Non-exposed Reference Research Articles

Genetic And Environmental Associations Of Nonspecific Chromosomal Aberrations.

Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation are believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study (GWAS) in healthy individuals in relation to occupational and smoking-related exposure compared to non-exposed referents. The associations (at p<10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

Evaluate the Work-Related Exposure of Vanadium on Scalp Hair Samples of Outdoor and Administrative Workers of Oil Drilling Field: Related Health Risks.

Petrochemical facilities, including oil well drilling, are discharging resources of extensive noxious waste into the environment. The workers in different sections might be exposed to vanadium (V) through different routes (groundwater and soil), which is linked with extensive physiological disorders, hypertension, respiratory disorders, anemia, skin, and gastrointestinal disorders. This study determined the contents of V in a biological sample (scalp hair) of workers of different categories (outdoor and office workers) in an oil drilling field in Sindh, Pakistan. The environmental samples, groundwater, bottled mineral water, and soil samples were also analyzed for V. For comparative purposes, the scalp hair of age-matched male subjects residing in domestic areas of Hyderabad city, Pakistan, was also analyzed. Generally, the concentrations of V in groundwater near the oil drilling field and drilled soil illustrated significant variations. The results show that the vanadium concentration in the scalp hair of non-exposed referents (controls) and office workers (exposed referents) was 62% and 45% lower than those observed for outdoor drilling and cleaning mud workers. It was observed that high exposure to V in outdoor workers might be linked with different physiological disorders such as anemia, eye problems, and bronchial disorders.

Low Household Income Status and Death from Pneumonia in People with Type 2 Diabetes Mellitus: A Nationwide Study.

We explored the risk of death from pneumonia according to cumulative duration in low household income state (LHIS) among adults with type 2 diabetes mellitus (T2DM). Using Korean National Health Insurance Service data (2002 to 2018), the hazards of mortality from pneumonia were analyzed according to duration in LHIS (being registered to Medical Aid) during the 5 years before baseline (0, 1-4, and 5 years) among adults with T2DM who underwent health examinations between 2009 and 2012 (n=2,503,581). Hazards of outcomes were also compared in six groups categorized by insulin use and duration in LHIS. During a median 7.18 years, 12,245 deaths from pneumonia occurred. Individuals who had been exposed to LHIS had higher hazards of death from pneumonia in a dose-response manner (hazard ratio [HR], 1.726; 95% confidence interval [CI], 1.568 to 1.899 and HR, 4.686; 95% CI, 3.948 to 5.562 in those exposed for 1-4 and 5 years, respectively) compared to the non-exposed reference. Insulin users exposed for 5 years to LHIS exhibited the highest outcome hazard among six groups categorized by insulin use and duration in LHIS. Among adults with T2DM, cumulative duration in LHIS may predict increased risks of mortality from pneumonia in a graded dose-response manner. Insulin users with the longest duration in LHIS might be the group most vulnerable to death from pneumonia among adults with T2DM.

Which risk factors determine cartilage thickness and composition change in radiographically normal knees? – Data from the Osteoarthritis Initiative

ObjectiveTherapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees “at risk” of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations. Design755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were “at risk”, whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n ​= ​59/52). Subregion values were used to compute location-independent change scores. ResultsIn KLG0 knees “at risk”, the femorotibial cartilage thinning score (−634 ​± ​516 ​μm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p ​< ​0.01; Cohen D −0.27) than the thinning score in “non-exposed” knees (−501 ​± ​319 ​μm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p ​≥ ​0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden's nodes, repetitive knee bending were not significantly associated with cartilage thinning (r2<1%), with only knee pain reaching statistical significance. ConclusionsKnees “at risk” of incident knee OA displayed greater cartilage thinning scores than those “non-exposed”. Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors.

The prevalence of hoarseness among health care professionals: time trends and effect of remediation in working conditions in 2007–2018

PurposeThe purpose of this study was to investigate time trends in the prevalence of hoarseness among health care professionals in primary health care units (PHC) and in hospitals from 2007 to 2018. Moreover, purpose was to discover potential indoor environmental quality (IEQ) risk factors as well as to determine the effect of the remediation of the indoor air problems on the prevalence of hoarseness.MethodsThe health status was collected from all employees in these units/hospitals (N = 1564/1199) with questionnaires and the follow-ups were carried out as an open cohort. Based on building condition inspections, buildings were classified to be an “exposed” or “reference” buildings by third-party experts. The before and after remediation results were compared to reference buildings.ResultsDuring follow-up, hoarseness has not increased in those PHC units with good IEQ. In the pilot study, the prevalence of hoarseness in non-exposed reference building was 5.9%, and it stayed approximately at the same level throughout the follow-up. Whereas in buildings with an IEQ problem the prevalence of hoarseness varied between 16.2 and 36.1% and it decreased to 11.4% after the remediations. In a large hospital with severe IEQ problems, the prevalence of hoarseness was 39.1%, and in hospital buildings with a milder exposure 23.3%. The most important risk factors for hoarseness were asthma, allergic rhinitis and IEQ problems.ConclusionA good indoor environment and the remediation of damaged buildings seem to promote a better condition of the voice in health care workers.

Association Between Traumatic Brain Injury and Increased Risk of Stroke: A Systematic Review and Meta-analysis.

To determine whether exposure to traumatic brain injury (TBI) is associated with increased risk of stroke in adults compared with referents not exposed to TBI, and to understand whether an association exists throughout the spectrum of injury severity, whether it differs between the acute and chronic phases after TBI, and whether the association is greater with hemorrhagic compared with ischemic stroke after TBI. A database search was conducted on January 22, 2021. Searches were run in MEDLINE (1946 to present), Embase (1988 to present), Evidence-Based Medicine Reviews (various dates), Scopus (1970 to present), and Web of Science (1975 to present). Observational studies that quantified the association of stroke after TBI compared with referents without TBI were included. Three coauthors independently reviewed titles and abstracts to determine study eligibility. Study characteristics were extracted independently by 2 coauthors who followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and study quality was assessed independently by 2 coauthors who used the Newcastle-Ottawa Scale. Random-effects meta-analyses were performed. The primary exposure was TBI of any severity, and the primary outcome was stroke of any kind. Subgroup analysis was performed to assess heterogeneity associated with severity of TBI, type of stroke, and time from TBI to stroke. A total of 64 full-text articles were reviewed, and data were extracted from 8 cohort studies (N = 619 992 individuals exposed to TBI along with nonexposed referents). A significant overall association was found with TBI and stroke (hazard ratio, 2.06; 95% CI, 1.28-3.32). Significant subgroup differences were found with a smaller risk of ischemic stroke compared with stroke of all types (P < .001, I² = 93.9%). TBI, regardless of injury severity, was associated with a higher risk of stroke. To improve secondary stroke prevention strategies, future studies should classify TBI severity and type of stroke more precisely and determine long-term risk.

Late effects of high-dose methotrexate treatment in childhood cancer survivors\u2014a systematic review

BackgroundHigh-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m2 body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking.MethodWe conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262).ResultsWe included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision.ConclusionsCCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX.

Reaction Times among Batik Workers: The Influence of Gender and Occupational Lead Exposure.

(1) Background: Neglected occupational health and safety aspects in batik industries cause their workers to have an increased risk of lead exposure. The effect of occupational lead exposure on neurocognitive performance is inconclusive. Therefore, we conducted an observational study to examine the difference in simple reaction time between lead-exposed batik workers and non-exposed referents. (2) Methods: This cross-sectional study was conducted in seven batik enterprises in Lendah District, Indonesia, excluding workers with medical conditions impairing reaction time. Simple reaction time tests were conducted using an online tool. Two-way model ANCOVAs examined interactions between gender and job types on the mean differences in reaction time. (3) Results: After controlling for age and body mass index, we observed longer reaction times among lead-exposed batik workers than non-exposed referents with an adjusted mean difference of 0.19 (95% CI: 0.016–0.368) seconds. A more prominent detrimental effect of lead exposure on reaction time among female workers than among male workers was observed. (4) Conclusions: Our results suggest that occupational lead exposure could contribute to longer reaction time, notably among female workers. Thus, occupational health and safety precautions are vital to protect batik workers and preserve their important contributions to cultural heritage.

A Review of Environmental Risk Factors for African Swine Fever in European Wild Boar.

A detailed understanding of environmental risk factors for African swine fever (ASF) in wild boar will be not only essential for risk assessments but also for timely and spatially informed allocation of resources in order to manage wild boar-targeted ASF control measures efficiently. Here, we review currently known environmental risk factors that can influence the occurrence of ASF virus infection in wild boar when compared to disease occurrence in wild boar of a non-exposed reference scenario. Accordingly, the exposure of wild boar to environmental risk factors related to (1) climate, (2) land cover, (3) human activity, (4) wild boar and (5) ASF were evaluated. As key environmental risk factors in this review, increased ASF occurrence in wild boar was associated with seasonal patterns, forest coverage, presence of water, human presence, farming activities, wild boar density and ASF nearness. The review highlights inconsistencies in some of these risk factor associations with disease detection in space and time and may provide valuable insights for the investigation of ASF transmission dynamics. The examined risk information was applied to consider potential improvements of the ASF control strategy in wild boar regarding disease surveillance, hunting, wild boar carcass searches and ASF barrier implementation.

Reduced neurobehavioral functioning in agricultural workers and rural inhabitants exposed to pesticides in northern Chile and its association with blood biomarkers inhibition

BackgroundPrevious biomonitoring studies have shown that people in the rural population of Coquimbo, the major agricultural area in northern Chile are being occupationally and environmentally exposed to organophosphate/carbamate (OP/CB) pesticides. Given their harmful effects, this study had two aims; first, to evaluate the effect of cumulative or chronic exposure to OP/CB pesticides on the neurobehavioral performance of agricultural workers and rural inhabitants; second, to determine if changes in the neurobehavioral performance are associated to changes in blood biomarkers of OP/CB pesticides during the spray season, when exposure is higher.MethodsFor the first aim, a cross sectional study of neurobehavioral performance in adult volunteers (men and women, 18–50 years-old, right-handed) was carried out in the pre-spray season. Sampling was done by convenience and a questionnaire was used to categorize participants depending on their level of chronic exposure, as either: occupationally exposed (OE, n = 87), environmentally exposed (EE, n = 81), or non-exposed controls or reference group (RG, n = 100). A neurobehavioral test battery consisting of 21 tests to measure cognitive, motor and emotional state was applied. For the second aim, neurobehavioral measures were taken a second time from EE and OE groups during the spray season, and their exposure corroborated by blood-based biomarker inhibition.ResultsLower neurobehavioral performance was observed in the pre-spray evaluation of EE and OE groups compared to the non-exposed, OE being the worst performing group. Seasonal exposure impaired performance in both exposure groups on all tests except those on attention and mood. Data modeling of the basal (pre-spray) measurements showed that the level of exposure was the best predictor of performance. During spraying, inhibition of BChE activity in the EE group was the best predictor of low performance in tests measuring logical, auditory and visual memory, inhibitory control of cognitive interference, constructional and planning abilities, executive functions, and motor speed and coordination.ConclusionLong-term occupational or environmental exposure to pesticides caused impairment in neurobehavioral functioning, which worsened during the spraying season, mainly in EE. BChE inhibition was the best predictor for seasonal neurobehavioral changes in EE.

Impact of arsenic exposure on clinicopathological characteristics of bladder cancer: A comparative study between patients from an arsenic-exposed region and nonexposed reference sites

BackgroundBeyond exposure to arsenic in drinking-water, there is few information about demographic and clinicopathological features of patients with bladder cancer living in arsenic-exposed regions. The aim of the study was to assess the impact of arsenic exposure on clinicopathological characteristics in patients with bladder cancer from a contaminated region compared to those of 2 reference areas. MethodsData of 285 patients with bladder cancer (83 with arsenic exposure from Antofagasta and 202 controls from 2 different sites in Santiago) were obtained through personal interviews and from review of medical records. Demographic, clinicopathological parameters, and information on relevant environmental risk factors were compared with parametric and nonparametric tests as needed. Multivariable analysis was performed to identify independent predictors for high grade and muscle-invasive disease (T2-4). ResultsWe found no significant differences between groups regarding age at presentation (66.4 vs. 66.5 and 67.2 years; P = 0.69, for exposed vs. the 2 nonexposed groups, respectively) and female gender (28.9% vs. 29.8% and 26.2%; P = 0.84). Proportion of current smokers was significantly lower in the exposed population (10.7% vs. 38.6% and 26.9%; P < 0.001). There was a significantly higher proportion of locally advanced (10.8 vs. 1.8 and 0.7% T3/4; P = 0.002) and high-grade tumors (79.5% vs. 63.2% and 64.1%; P = 0.001) within arsenic-exposed patients. Arsenic exposure was the only significant predictor for the presence of high-grade tumors (adjusted OR: 5.10; 95%CI: 2.03–12.77) on multivariable analysis. ConclusionsOur study revealed relevant clinical differences in bladder cancer patients with a history of arsenic exposure as compared to nonexposed cases. The more aggressive phenotype associated to arsenic-related bladder cancer should be considered when designing efficient screening strategies for this high-risk population.

Argon-seeded plasma exposure and oxidation performance of tungsten-chromium-yttrium smart alloys

Tungsten-chromium-yttrium (WCrY) smart alloys are foreseen as the first wall material for future fusion devices such as Demonstration Power Plant (DEMO). While suppressing W oxidation during accidental conditions, they should behave like pure W during plasma operation due to preferential sputtering of the lighter alloying elements Cr, Y, and W enrichment of the surface. In this paper, the erosion performance of WCrY and W samples simultaneously exposed to deuterium (D) plasma with the addition of 1% of the projectile ions being argon (Ar) ions at an ion energy of 120 eV is compared. With reference to the previous experiments at 120 eV in pure D plasma, the erosion for both WCrY and W is enhanced by a factor of ~ 7. Adding Ar to the D plasma suppresses significant W enrichment previously found for pure D plasma. To investigate the impact of the plasma exposure onto the oxidation performance, plasma-exposed and non-exposed reference samples were oxidised in a dry atmosphere. Results show, on the one hand, that the oxidation suppression of WCrY in comparison to pure W is preserved during the plasma performance. On the other hand, it becomes evident that edge effects imposed by the geometry of the samples used in plasma experiments play a significant role for the oxidation behaviour.

Perinatal polychlorinated biphenyls and polychlorinated dibenzofurans exposure are associated with DNA methylation changes lasting to early adulthood: Findings from Yucheng second generation

Epigenome-wide DNA methylation has not been studied in men perinatally exposed to PCBs and dioxins. Therefore, we examined whether perinatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) induces sustained methylation changes lasting to early adulthood. We used the Illumina HumanMethylation450 BeadChip to assess DNA methylation in whole blood among Yucheng second generation (people perinatal exposed to high PCBs and PCDFs) compared with referents. Thirty male offspring from the Yucheng cohort were randomly selected and matched with 30 male offspring from the Yucheng’ neighborhood referents with similar backgrounds. Methylation differences between the Yucheng second generation and non-exposed referents were identified using a P value < 1.06 × 10−7. Differential DNA methylation with epigenome-wide statistical significance was observed for 20 CpGs mapped to 11 genes, and 19 CpGs were correlated with gestational levels of PCBs or PCDF toxic equivalency (PCDF-TEQ) with the same direction of effect. Among the 11 genes, AHRR and CYP1A1 are involved in the aryl hydrocarbon receptor signaling pathway known to mediate dioxin toxicity. MYO1G, FRMD4A, ARL4C, OLFM1, and WWC3 were previously reported to be related to carcinogenesis. This is the first study examining genome-wide DNA methylation among people perinatally exposed to high concentrations of PCBs and PCDFs. We observed novel differential methylation of several genes, indicating that modifications of DNA methylation associated with perinatal PCB and PCDF exposure may persist in exposed offspring for more than 20 years. Furthermore, involvement of several carcinogesis-related genes suggested a potential in utero epigenetic mechanisms.

DNA damage and epigenetic alteration in soybean farmers exposed to complex mixture of pesticides.

Exposure to pesticides can trigger genotoxic and mutagenic processes through different pathways. However, epidemiological studies are scarce, and further work is needed to find biomarkers sensitive to the health of exposed populations. Considering that there are few evaluations of soybean farmers, the aim of this study was to assess the effects of human exposure to complex mixtures of pesticides. The alkaline comet assay modified with restriction enzyme (hOGG1: human 8-oxoguanine DNA glycosylase) was used to detect oxidised guanine, and compared with the buccal micronucleus cytome assay, global methylation, haematological parameters, biochemical analyses (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma-glutamyl-transferase and butyrylcholinesterase), and particle-induced X-ray emission (PIXE) for the analysis of inorganic elements. Farm workers (n = 137) exposed to different types of pesticides were compared with a non-exposed reference group (control; n = 83). Results of the enzyme-modified comet assay suggest oxidation of guanine in DNA generated by pesticides exposure. It was observed that DNA damage (comet assay and micronucleus test) was significantly increased in exposed individuals compared to the unexposed group. The micronucleus test demonstrated elimination of nuclear material by budding, defective cytokinesis and dead cells. Occupationally exposed individuals also showed genomic hypermethylation of DNA, which correlated with micronucleus frequency. No differences were detected regarding the haematological and biochemical parameters. Finally, significantly higher concentrations of Al and P were observed in the urine of the soybean farmers. DNA damage could be a consequence of the ability of the complex mixture, including Al and P, to cause oxidative damage. These data indicate that persistent genetic instability associated with hypermethylation of DNA in soybean workers after long-term exposure to a low-level to pesticides mixtures may be critical for the development of adverse health effects such as cancer.

A possible link between famine exposure in early life and future risk of gastrointestinal cancers: Implications from age-period-cohort analysis.

The Chinese famine in 1958-1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983-2007, we calculated age-specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non-exposed reference cohort. Age-period-cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver and colorectal cancers was particularly high in men exposed to famine during early childhood (0-9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms.

Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure

Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from “El Cerrejón” (world’s largest open-cast coal mine located in Guajira – Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms. This modulation may involve specific and differentiated pathways in different tissues that also may cause a differential sensitivity related to differential induction of some enzymes.

Respiratory Symptoms and Infections in Children and Employees at a Water-Damaged Kindergarten

Objectives: Several studies have shown an increased risk of infections and respiratory symptoms among people exposed to molds. Here, we report the morbidity of children and staff exposed to several toxic molds at a kindergarten. Methods: Prevalence of symptoms and the incidence of infections were followed up and compared between children and staff exposed in a day-care center affected by mold and those in a reference day-care center. At both day-care centers, parents (mostly mothers) filled out a questionnaire. Staff members with more severe symptoms were examined at the Clinic for Indoor Air Health Problems of the Skin and Allergy Hospital, Helsinki University Hospital. Results: Children and staff exposed to mold had more frequent symptoms and illnesses such as hoarseness, bronchitis than the nonexposed reference group. Symptoms in the exposed group were reduced following remedial building work and the avoidance of exposure. In addition, the acute care visits of the children to the local health care center were less frequent after remediation. One of the employees of a water-damaged kindergarten was diagnosed with allergic alveolitis and asthma, one had epipharyngitis, and two had mixed cell inflammation of the eye. Conclusions: Our study supports the results in which moisture and mold problems have been noted to increase disease rates of children and staff in day-care facilities. The study also suggest that detrimental health effects can be diminished by decreasing or stopping the exposure.

Effects of Extreme Dilutions of Apis mellifica Preparations on Gene Expression Profiles of Human Cells.

Gene expression analysis has been employed in the past to test the effects of high dilutions on cell systems. However, most of the previous studies were restricted to the investigation of few dilutions, making it difficult to explore underlying mechanisms of action. Using whole-genome transcriptomic analysis, we investigated the effects of a wide range of Apis mellifica dilutions on gene expression profiles of human cells. RWPE-1 cells, a nonneoplastic adult human epithelial prostate cell line, were exposed to Apis mellifica preparations (3C, 5C, 7C, 9C, 12C, 15C, and 30C) or to the reference solvent solutions for 24 hours; nonexposed cells were also checked for gene expression variations. Our results showed that even the most diluted solutions retained the ability to trigger significant variations in gene expression. Gene pathway analysis revealed consistent variations in gene expression induced by Apis mellifica when compared to nonexposed reference cells but not to reference solvent solutions. Since the effects of Apis Mellifica at extreme dilutions did not show dose–effect relationships, the biological or functional interpretation of these results remains uncertain.

Influence of Focused Electron Beam on Electrical Characterization of Advanced Mosfets

The focused electron beam based inspection instruments such as Scanning Electron Microscope (SEM) have become widespread in the semiconductor manufacturing and failure analysis of scaled devices. Also, nano-probing systems with SEM guidance have become important in the failure analysis area to evaluate the localized device in the actual LSI [1]. However, electron beam leads to device degradation [2] and its damage are increasing with the scaling. As CMOS scaling is going to be sub-10nm regime [3], electron beam damages are becoming critical issue in performing electrical characterization at the contact level in integrated devices using nano-probe technique. To avoid the electron damage, the acceleration voltage should be lower. However, the lower acceleration voltage of electron beam leads to lower resolution of image created by SEM guidance.In this work, we evaluated NMOS FinFET in SRAM cells manufactured in a 10nm CMOS process with Atomic Force Microscopy (AFM) based nano-probing system. AFM based nano-probing system has no electron beam damage because it uses topography image created by AFM instead of SEM for guidance at contact level [4]. After deprocessing the samples to the contact level, we irradiated electron beams to samples to investigate a dependency of the device characteristics on electron beam acceleration voltage. Compared to a non-exposed reference transistor, the exposure of electron beam on the target transistor lead to significant changes on device characteristics such as saturation current (IDS), sub-threshold voltage (VTH) and sub-threshold swing (S). This might be due to trapped charges in the gate oxide and interface state [5]. Our studies show that it is critical to avoid electron beam exposure before electrical device characterizations are carried out at the contact level using nano-probe system since electron beam induced device parameter changes are not negligible in the failure analysis of sub-10nm devices.

Correlation of cadmium and aluminum in blood samples of kidney disorder patients with drinking water and tobacco smoking: related health risk.

The combined exposure to aluminum (Al) and cadmium (Cd) causes more pronounced adverse health effects on humans. The kidneys are the main organs affected by internal exposure to Cd and Al via food and non-food items. The objective of present study was to measure the Al and Cd concentrations in cigarettes tobacco (branded and non-branded) and drinking water (domestic treated, ground and lake water) samples in southern part of Pakistan, to assess the risk due to ingestion of water and inhalation of cigarettes smoke containing high concentrations of both elements. The study population (kidney disorder and healthy) divided into two group based on consuming lake and ground water, while smoking non-branded cigarette as exposed, while drinking domestic treated water and smoking branded cigarette as non-exposed. Electrothermal atomic absorption spectrometry was used to determined Cd and Al concentrations in tobacco, drinking water and blood samples. The resulted data indicated that the levels of Al and Cd in lake and underground water were higher than the permissible limit in drinking water recommended by the World Health Organization. The biochemical parameters of exposed and referent patients, especially urinary N-acetyl-h-glucosaminidase, were used as a biomarkers of kidney disorder. Exposed kidney disorder patients have higher levels of Cd and Al than the exposed referents subjects, while difference was significant when compared to resulted data of non-exposed patients and referents (p=0.01-0.001). The pearson correlation showed positive correlation between both toxic element concentrations in water, cigarettes versus blood samples of exposed subjects (r=0.20-0.67 and 0.71-0.82), while lower values were observed for non-exposed subjects (r=0.123-0.423 and 0.331-0.425), respectively.