Cumulative Exposure Dose Research Articles

Long-term morbidity and mortality in 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies.

Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease. We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients. With a median follow-up of 9.4years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis. With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.

Ultraviolet-B irradiance and cumulative dose combine to determine performance and survival.

Despite decades of research, the role of elevated solar ultraviolet-B radiation (UVBR; 280-315nm) in shaping amphibian populations remains ambiguous. These difficulties stem partly from a poor understanding of which parameters of UVBR exposure - dose, irradiance, and time interval - determine UVBR exposure health risk, and the potentially erroneous assumption that effects are proportional to the dose of exposure, irrespective of the administered regime (Bunsen-Roscoe Law of Reciprocity; BRL). We tested if the BRL holds with respect to UVBR-induced physiological effects in amphibians by acutely exposing tadpoles of the Australian green tree frog (Litoria caerulea) to a combination of different UVBR irradiances and doses in a fully factorial experiment. The BRL was invalid across all metrics assessed, with UVBR irradiance influencing the effects of a given dose on growth, coloration and burst swimming performance of larvae. We demonstrated some of the first empirical evidence for beneficial physiological effects of UVBR exposure in a larval amphibian, with improvements in growth, burst swimming performance and survival at the highest UVBR doses, contrary to hypotheses. Our findings demonstrate the species-specific nature of amphibian responses to UVBR, and the importance of UVBR irradiance in influencing the long-term physiological effects of a given dose of radiation. This work enhances our understanding of which parameters of complex UVBR exposures determine amphibian health risk.

A patient decision aid for mild asthma: Navigating a new asthma treatment paradigm

IntroductionIn mild asthma, as-needed budesonide-formoterol offers similar protection from severe exacerbations as daily inhaled corticosteroids (ICS), with lower ICS exposure but slightly increased symptoms. We sought to develop an electronic decision aid to guide discussions about the pros and cons of these first-line options, while identifying and integrating user preferences. MethodsFollowing International Patient Decision Aid Standards, we created a mild asthma decision aid prototype comparing convenience, clinical outcomes, cumulative ICS dose exposure, costs, and side-effects of each option. After face validation, the prototype was iteratively adapted through rapid-cycle development. Each cycle consisted of a patient focus group and a primary care physician interview. We made user preference-based improvements after each round, until reaching a pre-set stopping criterion (no new critical issues identified). We then performed a summative qualitative content analysis. ResultsOver 5 cycles, we recruited 21 asthma patients (12/21 women, 10/21 ≥ 60 years old) and 5 physicians. Serial changes included simplification and reduction of text and reading level, inclusion of an ICS “myths” section and elaboration of patient-friendly infographics for numerical comparisons. User preferences fell within Content, Format, and tool use Process themes. In response to decision-making preferences, we created a complementary one-page conversation aid for patient-provider use at the point-of-care. ConclusionsWe present preference-based electronic patient decision and conversation aids for treatment of mild asthma. Our user preference analyses offer useful insights for development of such tools in other chronic diseases. These tools now require integration into point-of-care workflows for measurement of real-world uptake and impact.

Study Protocol for Radiation Exposure and Cancer Risk Assessment: The Taiwan Nuclear Power Plants and Epidemiology Cohort Study (TNPECS).

This cohort was established to evaluate whether 38-year radiation exposure (since the start of nuclear reactor operations) is related to cancer risk in residents near three nuclear power plants (NPPs). This cohort study enrolled all residents who lived within 8 km of any of the three NPPs in Taiwan from 1978 to 2016 (n = 214,502; person-years = 4,660,189). The control population (n = 257,475; person-years = 6,282,390) from three towns comprised all residents having lived more than 15 km from all three NPPs. Radiation exposure will be assessed via computer programs GASPAR-II and LADTAP-II by following methodologies provided in the United States Nuclear Regulatory Commission regulatory guides. We calculated the cumulative individual tissue organ equivalent dose and cumulative effective dose for each resident. This study presents the number of new cancer cases and prevalence in the residence-nearest NPP group and control group in the 38-year research observation period. TNPECS provides a valuable platform for research and opens unique possibilities for testing whether radiation exposure since the start of operations of nuclear reactors will affect health across the life course. The release of radioactive nuclear species caused by the operation of NPPs caused residents to have an effective dose between 10-7 and 10-3 mSv/year. The mean cumulative medical radiation exposure dose between the residence-nearest NPP group and the control group was not different (7.69; standard deviation, 18.39 mSv and 7.61; standard deviation, 19.17 mSv; P = 0.114).

Maternal and iatrogenic neonatal opioid withdrawal syndrome: Differences and similarities in recognition, management, and consequences.

Opioids are potent analgesics used to manage pain in both young and old, but the increased use in the pregnant population has significant individual and societal implications. Infants dependent on opioids, either through maternal or iatrogenic exposure, undergo neonatal opioid withdrawal syndrome (NOWS), where they may experience withdrawal symptoms ranging from mild to severe. We present a detailed and original review of NOWS caused by maternal opioid exposure (mNOWS) and iatrogenic opioid intake (iNOWS). While these two entities have been assessed entirely separately, recognition and treatment of the clinical manifestations of NOWS overlap. Neonatal risk factors such as age, genetic predisposition, drug type, and clinical factors like type of opioid, cumulative dose of opioid exposure, and disease status affect the incidence of both mNOWS and iNOWS, as well as their severity. Recognition of withdrawal is dependent on clinical assessment of symptoms, and the use of clinical assessment tools designed to determine the need for pharmacotherapy. Treatment of NOWS relies on a combination of non-pharmacological therapies and pharmacological options. Long-term consequences of opioids and NOWS continue to generate controversy, with some evidence of anatomic brain changes, but conflicting animal and human clinical evidence of significant cognitive or behavioral impacts on school-age children. We highlight the current knowledge on clinically relevant recognition, treatment, and consequences of NOWS, and identify new advances in clinical management of the neonate. This review brings a unique clinical perspective and critically analyzes gaps between the clinical problem and our preclinical understanding of NOWS.

Chloroquine and Hydroxychloroquine Myopathy: Clinical Spectrum and Treatment Outcomes.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been associated with muscle toxicity, mostly described as a proximal myopathy with evidence of lysosomal dysfunction on muscle biopsy. In this retrospective study, we aimed to define the clinical phenotype, laboratory features, and treatment outcomes of CQ/HCQ myopathy, as well as the safety profile of these drugs. We identified 13 patients seen between 2000 and 2019, with a median age at presentation of 66 years (range 53–89); 11 were females. At onset of symptoms, patients were on CQ or HCQ for a minimum of 6 months and up to 21 years. Diagnosis was often delayed by a median of 6 months (range 3–48). At presentation, 13 patients reported limb weakness, with five requiring assistance in walking. Ten reported dysphagia, often severe, resulting in marked weight loss or aspiration pneumonia. Nine reported respiratory symptoms, which were multifactorial in four, and four reported severe neck weakness. Myopathy clinical phenotype showed predominant involvement of one or more of the following: proximal limb muscle weakness (12 patients), dysphagia (9), axial weakness (4), and respiratory failure (5). Eleven patients had a cardiac evaluation showing prolonged QT interval in 10 and CQ/HCQ cardiomyopathy (CMP) in four. Ten out of 12 patients markedly improved after discontinuing the medication, but most were left with some residual weakness. Eleven patients had a muscle biopsy showing a myopathy with rimmed vacuoles and marked acid phosphatase reactivity. Nine had elevated creatine kinase level up to 1,199 U/L. Twelve patients had an electromyography (EMG), which showed myopathic motor unit potentials with fibrillation potentials in 11 and myotonic discharges in 3. Higher cumulative dose and longer exposure duration were associated with more severe disability and more common cardiac and swallow involvement, indicating a cumulative dose effect. Herein, we demonstrate that long-term exposure to CQ and HCQ may result in a myopathy with a wide spectrum of clinical presentation and predilection for swallowing, respiratory, and cardiac muscles, often with marked associated morbidity. Once accurately diagnosed and the drug is discontinued, patients usually improve but often fail to return to baseline.

Bone Disruption and Environmental Pollutants

Endocrine Disrupting Chemicals (EDCs) are ubiquitous and may significantly contribute to environmental pollution and contamination in humans and wildlife. Ecological pollutants could interfere with bone homeostasis through different mechanisms, including hormonal imbalance, direct osteoblast toxicity, and enhancement of osteoclasts activity, leading to either osteopenia or osteoporosis. Among these chemicals, bisphenols, dioxins, polycyclic aromatic hydrocarbons, polychlorobiphenyls, poly- and perfluoroalkyl, phthalates, parabens, organotins, and cadmium may play a role in the bone disruption. Authors searched PubMed/MEDLINE, ISI-web of knowledge, and Google scholar databases for medical subject headings terms and free-text words related to the classes mentioned above of chemicals and bone metabolism and remodeling for better clarifying and understanding the main mechanisms of bone disruption. Several EDCs act as xeno-estrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties. Much evidence about bone disruptors was obtained from in vitro studies or animal models with equivocal results. Besides, a few data have been acquired from humans, and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, humans may be exposed to a mixture of EDCs, and the final effect on bone metabolism might be attributable to either synergistic or antagonist effects. Age of first exposure, cumulative exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other essential variables influencing bone metabolism's final effect. Given these variables, observational studies are needed to analyze this issue for ecological purposes better and preserve bone health.

Calculation of Electric Field Distribution in the Simulating Device for Animal Experiment

A main way to investigate the biological effects of 50Hz electromagnetic field is to conduct animal experiments by using the simulating device of 50Hz electromagnetic field. In order to determine the exposure strength of experimental animals in rearing cages in simulating device more accurately, the distribution of electric field should be simulated. Based on ANSYS, a software of finite element analysis, we simulated two-dimensional (2D) electric field distribution of the proposed simulating device of high voltage 50Hz electric field for a case when there were no rearing cages, and we validated those simulation results by comparison with actual measurements. Additionally, we simulated three-dimensional (3D) electric field distribution in the rearing cages for the cases when there was one rearing cage and when there were 8 rearing cages in the simulating device respectively. The simulation results showed that distribution of 50Hz electric field in rearing cage was not uniform when there were rearing cages in the simulating device, and the maximum difference was about 9kV/m. Therefore, based on the movement tracking of animals and the distribution of 50Hz electric field in rearing cages, the cumulative exposure dose of experimental animals could be determined accurately through integral method in order to increase the accuracy of experiments.

Inhaled corticosteroids in COPD and the risk for coronary heart disease: a nationwide cohort study

Inhaled corticosteroids (ICS) might lower the risk of coronary heart disease (CHD) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the association of ICS with the development of CHD in COPD patients by using data from the Korean Nationwide study. Patients who were newly diagnosed with COPD between 2004 and 2013 and who were not diagnosed with coronary heart disease before their diagnosis of COPD were included. Exposure of ICS was incorporated into multivariable Cox regression models using time-dependent methods. To accurately estimate ICS-exposure accumulation, a washout period of 2 years from 2002 to 2003 was applied. Among a total of 4,400 newly diagnosed COPD patients, 771 patients were diagnosed as CHD incident cases during a median follow-up of one year (interquartile range 0.1–2.9). The cumulative dose of ICS was associated with a reduced risk of CHD (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.52–0.89). When the cumulative exposure dose of ICS was divided into quartiles, the aHR for CHD incidence was 0.70 (95% CI, 0.55–0.88) in the highest quartile ICS dose use. The effect of ICS on reducing CHD incidence was pronounced in adults over 55 years, men under 55 years, and former smokers. Our findings demonstrate the role of ICS for the prevention of CHD in COPD patients without a history of CHD. Further research is needed to determine whether a certain amount of ICS exposure in COPD patients is protective against CHD.

Риск катаракты различных типов в когорте работников, подвергшихся профессиональному хроническому облучению

Purpose: To assess cataract type specific risks in a cohort of workers occupationally exposed to ionizing radiation over prolonged periods.
 Material and methods: The present retrospective cohort study included 22,377 workers first employed at a nuclear production facility in 1948–1982 and followed up till the end of 2008. By the end of the follow-up period in the study worker cohort 3123 cases of cortical cataract, 1239 cases of posterior subcapsular cataract (PSC) and 2033 cases of nuclear cataracts were registered over 486,245, 489,162, 492,004 person-years of follow-up, respectively.
 Results: The incidence of PSC, cortical and nuclear cataracts was significantly linearly associated with the cumulative radiation dose. The excess relative risk per unit dose of external gamma-ray exposure (ERR/Sv) was 0.91 (95 % CI: 0.67–1.20) for PSC, 0.63 (95 % CI: 0.49–0.76) for cortical cataracts and 0.47 (95 % CI: 0.35–0.60) for nuclear cataracts. Exclusion of an adjustment for neutron dose and inclusion of additional adjustments for body mass index and smoking index reduced ERRs/Sv for all types of cataracts. However, an additional adjustment for glaucoma increased the incidence risks of cortical and nuclear cataracts just modestly (but not for PSC). Inclusion of an adjustment for diabetes mellitus reduced the ERR/Sv of external gamma-ray exposure only for PSC incidence. Increased incidence risks of all cataract types were observed in both males and females of the study cohort, but ERR/Sv was significantly higher in females (p < 0.001), especially for PSC.
 Conclusion: The incidence of various types of cataracts in the cohort of workers occupationally chronically exposed to ionizing radiation was associated with the cumulative dose of external gamma-ray exposure.

Cumulative Radiation Exposure from Diagnostic Imaging in Zagazig University Pediatric Intensive Care and Chest Units

Background: The medical use of ionizing radiation has expanded worldwide. The use of radiation in pediatric imaging (e.g. radiographs and computed tomography) saves lives and has a great clinical value for the diagnosis of pediatric illness and injury. However, inappropriate or unskilled use of such technologies may result in unnecessary exposure that may increase risk of malignancy occurrence. Objective: To detect the effect of multi exposure and its application on reaching to risk threshold of radiation through quantification of the cumulative effective dose (CED) of ionizing radiation attributable to diagnostic imaging in Pediatric Intensive Care Unit (PICU) and Chest Unit, Zagazig University Hospitals. Also, to examine the patterns of use of diagnostic X-ray imaging in these units. Patients and Methods: This study was conducted in Pediatric ICU and Chest Unit at Zagazig University Hospital from October 2018 to March 2019. 72 cases were included. Selected cases were observed and followed up in each time they were asked to perform x-ray radiography or CT film during their whole stay period in the hospital. Results: The median of x-ray + ct group was 3 7.9 msv in our study. Also, in our study, there was dose variation among units. The median of exposure of patients of Chest Unit was 6.51. While the median of patients of ICU was 1.9. Dose of CT in our study formed 53.8%. Our study revealed that CT chest equaled about 30 chest X-ray in our hospital. 74% of patients had very low and low risks. Conclusion: Cumulative exposure dose (CED) of ionizing radiation due to frequent X-ray films and CT scans in our study aren’t likely to cause acute toxicity as they were relatively low but they may cause chronic toxicity and increases the long-term risk for developing malignancy.

An External Dose Assessment of Worker during RadWaste Treatment Facility Decommissioning

Background: Kori unit #1 is permanently shut down after a 40-year lifetime. The Nuclear Safety and Security Commission recommends establishing initial decommissioning plans for all nuclear and radwaste treatment facilities. Therefore, the Korea Atomic Energy Research Institute (KAERI) must establish an initial and final decommissioning plan for radwaste-treatment facilities. Radiation safety assessment, which constitutes one chapter of the decommissioning plan, is important for establishing a decommissioning schedule, a strategy, and cost. It is also a critical issue for the government and public to understand. Materials and Methods: This study provides a method for assessing external radiation dose to workers during decommissioning. An external dose is calculated following each exposure scenario, decommissioning strategy, and working schedule. In this study, exposure dose is evaluated using the deterministic method. Physical characterization of the facility is obtained by both direct measurement and analysis of the drawings, and radiological characterization is analyzed using the annual report of KAERI, which measures the ambient dose every month. Results and Discussion: External doses are calculated at each stage of a decommissioning strategy and found to increase with each successive stage. The maximum external dose was evaluated to be 397.06 man-mSv when working in liquid-waste storage. To satisfy the regulations, working period and manpower must be managed. In this study, average and cumulative exposure doses were calculated for three cases, and the average exposure dose was found to be about 17 mSv/yr in all the cases. Conclusion: For the three cases presented, the average exposure dose is well below the annual maximum effective dose restriction imposed by the international and domestic regulations. Working period and manpower greatly affect the cost and entire decommissioning plan; hence, the chosen option must take account of these factors with due consideration of worker safety.

The first, holistic immunological model of COVID-19: Implications for prevention, diagnosis, and public health measures.

The natural history of COVID‐19 caused by SARS‐CoV‐2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi‐organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10‐15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose‐binding lectin). If SARS‐CoV‐2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high‐affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low‐moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID‐19 facilitates re‐inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies ("viral auto‐inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This “quantitative and time‐/sequence‐dependent” model has several implications for prevention, diagnosis, and therapy of COVID‐19 at all ages.

The Dynamics of the Average Annual and Cumulative Radiation Exposure Doses of the Adult Population of the Russian Federation after the Chernobyl Disaster

The purpose of the study was to study the patterns of forming average annual and cumulative exposure doses. The subject of the study was the dynamics of the average annual and cumulative doses of the adult population of the Russian Federation after the Chernobyl nuclear power plant accident. Results and conclusions. We estimated the contribution of external and internal exposure doses accumulated during the first year after the disaster into the total doses accumulated in 1986–2016 in the population living in the areas with different levels of 137Cs activity in surface soil. The contribution of the exposure doses received during the first year after the accident into the total doses accumulated in 1986–2016 by the population of the regions with different levels of 137Cs activity in surface soil was more than 30%. The contribution of the internal exposure dose received during the first year after the accident into the total exposure dose accumulated in 1986–2016 by the population exceeded that of the external dose. We predicted the average annual and cumulative exposure doses of the population until the year 2056: in 2016, the actual average annual exposure dose for the population exceeded 1.0 mSv/year only in 19 settlements of the Bryansk Region while by 2056 the number of such settlements would be null. In 2016, the average cumulative exposure dose of the population exceeded 70 mSv in 55 settlements of the Bryansk Region, the maximum being 299 mSv. According to the forecast for the year 2056, the total number of settlements in the Bryansk Region with the average cumulative exposure dose of the population equal to or greater than 70 mSv would approach 92. All these settlements are situated only in the Bryansk Region. The maximum expected value of the average cumulative exposure dose would be 374 mSv. We estimated the contribution of the population exposure dose accumulated in 1986–2016 into the exposure dose accumulated during 70 years (a lifetime dose). The contribution of the average accumulated effective exposure dose for 1986–2016 into the dose predicted for 1986–2056 ranged 86% to 94%. This means that the major part of the lifetime dose has been already accumulated by the locals

Preliminary study and selection of CFETR in-vessel component tritium dust decontamination method in hot cell

Abstract Decontamination is a necessary and effective way of radioactive contamination reduction in the IVC (In-Vessel Component) maintenance and decommissioning process for CFETR. Plasma unstable events that occur in the reactor produces a large amount of tritium dust in the vacuum vessel. Decontamination also plays an extremely important role in reducing the radioactive pollutants diffusion, cumulative radiation dose and staff occupational exposure level, controlling radioactive effluent of nuclear facilities and enhancing remote handling equipment life and reliability and even series environmental protection problems. In this study, we carry out selection and analysis of decontaminate method for CFETR hot cell, comparing to existing mature cleaning and decontamination methods for radioactive contaminated surface, with the comprehensive consideration of the characteristics of PFC (Plasma Facing Component) pollution and the limitation of hot cell remote handling operation, analyze the adaptability and requirements of the fusion facility, selecting the most suitable cleaning method satisfied with necessary requirements for CFETR hot cell. Establishment of PFC (Plasma Facing Component) decontamination method evaluation system provides technical support for the design of hot cell remote handling cleaning device.

Interaction effects of environmental response gene polymorphisms and benzene exposure on telomere length in shoe-making workers

Benzene is a globally occurring environmental and occupational pollutant that causes leukemia. To better understand telomere length (TL) as a function of benzene toxicity, we recruited 294 shoe-making workers and 102 controls from Wenzhou, China in 2011. Biomarkers of TL, cytokinesis-block micronucleus (MN) frequency, and white blood cells (WBC) were measured. In total, 18 polymorphic sites in environmental response genes, including metabolic and DNA repair genes, were analyzed. Results indicate that benzene exposure led to a longer TL at a threshold of 32 mg/m3-year of cumulative exposure dose (CED). Furthermore, the TL was longer in members of the damaged group, when evaluated for MN frequency (P < 0.001) and reduced WBC (P < 0.001), than in those of the normal group. Workers carrying genotype TT (β = 0.32, P = 0.042) in rs3212986 of ERCC1 and genotype TC (β = 0.24, P = 0.082) in rs1051740 of mEH exon3 were associated with a longer TL as compared to the wild-type group. TA (β = −0.53, P < 0.001) in rs6413432 of CYP2E1 was associated with a shorter TL. Benzene exposure interacted with the TA type in rs6413432 (β = 0.003, 95% CI: 0, 0.006, P = 0.042) and the CC type in rs1051740 (β = 0.007, 95% CI: 0.001, 0.013, P = 0.015) after adjusting for confounding factors. Our results indicate that benzene induces an increase in TL at a threshold of CED ≥32mg/m3-year. Rs1051740, rs3212986, and rs6413432 were found to be involved in benzene-induced telomere growth; in particular, rs1051740 and rs6413432 interacted with the benzene exposure, resulting in an extended TL.

Mental Disorders and Interferon Nontreatment in Hepatitis C Virus Infection-a Population Based Cohort Study.

ObjectiveThis study investigates the association between mental disorders and interferon nontreatment in patients with chronic hepatitis C virus (HCV) infection in a large national sample. MethodsUsing the National Health Insurance Research Database of Taiwan, we conducted a nationwide population-based study. Each case was matched to five controls by age, sex, urbanization, and income. Conditional logistic regression was used to assess odds of HCV nontreatment in different mental disorders. ResultsFrom 1999 to 2013, we identified 92,970 subjects with HCV infection and 15,495 HCV cases (16.7%) had received IFN therapy. Other than chronic obstructive pulmonary disease, the medical diseases and mental disorders were significantly different between IFN and non-IFN treated HCV patients. After adjusting for medical diseases, depressive disorder and anxiety disorder was positively associated with receiving IFN therapy. Patients with schizophrenia, bipolar disorders and alcohol use disorders were significantly less likely to receive interferon. Antidepressant exposure (cumulative daily exposure or cumulative daily dose) was associated with lower odds of IFN treatment. ConclusionOur nationwide cohort study demonstrated that INF nontreatment rate was lower in certain mental disorders. Antidepressant exposure might lower the chance of receiving IFN treatment. Our results may help to identify and to overcome the obstacles for HCV treatment and further apply to DAAs regimen.

Passive Smoking Exposure in Living Environments Reduces Cognitive Function: A Prospective Cohort Study in Older Adults.

There is currently no consensus regarding the effects of passive smoking exposure on cognitive function in older adults. We evaluated 7000 permanent residents from six regions within Zhejiang Province, China, aged ≥60 years, without cognitive impairment at baseline and during follow-up examinations for two years. The Chinese version of the Mini-Mental State Examination was used to assess the participants’ cognitive function. Multivariate regression analyses were carried out to calculate the adjusted relative risks (RRs) as measures of the association between passive smoking exposure and cognitive impairment after adjusting for potential confounders. The results showed an association between passive smoking exposure in the living environment and increased risk of cognitive impairment (RR: 1.16; 95% confidence interval (CI): 1.01–1.35). No dose–response relationship between the cumulative dose of passive smoking exposure (days) and cognitive impairment was observed. The results of stratified analyses suggested a harmful effect of passive smoking exposure on cognitive function in non-smokers (RR: 1.24; 95% CI: 1.06–1.46), but not in smokers (RR: 1.11; 95% CI: 0.71–1.92). Therefore, passive smoking exposure increased the risk of cognitive impairment in older adults, especially non-smokers. More effective measures to restrict smoking in the living environment should be developed and implemented.

Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS/STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS/STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers.

Screening for Potential Biomarkers in Peripheral Blood From Miners Exposed to Radon Radiation.

In this cohort study of 144 miners, 72 miners worked underground (the study group) and 72 miners worked aboveground (the control group). Based on questionnaire data and of radon concentration measurements, the cumulative radon exposure dose was calculated for each miner using the parameters recommended in International Commission on Radiological Protection Publication 137. Hematological parameters such as lymphocyte count (LYM) and neutrophil count (NE) were assessed, cell cycle phases and regulatory proteins were detected by flow cytometry, and microRNA (miRNA) microarray screening and real-time polymerase chain reaction (PCR) were used to detect miRNAs in plasma. The interrelationships between various potential biomarkers were analyzed using bioinformatics and statistical methods. The mean cumulative exposure dose of underground miners and controls was 982 and 48 mSv, respectively. Hematological parameters (such as LYM and NE) were significantly lower in the underground group. Cyclin-dependent kinase (CDK)-2, CDK4, CDK6, CyclinA2, CyclinD1, and CyclinE1 were significantly higher in the underground group. MicroRNA microarray screening showed that 5 miRNAs were downregulated (fold-change >2) in the underground group. The real-time PCR detection results of miR-19a, miR-30e, miR-335, and miR-451a were consistent with the screening results. LYM, NE, CDK2, CDK4, CDK6, Cyclin A2, Cyclin D1, Cyclin E1, miR-19a, miR-30e, miR-335, and miR451a are potential biomarkers of radon radiation damage.