupational stress. Occupational stress also had a positive direct effect on accident proneness with a coefficient of 0.47. In addition, fitness indices of control group showed general health (-0.35), work-family conflict (0.36), effort-reward imbalance (0.13), internal locus of control (-0.15), and external locus of control (0.12) have a direct effect on occupational stress. Besides, occupational stress with a coefficient of 0.09 had a direct effect on accident proneness., Conclusion: It can be concluded that although previous studies and the present study showed the effect of stress on accident and accident proneness, some hidden and external factors such as work-family conflict, effort-reward imbalance, and external locus of control that affect stress should also be considered. It helps industries face less occupational stress and, consequently, less occurrence rates of accidents.

Background: Small and medium-sized enterprises (SMEs) include a large part of manufacturing jobs and play an important role in developing national economics and employment., Objectives: The present study aimed to investigate occupational health problems and safety conditions among SMEs in Shiraz, Iran., Methods: This cross-sectional study was carried out on 711 SMEs, including 371 small enterprises (fewer than 25 workers) and 340 medium enterprises (25-99 workers), in Shiraz, Iran. The participants were selected randomly among the workplaces under the coverage of social security insurance. The researcher-made questionnaire, which consisted of demographic characteristics, the frequency rate of occupational accidents, and exposure to workplace harmful agents, were distributed among participants., Findings: The results showed there were significantly more physical and chemical harmful agents in medium enterprises compared to small ones (P < 0.001). However, the frequency rate of accidents in small enterprises was significantly higher than in medium enterprises (P < 0.001). Also, there was no significant difference between the studied enterprises in ergonomic hazards, except for awkward posture, whose frequency rate was significantly higher in small enterprises (P < 0.05). Finally, among the reported symptoms, the prevalence of eye, skin, ear, and respiratory symptoms was significantly higher in medium enterprises compared to small enterprises (P < 0.05)., Conclusions: Occupational health and safety (OHS) regulations in medium enterprises have led to improved OHS conditions compared to small enterprises. Therefore, small enterprises should be included in OHS regulations., Competing Interests: The authors have no competing interests to declare., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.)

N-methylation is a powerful method to modify the physicochemical properties of peptides. We previously found that a fully N-methylated tetrapeptide, Ac-(N-MePhe) 4 -CONH 2 , was more lipophilic than its non-methylated analog Ac-(Phe) 4 -CONH 2 . In addition, the former crossed artificial and cell membranes while the latter did not. Here we sought to optimize the physicochemical properties of peptides and address how the number and position of N-methylated amino acids affect these properties. To this end, 15 analogs of Ac-(Phe) 4 -CONH 2 were designed and synthesized in solid-phase. The solubility of the peptides in water and their lipophilicity, as measured by ultra performance liquid chromatography (UPLC) retention times, were determined. To study the permeability of the peptides, the Parallel Artificial Membrane Permeability Assay (PAMPA) was used as an in vitro model of the blood-brain barrier (BBB). Contrary to the parent peptide, the 15 analogs crossed the artificial membrane, thereby showing that N-methylation improved permeability. We also found that N-methylation enhanced lipophilicity but decreased the water solubility of peptides. Our results showed that both the number and position of N-methylated residues are important factors governing the physicochemical properties of peptides. There was no correlation between the number of N-methylated amide bonds and any of the properties measured. However, for the peptides consecutively N-methylated from the N-terminus to the C-terminus (p1, p5, p11, p12 and p16), lipophilicity correlated well with the number of N-methylated amide bonds and the permeability of the peptides. Moreover, the peptides were non-toxic to HEK293T cells, as determined by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Directing self-assembly processes out-of-equilibrium to yield kinetically trapped materials with well-defined dimensions remains a considerable challenge. Kinetically controlled assembly of self-synthesizing peptide-functionalized macrocycles through a nucleation-growth mechanism is reported. Spontaneous fiber formation in this system is effectively shut down as most of the material is diverted into metastable non-assembling trimeric and tetrameric macrocycles. However, upon adding seeds to this mixture, well-defined fibers with controllable lengths and narrow polydispersities are obtained. This seeded growth strategy also allows access to supramolecular triblock copolymers. The resulting noncovalent assemblies can be further stabilized through covalent capture. Taken together, these results show that self-synthesizing materials, through their interplay between dynamic covalent bonds and noncovalent interactions, are uniquely suited for out-of-equilibrium self-assembly., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Drug delivery to the brain can be achieved by various means, including blood-brain barrier (BBB) disruption, neurosurgical-based approaches, and molecular design. Recently, passive diffusion BBB shuttles have been developed to transport low-molecular-weight drug candidates to the brain which would not be able to cross unaided. The low water solubility of these BBB shuttles has, however, prevented them from becoming a mainstream tool to deliver cargos across membranes. Here, we describe the design, synthesis, physicochemical characterization, and BBB-transport properties of phenylproline tetrapeptides, (PhPro)4, an improved class of BBB shuttles that operates via passive diffusion. These PhPro-based BBB shuttles showed 3 orders of magnitude improvement in water solubility compared to the gold-standard (N-MePhe)4, while retaining very high transport values. Transport capacity was confirmed when two therapeutically relevant cargos, nipecotic acid and l-3,4-dihydroxyphenylalanine (i.e., l-DOPA), were attached to the shuttle. Additionally, we used the unique chiral and conformationally restricted character of the (PhPro)4 shuttle to probe its chiral interactions with the lipid bilayer of the BBB. We studied the transport properties of 16 (PhPro)4 stereoisomers using the parallel artificial membrane permeability assay and looked at differences in secondary structure. Most stereoisomers displayed excellent transport values, yet this study also revealed pairs of enantiomers with high enantiomeric discrimination and different secondary structure, where one enantiomer maintained its high transport values while the other had significantly lower values, thereby confirming that stereochemistry plays a significant role in passive diffusion. This could open the door to the design of chiral and membrane-specific shuttles with potential applications in cell labeling and oncology.

Noninvasive methods for efficient drug delivery to the brain is an unmet need. Molecular access to the brain is regulated by the blood-brain barrier (BBB) established by the endothelial cells of brain vessels. Passive diffusion is one of the main mechanisms that organic compounds use to travel through these endothelial cells. This passage across the BBB is determined mainly by certain physicochemical properties of the molecule such as lipophilicity, size, and the presence of hydrogen bond donors and acceptors. One emerging strategy to facilitate the passage of organic compounds across the BBB is the use of peptide shuttles.1 In using this approach the permeability in front the BBB is, clearly, determined by the combined physicochemical properties of both the cargo and the shuttle. Herein we report the synthesis of a series of variations of one of the more efficient peptide shuttles, (N-MePhe)n . These include diverse structural features such as various backbone stereochemistries or the presence of non-natural amino acids, including halogenated residues. In several cases, we assessed the BBB permeability of both the shuttles alone and linked to a few cargos. Our results show how factors such as stereochemistry or halogen content influences the passage across the BBB and, more importantly, opens the way to a strategy of peptide shuttles 'à la carte', in which a particular fine-tuned shuttle is used for each specific cargo., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A family of self-replicating macrocycles was developed using dynamic combinatorial chemistry. Replication is driven by self-assembly of the replicators into fibrils and relies critically on mechanically induced fibril fragmentation. Analysis of separate dynamic combinatorial libraries made from one of six peptide-functionalized building blocks of different hydrophobicity revealed two selection criteria that govern the emergence of replicators from these systems. First, the replicators need to have a critical macrocycle size that endows them with sufficient multivalency to enable their self-assembly into fibrils. Second, efficient replication occurs only for library members that are of low abundance in the absence of a replication pathway. This work has led to spontaneous emergence of replicators with unrivalled structural complexity, being built from up to eight identical subunits and reaching a MW of up to 5.6 kDa. The insights obtained in this work provide valuable guidance that should facilitate future discovery of new complex self-replicating molecules. They may also assist in the development of new self-synthesizing materials, where self-assembly drives the synthesis of the very molecules that self-assemble. To illustrate the potential of this concept, the present system enables access to self-assembling materials made from self-synthesizing macrocycles with tunable ring size ranging from trimers to octamers.

Here we used solid-phase methods to prepare oligonucleotides carrying fibrin/ filaggrin citrullinated peptides. Post-synthetic conjugation protocols were successfully applied for the synthesis of oligonucleotides carrying small peptides. A stepwise protocol using acid treatment for the final deprotection allowed the preparation of polypyrimidine oligonucleotides carrying longer and arginine-rich peptides. An ELISA-based test using the oligonucleotide-citrullinated peptide conjugates was developed for the detection of anti-citrullinated protein/peptide antibodies in human serum from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.

Advances in the field of shuttle-mediated drug delivery have been made in the last decade; however, the treatment of brain disorders still remains a great challenge because of the presence of the blood-brain barrier (BBB), a structure that limits the access of drugs to their site of action in the central nervous system. Several strategies have been proposed to enhance the transport of drugs across the BBB. In this Review, we focus on the vector-mediated approach, in which a drug is coupled to a molecule (shuttle) that has the ability to cross the BBB and deliver the drug to the brain., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Here we studied the capacity of N-MePhe-(N-MePhe)(3)-CONH(2), Cha-(N-MePhe)(3)-CONH(2), and 2Nal-(N-MePhe)(3)-CONH(2) to carry various drugs (cargos) in in vitro blood-brain barrier (BBB) models in order to determine the versatility of these peptides as BBB-shuttles for drug delivery to the brain. Using SPPS, the peptides were coupled to GABA, Nip, and ALA to examine their passive BBB permeation by means of PAMPA and their lipophilicity by IAMC. Unaided, these nonpermeating drugs alone did not cross the PAMPA barrier and the BBB passively; however, the peptides tested as potential BBB shuttles transferred them by passive transfer through the PAMPA phospholipid. The permeability of peptides that showed the highest permeability in PAMPA, and Ac-N-MePhe-(N-MePhe)(3)-CONH(2) as the parent peptide was also examined in bovine brain microvessel endothelial cells (BBMECs). These peptide-based BBB shuttles open up the possibility to overcome the formidable obstacle of the BBB, thereby achieving drug delivery to the brain.

Several peptide families containing N-methylated amino acids were designed and synthesized using solid-phase peptide synthesis (SPPS). The permeability and phospholipophilicity of these compounds were studied by parallel artificial membrane permeability assay (PAMPA) and immobilized artificial membrane chromatography (IAMC) to select the best peptides in terms of length, terminal groups, and amino acid replacement to be used as carriers that pass through a model of the blood-brain barrier (BBB) by passive diffusion. Furthermore, the enzymatic stability of these peptides in human serum and their cell viability by MTT assay were tested. These peptide families showed great stability and nontoxicity. The three peptides that showed the greatest permeability were coupled to levodopa (a nonpassive permeating drug) and assessed. These peptides effectively transferred levodopa through an artificial membrane by means of passive diffusion.

Here we prepared and evaluated two libraries of mono-N-methylated and di-N-methylated diketopiperazines (DKPs) by parallel artificial membrane permeability assay and immobilized artificial membrane chromatography in order to obtain information on the features that govern the passage of peptidic molecules across the blood-brain barrier (BBB) by passive diffusion. On the basis of the results from these two libraries, we prepared and evaluated several DKP-baicalin and DKP-dopamine constructs. The DKPs or cyclic dipeptide scaffolds can be considered a novel family of brain delivery systems (BBB-shuttles) to transport to the brain drugs and other cargos that cannot cross the BBB unaided.