Cumulative Exposure Dose Research Articles

Effects of polycyclic aromatic hydrocarbon exposure and miRNA variations on peripheral blood leukocyte DNA telomere length: A cross-sectional study in Henan Province, China

Telomeres play a major role in human aging and disease, especially in most cancers. Telomere length was shortened in workers exposed to polycyclic aromatic hydrocarbons (PAHs) and influenced by individual genetic variations in telomere-binding proteins. MicroRNAs (miRNAs) can affect the progress of messenger RNA (mRNA) transcription; however, whether polymorphisms in miRNA can act on the telomere length is still unknown. Therefore, we aimed to explore the relationships between telomere damage and genetic polymorphisms in miRNA or environmental exposure. A total of 544 coke oven workers and 238 healthy controls were recruited. After collecting peripheral blood and extracting the genomic DNA of the study subjects, the telomere length (TL) in their leucocytes was detected by a real-time quantitative polymerase chain reaction (PCR), and polymorphisms in miRNAs were genotyped using the flight mass spectrometry technique. The concentrations of the four urine OH-PAHs were determined by high performance liquid chromatography (HPLC), and the Soxhlet extraction method was used to detect the concentration of coke oven emissions (COEs) in the air. We found that the peripheral blood leucocyte DNA TL was significantly shorter in the exposure group (0.75; 0.51, 1.08) than that in the control group (1.05; 0.76, 1.44) (Z = 7.692, P < 0.001). The total cumulative exposure dose (CED), 1-hydroxypyrene, 2-hydroxynaphthalene, and 3-hydroxyphenanthrene were significantly negatively correlated with TL (r = −0.307, P < 0.001; r = −0.212, P < 0.001; r = −0.110, P = 0.025; r = −0.251, P < 0.001, respectively). MiR-145 rs353291 GG, miR-30a rs2222722 CT/CC, and miR-197 rs1889470 AA could protect the telomere end in the exposed workers (P < 0.05). The interaction between miR-197 rs1889470 and the CED had an effect on TL (β = 0.066, P = 0.034). This is the first study to evaluate gene–environmental interactions for miRNA polymorphisms and PAH exposure in coke oven workers.

PGC1α activation by pterostilbene ameliorates acute doxorubicin cardiotoxicity by reducing oxidative stress via enhancing AMPK and SIRT1 cascades.

Doxorubicin (DOX) is a widely used and potent anticancer agent, but DOX dose-dependently induced cardiotoxicity greatly limits its use in clinic. Pterostilbene, a natural analog of resveratrol, is a known antioxidant and exerts myocardial protection. The present study explored the action and detailed mechanism of pterostilbene on DOX-treated cardiomyocytes. We investigated the effects of pterostilbene on established acute DOX-induced cardiotoxicity models in both H9c2 cells treated with 1 μM DOX and C57BL/6 mice with DOX (20 mg/kg cumulative dose) exposure. Pterostilbene markedly alleviated the DOX exposure-induced acute myocardial injury. Both in vitro and in vivo studies revealed that pterostilbene inhibited the acute DOX exposure-caused oxidative stress and mitochondrial morphological disorder via the PGC1α upregulation through activating AMPK and via PGC1α deacetylation through enhancing SIRT1. However, these effects were partially reversed by knockdown of AMPK or SIRT1 in vitro and treatment of Compound C (AMPK inhibitor) or EX527 (SIRT1 inhibitor) in vivo. Our results indicate that pterostilbene protects cardiomyocytes from acute DOX exposure-induced oxidative stress and mitochondrial damage via PGC1α upregulation and deacetylation through activating AMPK and SIRT1 cascades.

Membrane ageing in full-scale water treatment plants

Membrane filtration is a rapidly expanding choice for drinking water treatment. Unfortunately, there is limited data on long-term changes in the membranes’ performance as they age. The present research investigated changes in performance factors as well as chemical characteristics for hollow-fibre ultrafiltration membranes that ranged in age from 8 full-scale drinking water treatment plants. Membranes were harvested by plant operators regularly and analyzed using standardized laboratory tests. Approximately half of the membranes were a new PVDF-based chemistry. These were observed to have insignificant changes in performance factors and chemical characteristics since their beginning of operation. However, because these membranes were newer, only data for the first 5 years of operation was available. The other half of the membranes, with an older PVDF-based chemistry, were observed to have stable behaviour until approximately 5 years of operation; after this time, performance factors and chemical characteristics of the membranes began to change significantly. For these membranes, the clean water resistance and fouling rate increased after 5 years of operation. The mechanical properties of these membranes also deteriorated after 5 years of operation, suggesting that their susceptibility to breach is higher after prolonged use. These changes in performance factors paralleled, and were possibly caused by, the removal of hydrophilic additives from the membrane material. Clean water resistance was identified as a good benchmark for all the parameters studied, a finding that is useful for water treatment facilities in quickly assessing the status of their membranes. Finally, although cumulative exposure dose (C*t) was not used as a metric of membrane age, we observed that when higher doses of hypochlorite were applied, all metrics changed faster than expected based only on years of operation. Therefore, limiting the magnitude of the cumulative hypochlorite dose is essential in managing membrane deterioration. This research illuminates the knowledge gap between bench-scale ageing studies and operational water treatment plants.

Exposure-Response Relationship and Doubling Risk Doses-A Systematic Review of Occupational Workload and Osteoarthritis of the Hip.

In this review, we critically evaluated the evidence of exposure–response relationships between occupational workload and the risk of hip osteoarthritis. The existing evidence was evaluated in order for us to extrapolate possible doubling risk doses for hip osteoarthritis. Comprehensive searches for epidemiological studies of hip osteoarthritis and occupational workload were performed in literature databases (PubMed, EMBASE, Cochrane Work and Google Scholar) and recent reviews up to February 2019. In total, 85 papers met the preliminary inclusion criteria, and 10 studies indicating an exposure-response relationship between occupational workload and hip osteoarthritis were identified. All studies were assessed on the basis of their study design, defined quality scores and relevant confounders considered. An exposure–response relationship between heavy lifting and the risk of hip osteoarthritis is consistently observed among the male populations but not among the female populations. We quantified the doubling risk doses in two studies in which both an exposure–response relationship and cumulative exposure doses were stated. These two studies provided the highest quality level of all studies published to date. The estimated doubling risk doses in these two studies lie between 14,761 and 18,550 tons (daily lifting 2.2–2.8 tons, 220 days/year for 30 years). These results can be used for workplace interventions to prevent hip osteoarthritis.

Abstract 304: Pgc1a Activation by Pterostilbene Ameliorates Acute Doxorubicin Cardiotoxicity via Reducing Mitochondrial Oxidative Stress Through Enhancing Ampk and Sirt1 Cascades

Background: Doxorubicin (DOX) is a widely used and potent anticancer agent, but DOX dose-dependently induced cardiotoxicity greatly limits its use in clinic. Pterostilbene, a natural analog of resveratrol, is a known antioxidant and exerts myocardial protection. The present study explored the actions and detailed mechanisms of pterostilbene on DOX-treated cardiomyocytes. Experimental Approach: We investigated the effects of pterostilbene on established acute DOX-induced cardiotoxicity models in both H9c2 cells treated with 1 μM DOX and C57BL/6 mice with DOX (20 mg/kg cumulative dose) exposure. Cell viability, ATP content, oxidative parameters, transmission electron microscopy, western blot analyses were respective performed. AMPK and SIRT1 siRNA, Compound C and EX527 treatment were further conducted to elucidate the underlying mechanism about the involvement of AMPK, SIRT1 and PGC1α cascades. Key Results: Pterostilbene markedly upregulated the cell viability and ATP content in DOX-treated H9c2 cells. Both in vitro and in vivo studies revealed that pterostilbene inhibited the acute DOX exposure-caused oxidative stress and mitochondrial morphological disorder via the PGC1α upregulation through activating AMPK and via PGC1α deacetylation through enhancing SIRT1. However, these effects were partially reversed by knockdown of AMPK or SIRT1 in vitro and treatment of Compound C or EX527 in vivo . Conclusion and Implications: Our results indicate that pterostilbene protects cardiomyocytes from acute DOX exposure-induced oxidative stress and mitochondrial damage via PGC1α upregulation and deacetylation through activating AMPK and SIRT1 cascades.

MON-194 RECURRENCE OF MPO VASCULITIS IN THE IMMEDIATE POST TRANSPLANT PERIOD

49 year old male was diagnosed with MPO vasculitis and was treated with steroids and cyclophosphamide during induction phase and azathioprine during maintenance phase. During the maintenance phase he suffered relapse of vasculitis and hence was reinduced with cyclophosphamide. His renal function continued to deteriorate and he was started on dialysis. Post treatment of relapse and during dialysis his ANCA titres remained positive between 40 to 60 units. However clinically he appeared to be in remission. He proceeded to have a living related donor transplant. He received standard induction transplants immunosuppression. Immediate post-transplant he was passing good volumes of urine and his creatinine was rapidly falling. However Day 5, he developed acute graft dysfunction with hypertension and oliguria. He underwent a renal biopsy which didn’t show any evidence of rejection but revealed crescentic Glomerulonephritis with negative immunofluorescence consistent with pauci immune rapidly progressive glomerulonephritis. Subsequently MPO titres were done, which was strongly positive. Plasma exchange was performed along with methyl prednisone and patient was given rituximab for relapse of ANCA vasculitis. His creatinine significantly improved over a period of 1 month and ANCA titres became negative. Discussion: Pauci Immune Glomerulonephritis is the most common cause of rapidly progressive glomerulonephritis. Standard treatment for ANCA associated vasculitis consists of combined use of cyclophosphamide and steroids. Although this treatment had dramatically changed the prognosis, 20% of patients with AAV will develop ESRD during their lifetime. Kidney Transplantation improves both the life expectancy and quality of life in patients with ESRD. For patients with ANCA vasculitis, both the KDIGO and Canadian society of transplantation recommend that AAV patients should be in clinical remission for 1 year prior to proceeding for transplantation. ANCA positivity is not a contraindication for transplantation, however it has been reported that patients with ANCA positivity more likely to develop severe vasculopathy in graft and recurrence of vasculitis in allograft. Rate of recurrence of ANCA vasculitis in the post transplantation period is variable ranging from 1.6%-17.3%. The higher rate of recurrence was reported in patients receiving prednisone, cyclosporine and azathioprine for immunosuppression, whereas with the current tacrolimus and mycophenolate regimens, the rate of relapse in much lower. Average time to recurrence in the above studies was 20 months to 68 months post transplant. Our patient had recurrence of vasculitis day 5 after transplantation despite aggressive induction immunosuppression. There is no consensus on treatment on ANCA vasculitis post transplantation. Most reports have used plasma exchange, induction with cyclophosphamide and maintenance with Mycophenolate. Our patient had a cumulative dose exposure of cyclophosphamide of 6000mg. A decision was made to treat with Rituximab instead of cyclophosphamide to reduce the risk of long term complication especially malignancies associated with cyclophosphamide, in addition to plasma exchange and steroids. His post-transplant immunosuppression of tacrolimus, mycophenolate was continued. This is the first case of recurrence of MPO vasculitis in the immediate transplant period within 5 days.

The changing burden of long-term health outcomes in survivors of childhood acute lymphoblastic leukaemia: a retrospective analysis of the St Jude Lifetime Cohort Study

Treatment for childhood acute lymphoblastic leukemia has evolved over the past five decades, with moderation of traditional chemotherapy and radiotherapy and the introduction of targeted immune-based and cellular-based therapies. The affect of these changes on late health outcomes has not been assessed. Using data from the The St Jude Lifetime (SJLIFE) Cohort, we aimed to characterise the magnitude of morbidity and patterns of late health outcomes among survivors of childhood acute lymphoblastic leukaemia treated over time. The St Jude Lifetime (SJLIFE) Cohort is a retrospective cohort study with prospective follow-up and ongoing data accrual designed to facilitate longitudinal, clinically-based assessment of health outcomes among survivors of paediatric malignancies. 980 survivors included in this analysis were diagnosed with paediatric acute lymphoblastic leukaemia at St Jude Children's Research Hospital (SJCRH) between Aug 28, 1963, and July 19, 2003, were aged 18 years old and older at enrolment, had a minimum follow-up of 10 years after diagnosis, and completed an initial on-campus SJLIFE assessment as of data cutoff (June 30, 2015). 272 community control participants, matched to survivors on 5-year age blocks in each sex, were recruited for comparison. Cumulative chemotherapy and radiation dose exposures and major medical events during and after therapy were retrieved from the medical records of the survivors. History or physical examination, laboratory analysis, physical fitness, and neurocognitive testing were done. Health conditions were graded according to a modified version of the Common Terminology Criteria for Adverse Events. Neurocognitive domains of attention (Trial Making Test Part A and Conner's Continuous Performance Test-II) and executive function (Trail Making Test Part B, Controlled Oral Word Association Test, and Wechsler Adult Intelligence Scale-III Digit Span Test Backward) were measured and age-adjusted Z scores were calculated. Mean cumulative count was used to calculate the age-standardised cumulative burden of health conditions over time. This cohort study is registered at ClinicalTrials.gov, number NCT00760656. 980 survivors of acute lymphoblastic leukaemia (50% women, median age at diagnosis 5 years [IQR 3·1-9·1 years], and median time from diagnosis of 30·0 years [22·7-36·3]) had a median age of 35·8 years (29·4-42·9) at assessment compared with 35·1 years (28·7-42·6) for 272 controls. Survivors had significantly more growth hormone deficiency, hypogonadism, and neuropathy than controls. By age 30 years, survivors of acute lymphoblastic leukaemia had, on average, 5·4 (95% CI 5·1-5·8) grade 1-4 health conditions, including 3·2 (2·9-3·4) grade 2-4 health conditions, compared with 2·0 (CI 1·7-2·2) grade 1-4 and 1·2 (1·03-1·4) grade 2-4 health conditions among controls. The cumulative burden of grade 2-4 health conditions involved multiple organ systems for survivors treated on protocols between 1962-91, but after elimination of cranial radiotherapy for children with acute lymphoblastic leukaemia, conditions now predominately include musculoskeletal and endocrine disorders for survivors on protocols between 1991-2007. Although changes in paediatric acute lymphoblastic leukaemia treatment protocols have improved overall survival, the burden of late morbidity remains high for these patients. We show that the pattern of late toxic effects has markedly changed over time, with survivors having a reduction in health conditions that are immediately life-threatening, however, maintaining health status and quality of life for survivors of paediatric acute lymphoblastic leukaemia requires continued medical surveillance, counselling, and lifestyle modifications. US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Cumulative radiation exposure dose of diagnostic imaging studies in breast cancer patients

Cumulative radiation exposure dose of diagnostic imaging studies in breast cancer patients

Cancer incidence and mortality associated with non-occupational and low dose exposure to Libby vermiculite in Minnesota

BackgroundA vermiculite processing plant in a Minneapolis, Minnesota neighborhood utilized asbestos-containing ore from Libby, Montana from the late 1930's until 1989. Multiple pathways of exposure to Libby asbestos were characterized in a cohort of over 6000 plant workers and residents living near the plant. ObjectiveWe conducted a cohort linkage study to assess the impact of cumulative low dose exposure and the role of occupational history on asbestos-related mortality and cancer morbidity among cohort members residing near a vermiculite plant. MethodsCohort members alive in 1988 (n = 5848) were linked to the Minnesota Cancer Surveillance System to identify incident cases of mesothelioma, lung cancer, and all-cancer diagnosed from 1988 to 2010. Proportional incidence ratios (PIRs) were calculated for mesothelioma and lung cancer. Vital status and cause of death were ascertained from Minnesota vital records and the National Death Index (1988–2011). Mortality rates of the cohort (2001–2011) for asbestos-related outcomes were compared to the Minnesota population to estimate standardized mortality ratios (SMRs) and stratified by gender, exposure, and occupational history categories. ResultsWe identified seven cases of mesothelioma, with elevated incidence only in females (PIR = 11.76, 95% CI: 3.17, 30.12). Lung cancer was elevated in both genders: PIR = 1.54 (95% CI: 1.19, 2.0) in males and 1.62 (95% CI: 1.21, 2.12) in females. We found elevated mortality from COPD, lung cancer, and mesothelioma among females (SMR for mesothelioma in females = 18.97, CI: 3.91, 55.45), among the 546 deaths identified. All four deaths from mesothelioma occurred in the >75th percentile of exposure (>0.0156 fiber/cc x months). The SMR for lung cancer and all respiratory cancer was elevated even after controlling for occupation. ConclusionsCommunity exposure to Libby amphibole asbestos from a vermiculite processing plant is associated with increased risk of COPD, lung cancer and mesothelioma incidence and mortality, most notably among females, and is likely to remain a public health issue for years to come.

Chronic long-term exposure to cadmium air pollution and breast cancer risk in the French E3N cohort.

Cadmium, due to its estrogen-like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case-control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long-term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER-/ER+] and progesterone receptor negative/positive [PR-/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System-based metric, which included subject's residence-to-cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER- (ORQ5 vs. Q1 = 0.63; 95% CI: 0.41-0.95, ptrend = 0.043) and for ER-/PR- breast tumors (ORQ4 vs. Q1 = 0.62; 95% CI: 0.40-0.95, ORQ5 vs. Q1 = 0.68; 95% CI: 0.42-1.07, ptrend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER- and ER-/PR- breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations.

Enteral iron supplementation, red blood cell transfusion, and risk of bronchopulmonary dysplasia in very-low-birth-weight infants.

Enteral iron supplementation and RBC transfusions are routinely administered to very-low-birth-weight (VLBW) infants, although the potential risks of these exposures have not been adequately quantified. This study evaluated the association between the cumulative dose of enteral iron supplementation, total volume of RBCs transfused, and risk of bronchopulmonary dysplasia (BPD) in VLBW infants. Retrospective, multicenter observational cohort study in Atlanta, Georgia. Cumulative supplemental enteral iron exposure and total volume of RBCs transfused were measured until the age at assessment of BPD. Multivariable generalized linear models were used to control for confounding, and the reliability of the factors was assessed in 1000 bootstrap models. A total of 598 VLBW infants were studied. In multivariable analyses, a greater cumulative dose of supplemental enteral iron exposure was associated with an increased risk of BPD (adjusted relative risk per 50-mg increase, 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.002). Similarly, a greater volume of RBCs transfused was associated with a higher risk of BPD (adjusted relative risk per 20-mL increase, 1.05; 95% CI, 1.02-1.07; p < 0.001). Both factors were reliably associated with BPD (>50%). Volume of RBCs transfused was similar to gestational age in reliability as a risk factor for BPD (present in 100% of models) and was more reliable than mechanical ventilation at 1 week of age. The cumulative dose of supplemental enteral iron exposure and total volume of RBC transfusion are both independently associated with an increased risk of BPD in VLBW infants.

Chronic low dose exposure of hospital workers to ionizing radiation leads to increased micronuclei frequency and reduced antioxidants in their peripheral blood lymphocytes

Purpose: The regular low dose occupational exposure to ionizing radiation may induce deleterious health effects, which may be of particular interest to medical radiation workers who daily handle X-ray machines. Human peripheral blood lymphocytes are able to retain the signature of radiation-induced DNA damage, therefore, the present study was undertaken to investigate the DNA damage and antioxidants status in hospital workers occupationally exposed to low doses of X-rays.Materials and methods: The peripheral blood lymphocytes of the occupationally exposed and control groups matched for age, gender, tobacco usage, and alcohol consumption were cultured and micronuclei frequency was determined. Activities of antioxidant enzymes and lipid peroxidation were also estimated in their plasma.Results: The micronuclei frequency in the occupationally exposed group (n = 33), increased significantly (p < .0001) followed by reduced glutathione-s-transferase (p < .01) and catalase (p < .001) activities, and increased lipid peroxidation (p < .05) when compared to the control group (n = 33). Occupational exposure resulted in an effective dose ranging between 3.14 to 144.5 mSv (40.88 ± 39.86mSv) depending on the employment duration of 3–29 years (10.33 ± 7.05 years). A correlation between the micronuclei frequency (p < .05) and catalase activity (p < .05) existed in the occupationally exposed individuals depending on the smoking habit, age, duration of employment, cumulative exposure dose and number of patients handled per day.Conclusions: We have observed that protracted low dose exposure to ionizing radiation is an inevitable occupational hazard leading to persistence of oxidative stress and increased genomic instability in the radiological technicians depending on the time spent with X-rays, cumulative dose received and the number of patients handled daily raising the risk of cancer development.

Relative telomere length and gene expression of shelterin complex proteins among vinyl chloride monomer-exposed workers in China.

Vinyl chloride monomer (VCM) is a confirmed carcinogen. The effects of VCM on telomeres and the gene expression of telomere complex proteins, shelterin, have not been well studied but could be of potential relevance to the carcinogenic mechanism of VCM and the health surveillance of VCM-exposed workers. A group of 241 VCM-exposed workers and 101 internal controls from the same plant in Shandong, China were recruited and quantitative polymerase chain reaction was preformed to measure relative telomere length (RTL) and gene expression of shelterin proteins. VCM cumulative exposure dose (CED) was estimated for the exposed workers. The differences in RTL and gene expression between groups were compared by Wald test fitted with robust regression. Shorter RTL was observed in VCM-exposed workers than in the controls (P < 0.001) and was related to CED of VCM. Shortened RTL was also significantly related to increasing age (P = 0.012) and high blood pressure (P = 0.056). Levels of gene expression of shelterin components in exposed workers were all lower than in controls except increased TIN2 expression, and the gene expression differences in TIN2 and POT1 among exposed and control groups were significant (P = 0.014 for TIN2 and P < 0.001 for POT1, respectively). VCM exposure is found associated with altered telomere length and gene expression of shelterin components. This provides new insights into the potential carcinogenic mechanisms of VCM and could be helpful for the health surveillance for VCM-exposed workers. Environ. Mol. Mutagen. 60:361-367, 2019. © 2018 Wiley Periodicals, Inc.

Assessment of Level of Radiation Leakage at Certain Scientific Stores

Background: Radiation is a radiation dose rate at a specified location which is generated by any combination of natural and artificial (man-made) ionizing radiation sources. Background radiation varies with location and time. The global average exposure of humans to ionizing radiation is about 2.4 – 3mSv (0.0024-0.003Sv) per year. Objective: To detect, and calculate the total cumulative dose of radiation exposure in the center of the store and outside by moving the detector

Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy: Population-Based Nested Case-Control Study.

Background and ObjectiveTendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure.MethodsThe UK Health Improvement Network primary care database was used to perform a nested case–control study measuring the association between fluoroquinolone exposure and tendon rupture. Adults with tendon rupture were matched on age, sex, general practice and calendar time to four controls selected from a cohort prescribed systemic fluoroquinolone or co-amoxiclav antibiotics. The relative and absolute risk of tendon rupture with fluoroquinolone exposure was calculated.ResultsCurrent fluoroquinolone exposure was associated with an increased risk of any tendon rupture (adjusted incidence rate ratio [aIRR] 1.61, 95% CI 1.25–2.09) and Achilles tendon rupture (aIRR 3.14, 95% CI 2.11–4.65) that persisted for 60 days. Risk increased with cumulative exposure and was greatest when co-prescribed with oral corticosteroids (aIRR 19.36, 95% CI 7.78–48.19 for Achilles tendon rupture). The adjusted rate difference (aRD) with fluoroquinolone exposure was 2.9 and 2.1 per 10,000 patients for any and Achilles tendon rupture, respectively, and was greatest in people aged ≥ 60 years prescribed concomitant oral corticosteroid therapy (aDR 19.6 for any tendon and 6.6 Achilles tendon rupture per 10,000). No association was seen with co-amoxiclav or statin exposure, or with biceps or other tendon ruptures.ConclusionsRisk of tendon rupture with fluoroquinolones depends on timing, cumulative dose and concomitant exposure to oral corticosteroids. Absolute risk significantly varied by age and concomitant corticosteroid exposure, affecting elderly patients the greatest.Electronic supplementary materialThe online version of this article (10.1007/s40261-018-0729-y) contains supplementary material, which is available to authorized users.

Decreased blood cell counts were not observed in cattle living in the "difficult-to-return zone" of the Fukushima nuclear accident.

White blood cells, especially lymphocytes, are susceptible to radiation exposure. In the present study, red blood cell, total white blood cell, and lymphocyte counts were repeatedly measured in cattle living on three farms located in the “difficult‐to‐return zone” of the Fukushima nuclear accident, and compared with two control groups from unaffected areas. Blood cell counts differed significantly between the two control groups, although almost all the values fell within the normal range. The blood cell counts of the cattle in the “difficult‐to‐return zone” varied across sampling times even on the same farms, being sometimes higher or lower than either of the two control groups. However, neither a statistically significant decrease in blood cell counts nor an increase in the rate of cattle with extremely low blood cell counts was observed overall. The estimated cumulative exposure dose for the cattle on the most contaminated farm was within a range of 500–1000 mSv, exceeding the threshold for the lymphopenia. Because of the low dose rate on these farms, potential radiation damages would have been repaired and have not accumulated enough to cause deterministic effects.

Radiation exposure of very-low-birth-weight infants in neonatal intensive care units in Korea

To our knowledge, no study has reported the radiation doses of neonates admitted to neonatal intensive care units (NICUs) in Korea. Therefore, we evaluated the radiation frequency and dose of radiation performed in NICUs using mobile X-ray machines. We retrospectively analyzed the number of radiographs and doses among 290 very low-birth-weight infants (VLBWIs) admitted at our hospital between 2011 and 2016. We compared X-ray frequencies and radiation doses according to clinical characteristics and morbidities. The entrance surface doses (ESDs) were calculated using the non-dosimeter dosimetry formula. The median number of radiographs per infant was 26, and about 25% neonates had over 50 radiographs. The number of radiographs taken was higher for infants with low-birth-weight (LBW), respiratory distress syndrome, bronchopulmonary dysplasia, and longer central venous catheterization duration (p &lt; 0.001 for all). The cumulative ESD was 0.18 to 9.89 mGy, and the ESD per radiograph was 0.049 to 0.069 mGy. The LBW and the more severe the neonates’ condition, the greater was the radiation exposure. It is difficult to reduce the number of radiographic examinations, but the quality of examinations must be improved without compromising patient care. Additional studies are needed to minimize the cumulative exposure dose and achieve optimal image quality.

Chloroethene. Documentation of proposed values of occupational exposure limits (OELs)

Chloroethene. Documentation of proposed values of occupational exposure limits (OELs)

Evaluation of Gentamicin Exposure in the Neonatal Intensive Care Unit and Hearing Function at Discharge

To characterize the association between gentamicin dosing, duration of treatment, and ototoxicity in hospitalized infants. This retrospective cohort study conducted at 330 neonatal intensive care units (2002-2014) included inborn infants exposed to gentamicin with available hearing screen results, and excluded infants with incomplete dosing data and major congenital anomalies. Our primary outcome was the final hearing screen result performed during hospitalization: abnormal (failed or referred for further testing in one or both ears) or normal (bilateral passed). The 4 measures of gentamicin exposure were highest daily dose, average daily dose, cumulative dose, and cumulative duration of exposure. We fitted separate multivariable logistic regression models adjusted for demographics, comorbidities, and other clinical events. A total of 84 808 infants met inclusion/exclusion criteria; median (25th, 75th percentile) gestational age and birth weight were 35 weeks (33, 38) and 2480 g (1890, 3184), respectively. Failed hearing screens occurred in 3238 (3.8%) infants; failed screens were more likely in infants of lower gestational age and birth weight, who had longer hospital lengths of stay, higher rates of morbidities, and were small for gestational age. Median highest daily dose, average daily dose, and cumulative dose were 4.0 mg/kg/day (3.0, 4.0), 3.8 mg/kg/day (3.0, 4.0), and 12.1 mg/kg (9.1, 20.5), respectively. Median cumulative duration of exposure was 3 days (3, 6). In adjusted analysis, gentamicin dose and duration of therapy were not associated with hearing screen failure. Gentamicin dosing and duration of treatment were not associated with increased odds of failed hearing screen at the time of discharge from initial neonatal intensive care unit stay.

Estimation of formaldehyde occupational exposure limit based on genetic damage in some Iranian exposed workers using benchmark dose method.

The present study evaluated an occupational exposure level for formaldehyde employing benchmark dose (BMD) approach. Dose-response relationship was determined by utilizing cumulative occupational exposure dose and DNA damage. Based on this goal, outcome of comet assay for some Iranian exposed people in occupational exposure individuals was used. In order to assess formaldehyde exposure, 53 occupationally exposed individuals selected from four melamine tableware workshops and 34 unexposed subjects as a control group were examined. The occupational exposure dose was carried out according to the NIOSH-3500 method, and the DNA damage was obtained by employing comet assay in peripheral blood cells. EPA Benchmark Dose Software was employed for calculating BMD and BMDL. Cumulative exposure dose of formaldehyde was between of 2.4 and 1972mg. According to the findings of the current study, the induction of DNA damage in the exposed persons was increased tail length and tail moment (p < 0.001), when compared to controls. Finally, an acceptable dose-response relationship was obtained in three-category information between formaldehyde cumulative exposure doses and genetic toxicity. BMDL was 0.034mg/m3 (0.028ppm), corresponding to genetic damage of peripheral blood cells. It can be concluded that the occupational permissible limit in Iranian people could be at levels lower than OSHA standards.