Publications by authors named "Vladimír Bencko"

139 Publications

Principles of evidence-based medicine: from Robert Kochs postulates to a current EBM concept.

Authors:
Vladimír Bencko

Cas Lek Cesk 2021 ;160(2-3):93-96

The aim of the article is to describe the development of the principles of medicine based on the evidence (EBM) based on postulates of Robert Koch, Nobel prize winner, protagonist of the "Golden Age" medical bacteriology, founder of a concept of modern microbiology and infectology. Kochs work led to the discovery of a causal relationship between exposure to a specific pathogen and disease on the example of identifying the cause of anthrax - Bacillus anthracis, a disease whose symptoms vary depending on the mode of transmission (gastrointestinal ingestion, cutaneous form on contact and pulmonary manifestations when inhaled). Tuberculosis caused by Kochs bacillus, Mycobacterium tuberculosis, yet still affecting 1.7 billion people (about 25 % of the world's population), in 95 % of cases in developing countries, where poverty and high prevalence of HIV are part of everyday life. Koch also discovered Vibrio cholerae, the pathogen responsible for seven recorded pandemics, and hitherto sporadic epidemics in recent years. The main contribution of the Kochs four postulates formulation was the principle, which helped to reveal the causal relationship between the pathogenic microbe to protrude infectious disease and obtain reliable evidence in improving credibility of diagnosis of infectious diseases. Other stages in the development of EBM were formulated by Bradford Hill in his nine principles, which are valid as well for noncommunicable diseases. The subjects of discussion are limitations and restrictions of present EBM and its essentials and the use in rational preventive, diagnostic and treatment strategies.
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June 2021

Differences in risk factors for molecular subtypes of clear cell renal cell carcinoma.

Int J Cancer 2021 May 31. Epub 2021 May 31.

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

The ccA and ccB molecular subtypes of clear cell renal cell carcinoma (ccRCC) have well-characterized prognostic relevance. However, it is not known whether they possess distinct etiologies. We investigated the relationships between these subtypes and RCC risk factors within a case-control study conducted in Eastern Europe. We analyzed risk factor data for ccA (n = 144) and ccB (n = 106) cases and 1476 controls through case-only and case-control comparisons to assess risk factor differences across subtypes using logistic and polytomous regression models. We also performed a meta-analysis summarizing case-only results from our study and three patient cohorts. Patients with ccB tumors had poorer survival than those with ccA tumors and were more likely to be male (case-only odds ratio [OR] 2.68, 95% confidence interval [CI] 1.43-5.03). In case-control analyses, body mass index was significantly associated with ccA tumors (OR 2.45, 95% CI 1.18-5.10 for ≥35 vs <25 kg/m ) but not with ccB tumors (1.52, 0.56-4.12), while trichloroethylene was associated with ccB but not ccA (OR 3.09, 95% CI 1.11-8.65 and 1.25, 0.36-4.39 respectively for ≥1.58 ppm-years vs unexposed). A polygenic risk score of genetic variants identified from genome-wide association studies was associated with both ccA and, in particular, ccB (OR 1.82, 1.11-2.99 and 2.87, 95% CI 1.64-5.01 respectively for 90th vs 10th percentile). In a meta-analysis of case-only results including three patient cohorts, we still observed the ccB excess for male sex and the ccA excess for obesity. In conclusion, our findings suggest the existence of etiologic heterogeneity across ccRCC molecular subtypes for several risk factors.
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http://dx.doi.org/10.1002/ijc.33701DOI Listing
May 2021

Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer.

Scand J Work Environ Health 2021 May 3. Epub 2021 May 3.

Jan Hovanec, IPA, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.

Objectives: We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer.

Methods: In 13 case-control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands - each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman's Standard International Occupational Prestige Scale) were affected by adjustment for the job indices.

Results: In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56-1.93), PSI 1.33 (95% CI 1.17-1.51)] and women [PHI 1.62 (95% CI 1.24-2.11), PSI 1.31 (95% CI 1.09-1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32-1.58) to 1.30 (95% CI 1.17-1.45)], but not PSI.

Conclusions: Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.
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http://dx.doi.org/10.5271/sjweh.3967DOI Listing
May 2021

NATO and evidence-based military and disaster medicine: case for Vigorous Warrior Live Exercise Series.

Cent Eur J Public Health 2020 Dec;28(4):325-330

Ministry of Defence of the Czech Republic, Prague, Czech Republic.

The North Atlantic Treaty Organization (NATO) is the premier and only security alliance uniting 30 countries and growing with many partner states in the provision of collective security and against threats posed by conflict and natural disasters. Security of countries and communities is increasingly threatened by a broad spectrum of unconventional types of war and disease threats - from hybrid and asymmetric to multi-domain and peer-to-peer/near-peer conflict. The NATO Centre of Excellence for Military Medicine (MILMED COE) is the centre of gravity for medical best practices and promotion of medical doctrine across the NATO alliance. Disaster medicine is multidisciplinary and in NATO, multinational, requiring best practices that are driven by data and evidence to prevent death on the battlefield and prepare for future conflicts. "Vigorous Warrior" is a live military and disaster medicine exercise series using both civilian and military actors across all sectors of health focused on health security and identifying lessons learned to ready the alliance for future threats. In this brief report, we make the case that the Vigorous Warrior exercise exposes gaps, highlights challenges and generates an evidence base to make NATO military medicine systems more robust, more efficient and in provision of best medical practices. We specifically argue that clinical data capture must be duplicated and continuous across the alliance to ensure evidence-based medicine stays current in NATO military medical doctrine.
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http://dx.doi.org/10.21101/cejph.a6045DOI Listing
December 2020

Occurrence of acrylamide in selected food products.

Cent Eur J Public Health 2020 Dec;28(4):320-324

Institute of Hygiene, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.

Objective: Acrylamide is a toxic compound found in occupational and non-occupational environment. It originates from industrial use, technological processes in construction as well as food production, water purification, and laboratory use. Adverse effects including neurotoxicity, probably carcinogenicity, genotoxicity, teratogenicity, and reproductive toxicity were reported in many studies. Our study is focused on acrylamide content in selected food products in the Czech Republic.

Method: In this study, we determined acrylamide content in selected samples of commonly consumed food products (potato chips, biscuits, popcorn, corn flakes, breakfast cereals, and baked muesli).

Results: The concentration of acrylamide in most samples of potato chips, biscuits and popcorn exceeded the benchmark limits. The acrylamide content in samples of potato chips from one manufacturer in 4 cases out of 5 analysed samples exceeded benchmark limit. On the other hand, no corn flakes sample acrylamide content from the same manufacture exceeded the benchmark limit. With 20 of all analysed samples exceeding the benchmark levels for acrylamide, it can be concluded that 47.6% of samples did not comply with the benchmark level.

Conclusion: Dietary intake of frequently consumed food products with the acrylamide content exceeding the recommended comparative value could have adverse effects on the human health. Our study confirmed high amount of acrylamide in some selected food samples. The reduction of dietary burden with acrylamide is possible by complying with the correct technological principles in food preparation.
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http://dx.doi.org/10.21101/cejph.a6430DOI Listing
December 2020

Psychosomatic and psychosocial aspects of health risks perception rising from living and occupational settings.

Authors:
Vladimír Bencko

Cas Lek Cesk 2020 ;159(5):192-195

Psychosocial aspects may be of paramount importance in perceiving potential health risks. This is especially true when our knowledge of the real health implications of human exposure to the environmental risk factor is incomplete, or the intensity of this exposure is in the range of doubts as to possible biological effects. The most serious feature of these situations, particularly among psychologically labile individuals, is the presence of often severe neuropsychic and psychosomatic problems. Despite the difficult objectification, they pose different degrees of difficulty for the wearer to suffering, which cannot be underestimated in terms of the quality of their lives. Qualified assessment of potential health risks in the living and working environment, related to existing buildings and planned industrial, transport or other building activities/projects, is an essential part of their audit. While the initial phase of the risk assessment, namely its identification and exposure assessment, are of a purely natural nature, the self-estimation of the risk level already includes increasingly arbitrary aspects (e.g. safety factors). Risk communication and in particular risk management mean that, in the psychosocial terms, decision making is then put into a political context. The prevention of these problems can be systematic and timely educational or explanatory activity, targeted health education at the time of preparation of industrial, transport, military or other constructions and the use and involvement of local civic activists or activities. It does not have to be a cheap risk-shuffling but a clear convincing of the carrying capacity of the measure, with the advantages that the project will bring. Additional attempts to explain to the public the real state of affairs are usually accepted with distrust of hatred, with the information being “well-paid” misinformation that conceal the true state of affairs.
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December 2020

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

Occup Environ Med 2021 04 28;78(4):269-278. Epub 2020 Oct 28.

Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.

Objectives: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project.

Methods: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens.

Results: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0).

Conclusions: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.
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http://dx.doi.org/10.1136/oemed-2020-106770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958079PMC
April 2021

Study design, size, and adequate exposure data as the crucial aspects in cancer risk assessment and implementation of the precautionary principle.

Cent Eur J Public Health 2020 10;28 Suppl:S65-S68

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Traditional approaches and study design in cancer epidemiology have not been very successful in identifying and evaluating adequately the potential risk and/or protective factors associated with the disease. The main reasons for the failure are often due the small study sample size, and inadequate exposure information. In this paper, issues and approaches relevant to these two challenges are discussed. Multicentre study is proposed as a way to increase study size and to mitigate criticism about meta-analysis of independent studies. A multicentre study of large cohort or case-control studies also offer an exciting opportunity to study the contribution of epigenetic events that may be associated with lifestyle and environmental risk factors for human health. Optimizing methods for exposure assessment and how to reduce exposure to misclassification represent a difficult component in epidemiological studies. A potentially useful approach for improving exposure estimation is to rely on biomarkers of exposures. An example is provided to demonstrate how biomarkers of exposures could provide valuable information in addition to exposure measurements in traditional epidemiological studies. Finally, it is argued that risk assessment and the precautionary principle should not be viewed as conflicting paradigms but, rather, as a complementary approach for developing appropriate policies to address risks posed by exposure to carcinogens and a wide spectrum of other health hazards.
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http://dx.doi.org/10.21101/cejph.a6159DOI Listing
October 2020

Risk of exposure to acrylamide.

Cent Eur J Public Health 2020 10;28 Suppl:S43-S46

Department of the Environment, Veterinary Legislation and Economy, University of Veterinary Medicine and Pharmacy, Kosice, Slovak Republic.

Objectives: Acrylamide is a toxic compound that can be found it both occupational and non-occupational environments. This study focuses on its sources and health effects of its exposure.

Methods: Adverse effects of acrylamide, especially carcinogenic, genotoxic, and teratogenic were reported in many studies conducted on animals. Neurotoxicity was reported in workers exposed to acrylamide in the occupational environment. Another important source of populations' exposure to acrylamide is their nutrition.

Results: This study focuses on humans' exposure to acrylamide from various sources and its harmful effects on their health.

Conclusions: Dietary intake of acrylamide, as well as occupational exposure, cigarette smoking, cosmetics usage and other environmental sources could have a significant effect on human health.
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http://dx.doi.org/10.21101/cejph.a6177DOI Listing
October 2020

The presence of fine and ultrafine particulate matter in the work environment.

Cent Eur J Public Health 2020 10;28 Suppl:S31-S36

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

This study presents the results of pilot measurement, where the exposure of fine and ultrafine particulate matter was monitored. The measurement was performed in welding workplace, where these particles are produced unintentionally. The measurement consisted of collecting information and measuring the concentration of particles in the workplace, where data collection was focused only on inhalation exposure. During welding, primarily 300 nm size particles are produced, and their concentration is strongly influenced by the welding material, type of welding and suction. The particles are amorphous in terms of morphology and contain manganese, iron and silicon, which can cause neurodegenerative diseases. Furthermore, the results indicate the importance of monitoring oral exposure.
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http://dx.doi.org/10.21101/cejph.a6174DOI Listing
October 2020

Health aspects of exposure to emissions from burning coal of high beryllium content: interactions with the immune system.

Cent Eur J Public Health 2020 Sep;28(3):198-201

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Beryllium has an impact on the human health of professionally or non-occupationally exposed people. Current evidence suggests that beryllium acts as a hapten with limited antigenic properties and is presented by antigen presenting cells to CD4 T cells, which possess specific antigen receptors. The immunological changes in humoral immunoreactivity were considered biomarkers of beryllium exposure. In the present, due to the development of immunologic knowledge, tests of cellular immunity have promising potential for further research in this field. The historical view of the immune response to beryllium in acute and/or chronic beryllium disease is an example of the development of the interaction between mechanisms of innate and adaptive (specific), humoral and cellular immunity. The authors emphasize the increasing importance of immunological aspects in the studies of health impacts of human exposure to environmental pollutants.
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http://dx.doi.org/10.21101/cejph.a5851DOI Listing
September 2020

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Am J Respir Crit Care Med 2020 08;202(3):402-411

Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and ll Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte (CPO-Piemonte), Torino, Italy.

Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes. We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations. We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined. We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.
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http://dx.doi.org/10.1164/rccm.201911-2101OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465091PMC
August 2020

Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case-Control Studies.

Am J Respir Crit Care Med 2020 08;202(3):412-421

The M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype. We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks. Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed. Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated ( trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated ( trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes. Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.
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http://dx.doi.org/10.1164/rccm.201910-1926OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465090PMC
August 2020

Sex specific associations in genome wide association analysis of renal cell carcinoma.

Eur J Hum Genet 2019 10 23;27(10):1589-1598. Epub 2019 Jun 23.

Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (OR) = 0.83 [95% CI = 0.78-0.89], P = 1.71 × 10 compared with female odds ratio (OR) = 0.98 [95% CI = 0.90-1.07], P = 0.68) and 12q23.3 (intergenic, OR = 0.75 [95% CI = 0.68-0.83], P = 1.59 × 10 compared with OR = 0.93 [95% CI = 0.82-1.06], P = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
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http://dx.doi.org/10.1038/s41431-019-0455-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777615PMC
October 2019

Added value of human biomonitoring in assessment of general population exposure to xenobiotics.

Cent Eur J Public Health 2019 Mar;27(1):68-72

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Human biomonitoring (HBM) has a wide range of applications and long tradition both in health care and the field of public health. Its major advantage is the integration of all exposure routes and sources. Since HBM information is an integrated exposure finding it offers the opportunity to trace and mimic a realistic exposure scenario. It reduces the number of assumptions that need to be made when estimating exposure and thus helps to reduce the uncertainties in exposure science. In spite of some challenges, such as further harmonization in the area of HBM, necessity of deriving equivalents of markers of external exposure and addressing the ethical and political aspects of its application, HBM is an efficient and cost-effective way to measure exposure levels of the human body to xenobiotics.
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http://dx.doi.org/10.21101/cejph.a5348DOI Listing
March 2019

The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.

PLoS Med 2019 01 3;16(1):e1002724. Epub 2019 Jan 3.

National Institute of Public Health, Bucharest, Romania.

Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.

Methods And Findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.

Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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http://dx.doi.org/10.1371/journal.pmed.1002724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317776PMC
January 2019

A horizontal transmission of genetic information and its importance for development of antibiotics resistance.

Cas Lek Cesk Summer 2018;157(3):141-145

Genetic information is transmitted among organisms through two pathways - vertically from generation to generation (from parents to progeny) and horizontally (laterally) by direct exchange of genetic material across species barriers. These are primarily prokaryotes, in which the exchange of genes or whole gene segments by horizontal transmission is quite common. They can dynamically and in a relatively short time generate highly diverse genomes, which does not allow the vertical transmission. As a result, prokaryotes can rapidly acquire new properties such as virulence and pathogenicity as well as resistance to toxins, including antibiotics, by which they increase their adaptability. Therefore, reinfection-resistant microorganisms are always more difficult to treat than infections caused by non-resistant bacteria. Antibiotic resistance today is a global problem of health care service. Not only does the number of diseases caused by resistant pathogenic strains of bacteria increase, but also the cost of treatment increases disproportionately, the length of hospitalization is prolonged, and mortality is often rising. Therefore, when indicating antibiotic therapy, it is important to keep in mind that both overuse and abuse of antibiotics contribute to the spread of antibiotic resistance genes. This is equally true for antibiotic applications in veterinary medicine, agriculture, including aquacultures, or in the food industry. Keywords: horizontal transmission of genetic information, endosymbiosis, antibiotic resistance, risks of the emergence and spread of antibiotic resistance, prevention of antibiotic resistance.
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April 2019

Retrospective assessment of specific effects of exposure of workers to PCBs in Slovakia.

Ann Agric Environ Med 2018 Sep 9;25(3):421-427. Epub 2018 Apr 9.

1st Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University, Prague, Czech Republic.

Introduction And Objective: Polychlorinated biphenyls (PCBs) have been used commercially since 1929 as dielectric and insulating non-flammable substances, additives for paints, etc. In Slovakia, 60 chemical production workers highly exposed to PCBs (mainly to Delor 103) were studied with duration of exposure ranging from 3 months to 19 years.

Material And Methods: Clinical examinations of skin, skin histology and laboratory tests concerning lipid metabolism, iron metabolism and levels of copper provided comparisons with a control group of healthy individuals and/or the upper limits of normal values.

Results: Skin changes were found in 47 % of individuals. In most cases, milia-like efflorescences (57.14 %) occurred, as well as comedones (55.35 %); other symptoms occurred in a smaller number of workers. Hyperkeratosis, acanthosis of the epidermis (particularly in hair follicles), and a cellular infiltration of the corium were all found through histology. The intensity of cutaneous affections was associated with the changes in laboratory tests. Elevated triglycerides, cholesterol, and phospholipids were found in exposed workers. After a further two years, a significant increase in triglycerides was found in exposed individuals when compared with the control group. In addition, a significant increase in serum levels of copper, and total and unsaturated iron-binding capacity was detected.

Conclusions: Anamnesis showed that some people directly exposed to PCBs may develop skin changes after three months of occupational exposure. The results represent a unique snapshot of worker exposure at a given location, representing the basis for comparison with the population who grew up in the area and still live there today.
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http://dx.doi.org/10.26444/aaem/86307DOI Listing
September 2018

Fish and fish products as risk factors of mercury exposure.

Ann Agric Environ Med 2018 Sep 23;25(3):488-493. Epub 2018 Mar 23.

Charles University in Prague, 1st Faculty of Medicine, Institute of Hygiene and Epidemiology, Czech Republic.

Introduction: Mercury is ubiquitous in the biosphere, occurring in the air, water, land, and soil, as well as in living organisms. Excessive exposure to mercury is associated with a wide range of adverse health effects including damage to the central nervous system and the kidneys. Mercury exists in many different forms in the environment which produce various patterns of toxicity. Protection of the food chain from contamination by mercury is an important task in the protection of health of the human population.

Objective: The aim of the study was to monitor the concentrations of mercury in fish and fish products from food retail in Eastern Slovakia, and from the Ružín water reservoir, Košice district.

Material And Methods: A total of 384 samples of fish and fish products were collected for the study. Atomic absorption spectrometry standard solutions for mercury were used at a wavelength of 254 nm.

Results: The majority of countries and global organizations now enforce a maximum concentration of mercury in fish of approximately 0.5 mg.kg-1. All of the 184 samples (50.52 % of the total fish samples studied) were above the maximum level set by the European Commission Regulation for mercury in fish.

Conclusions: The systematic analytical control of contaminants in food is important. Mercury is concentrated in seafood, products of prey and marine fish, fish from rivers and lakes in the areas contaminated by mercury. According to the findings of this study with analyzer AMA 254, the consumption is not recommended of fish, especially seafood (meat of shark, swordfish and king mackerel), for selected groups of the population: children, women of childbearing age, pregnant women and nursing mothers.
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http://dx.doi.org/10.26444/aaem/84934DOI Listing
September 2018

Debate: the per rectal/digital rectal examination exam in the emergency department, still best practice?

Int J Emerg Med 2018 Mar 27;11(1):20. Epub 2018 Mar 27.

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.

Background: Emergency medicine practice in the UK and Ireland offers a junior and middle grade doctor great learning opportunities that force engagement with multiple specialties, life-saving procedures, exposure to a myriad of patient presentations, and opportunities for best practices in medicine.

Main Body: The emergency department (ED) can be a hectic and dynamic environment; communication from the ED to specialists is essential to ensure best clinical outcomes for patients. The "per rectal" (PR) or "digital rectal exam" (DRE) can be a very difficult diagnostic test for even the most skilled operator to discern pathological versus normal; we propose this is especially the case in the emergency department patient population. Some specialists require this exam performed by an unskilled junior doctor with varying results prior to reviewing a referred and sick patient. The PR/DRE benefits may be limited in the ED setting for some pathologies, and the result of the exam may have limited impact in the overall treatment plan in the ED.

Conclusion: This short paper reviews the indications, benefits, shortfalls, and limitations of the PR/DRE in the emergency department setting and offers novel alternatives to maximize best practice, ensure best clinical outcomes for patients, and, to first, do no harm.
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http://dx.doi.org/10.1186/s12245-018-0165-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871612PMC
March 2018

Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis.

Sci Rep 2018 03 14;8(1):4534. Epub 2018 Mar 14.

Section of Hygiene, Institute of Public Health, Università Cattolica del Sacro Cuore, IRCCS Fondazione Policlinico 'Agostino Gemelli', Rome, Italy.

With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.
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http://dx.doi.org/10.1038/s41598-018-22626-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852094PMC
March 2018

Prehospital Medicine and the Future Will ECMO Ever Play a Role?

J Spec Oper Med Spring 2018;18(1):133-138

Due to the hybrid warfare currently experienced by multiple NATO coalition and NATO partner nations, the tactical combat casualty care (TCCC) paradigm is greatly challenged. One of the major challenges to TCCC is the ad hoc extension phase in resource-poor environments, referred to as prolonged field care (PFC) and forward resuscitative care (FRC). The nuanced clinical skills with limited resources required by warfighters and auxiliary health care professionals to mitigate death on the battlefield and prevent morbidity and mortality in the PFC phase represent a balance that is still under review. The aim of our article is to describe the connection between extracorporeal membrane oxygenation (ECMO) or the extracorporeal life support (ECLS) treatment and its possible improvement in prehospital trauma care, at a Role 1 or 2 facility and, more provocatively, in the PFC phase of care in the future through innovative technology and how it connects with FRC. We report and describe here the primary components of ECMO/ECLS and present the main concept of a human extracorporeal circulation cocoon as a transitional living form for the cardiopulmonary stabilization of wounded combatants on the battlefield and their transportation to higher echelons of care and treatment facilities (to include damage control resuscitation [DCR] and damage control surgery [DCS]). As clinical governance, these matters would fall within the remit of the Committee on Surgical Combat Casualty Care (CoSCCC) and the Committee on Enroute Combat Casualty Care (CoERCCC), and it is within this framework that we propose this concept piece of ECMO in the prehospital space. We caution that this report is a proposed innovation to TCCC but also serves to push the envelope of the PFC and FRC paradigm. What we propose will not change the practice this year, but as ECMO technology progresses, it may change our practice within the next decade. We conclude with proposed novel future research to save life on the battlefield with ECMO as a major challenge and one worth the focus of further research. Medicine is controversial and constantly changing; for those who work in prehospital and battlefield medicine, change is the only constant on which we rely, and without provocative discussion that makes our systems and practice more robust, we will fail.
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May 2018

Lung cancer and socioeconomic status in a pooled analysis of case-control studies.

PLoS One 2018 20;13(2):e0192999. Epub 2018 Feb 20.

National Institute of Public Health, Bucharest, Romania.

Background: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study.

Methods: Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens.

Results: The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)).

Conclusion: SES remained a risk factor for lung cancer after adjustment for smoking behavior.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192999PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819792PMC
April 2018

Public Health Crisis: the Need for Primary Prevention in Failed and Fragile States.

Cent Eur J Public Health 2017 Sep;25(3):171-176

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Objective: A new 'normal' in global affairs may be erupting from large global powers to that of non-state actors and proxies committing violence through scaled conflict in a post-Westphalian world generating significant global health policy challenges. Health security of populations are multifactorial and indirectly proportional to war, conflict and disaster. Preventing conflict and avoiding the health vacuum that occurs in war and violence may be best practices for policy makers. This paper considers an approach of applying clinical primary prevention principles to global health policy.

Methods: Brief policy review of current standards and practices in health security in fragile and failed states and prevention; and definitions discussion. A short case study series are presented with best practices, with risk and outcome review.

Results: The global balance of power and order may be shifting through geopolitical transference and inadequate action by major global power brokers. Health security in at risk nation-states may be decreasing as a result.

Conclusion: Small scale conflict with large-scale violence threatens health security and may experience increased incidence and prevalence in fragile and failed states. Preventative policy to resuscitate fragile and failed states and prevent further external and internal shocks may support health and promote a positive feedback loop of further state stability and increased health security. Public health policy shift to mitigate state failure and public health crisis in war and conflict through the basis of primary prevention may provide best practices and maximize health security for at risk populations.
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http://dx.doi.org/10.21101/cejph.a4671DOI Listing
September 2017

Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.

Eur Urol 2017 11 7;72(5):747-754. Epub 2017 Aug 7.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, MS, USA.

Background: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.

Objective: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.

Design, Setting, And Participants: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.

Outcome Measurements And Statistical Analysis: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.

Results And Limitations: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).

Conclusions: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.

Patient Summary: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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http://dx.doi.org/10.1016/j.eururo.2017.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641242PMC
November 2017

The history of arsenical pesticides and health risks related to the use of Agent Blue.

Ann Agric Environ Med 2017 Jun 12;24(2):312-316. Epub 2017 Jun 12.

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Arsenicals in agriculture. Beginning in the 1970s, the use of arsenic compounds for such purposes as wood preservatives, began to grow. By 1980, in the USA, 70% of arsenic had been consumed for the production of wood preservatives. This practice was later stopped, due to the US Environmental Protection Agency (EPA) ban of the arsenic-and chromium-based wood preservative chromated copper arsenate. In the past, arsenical herbicides containing cacodylic acid as an active ingredient have been used extensively in the USA, from golf courses to cotton fields, and drying-out the plants before harvesting. The original commercial form of Agent Blue was among 10 toxic insecticides, fungicides and herbicides partially deregulated by the US EPA in February 2004, and specific limits on toxic residues in meat, milk, poultry and eggs, were removed. Today, however, they are no longer used as weed-killers, with one exception - monosodium methanearsonate (MSMA), a broadleaf weed herbicide for use on cotton. Severe poisonings from cacodylic acid caused headache, dizziness, vomiting, profuse and watery diarrhea, followed by dehydration, gradual fall in blood pressure, stupor, convulsions, general paralysis and possible risk of death within 3-14 days.The relatively frequent use of arsenic and its compounds in both industry and agriculture points to a wide spectrum of opportunities for human exposure. This exposure can be via inhalation of airborne arsenic, contaminated drinking water, beverages, or from food and drugs. Today, acute organic arsenical poisonings are mostly accidental. Considerable concern has developed surrounding its delayed effects, for its genotoxic and carcinogenic potential, which has been demonstrated in epidemiological studies and subsequent animal experiments. Conclusions. There is substantial epidemiological evidence for an excessive risk, mostly for skin and lung cancer, among humans exposed to organic arsenicals in occupational and environmental settings. Furthermore, the genotoxic and carcinogenic effects have only been observed at relatively high exposure rates. Current epidemiological and experimental studies are attempting to elucidate the mechanism of this action, pointing to the question whether arsenic is actually a true genotoxic, or rather an epigenetic carcinogen. Due to the complexity of its effects, both options remain plausible. Its interactions with other toxic substances still represent another important field of interest.
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http://dx.doi.org/10.26444/aaem/74715DOI Listing
June 2017

Levels and Health Risk Assessment of PM Aerosol in Brno, Czech Republic.

Cent Eur J Public Health 2017 06;25(2):129-134

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Objective: The main effort of this work was to evaluate the situation of the atmosphere in selected regions of Brno during the years 2009-2013 and to estimate health risks which might come up due to the increased concentrations of airborne particulate matter.

Methods: PM samples were collected in four areas varying in degree of automobile traffic using automatic and gravimetric sampling methods. PM concentrations were assessed using Spearman's rank correlation coefficient. Health risks were estimated based on calculation of relative risks and population for four health endpoints. The selected health outcomes were premature mortality, cardiovascular disease, respiratory disease, and chronic bronchitis.

Results: The highest PM concentrations were measured in two regions with high traffic loads T1, T2 and background region B2. The values were 34.33 ± 11.52 µg·m in 2010, 34.87 ± 12.03 µg·m in 2013 and 34.52 ± 8.81 µg·m in 2009, respectively. The highest correlation was between T1 and T2 having Spearman's correlation coefficient 0.888 followed by T1-B1 pair with coefficient 0.886. For all health outcomes, the highest health effect of PM (E) was determined for T2 site in 2010 which was 48 ± 14, 49 ± 21, 44 ± 19 and 24 ± 10 for premature mortality, cardiovascular disease, respiratory disease, and chronic bronchitis, respectively.

Conclusion: The concentrations are highly correlated, especially in traffic regions. The annual concentrations did not exceed the legislation limit but 24-hours limit was exceeded more than two times in several cases. The highest number of cases with a given health outcome was estimated in traffic regions especially for cardiovascular disease and premature mortality.
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http://dx.doi.org/10.21101/cejph.a4495DOI Listing
June 2017

Genome-wide association study identifies multiple risk loci for renal cell carcinoma.

Nat Commun 2017 06 9;8:15724. Epub 2017 Jun 9.

Clinical Center of Serbia (KCS), Clinic of Urology, University of Belgrade-Faculty of Medicine, 11000 Belgrade, Serbia.

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10), 3p22.1 (rs67311347, P=2.5 × 10), 3q26.2 (rs10936602, P=8.8 × 10), 8p21.3 (rs2241261, P=5.8 × 10), 10q24.33-q25.1 (rs11813268, P=3.9 × 10), 11q22.3 (rs74911261, P=2.1 × 10) and 14q24.2 (rs4903064, P=2.2 × 10). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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http://dx.doi.org/10.1038/ncomms15724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472706PMC
June 2017

Public Health Crisis in War and Conflict - Health Security in Aggregate.

Cent Eur J Public Health 2017 03;25(1):72-76

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Objective: Public health status of populations is multifactorial and besides other factors it is linked to war and conflict. Public health crisis can erupt when states go to war or are invaded; health security may be reduced for affected populations.

Methods: This study reviews in aggregate multiple indices of human security, human development and legitimacy of the state in order to describe a predictable global health portrait.

Results: Paradigm shift of large global powers to that non-state actors and proxies impact regional influence through scaled conflict and present major global health challenges for policy makers. Small scale conflict with large scale violence threatens health security for at-risk populations.

Conclusions: The paper concludes that health security is directly proportional to state security.
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http://dx.doi.org/10.21101/cejph.a4455DOI Listing
March 2017