Longer Duration Of Exposure Research Articles

Intraductal ultrasonography-directed endoscopic retrograde biliary drainage without fluoroscopy.

Common bile duct (CBD) stones may cause septic shock and lead to life-threatening conditions [1]. Endoscopic sphincterotomy (EST) and stone removal is an accepted method for the treatment of CBD stones [2]. EST has the potential to cause bleeding in patients with a bleeding risk. However, endoscopic retrograde biliary drainage (ERBD) can be performed effectively and safely without EST in these patients. ERBD has been performed under fluoroscopy, resulting in a relatively long duration of radiation exposure [3] [4]. Intraductal ultrasound (IDUS) provides real-time cross-sectional imaging within the bile duct. IDUS can be performed without fluoroscopy. Therefore, IDUS-directed ERBD can be used to reduce the time of radiation exposure for both examiners and patients. This report describes IDUS-directed ERBD with a plastic stent without fluoroscopy in patients with a risk of bleeding.

Environmental and occupational factors associated with chronic myeloid leukemia: a case-control study

BackgroundThe relationship between chronic myeloid leukemia (CML) and a broad range of exposures to occupational and environmental factors known to cause leukemia in general is limited. CML is by and large incurable and treatment is just palliative and life prolonging, with high case fatality rate, even in the best centers. Furthermore treatment is very expensive. Identification of leukemogenic factors is therefore important if this can lead to simple public health interventions.ObjectiveThe objective was to determine key environmental and occupational exposure factors that may be associated with CML.MethodsThis was a case-control study involving CML cases enrolled in Glivec International Patient Assistance Program (GIPAP) clinics at the Nairobi Hospital and Aga Khan University Hospital and two control groups for each case, matched for age and sex: a family- and hospital-based control, was carried out. One hundred and eight cases with ageand-gender-matched family- and hospital-based controls were recruited and a standard questionnaire was administered. Individual data on demographics, occupation, environment, and exposures to benzene and farm organochemical products were obtained. Clinical examination was carried out in control subjects. Statistical analysis was done using bivariate and multivariate analysis to look for associations between exposure factors and CML.ResultsThe median age at diagnosis of CML cases was 41.32 years with an age range of 8–81 years and a male to female ratio of 1.7:1. Most of our cases were concentrated in or around Nairobi. There was no significant correlation found for exposure to benzene or pesticides. Long duration of exposure to pesticides in the family control group was significantly associated (t-test, P = 0.017) with risk of CML.ConclusionsAssociations between exposures to organic solvents like pesticides and CML were indicated but were not entirely consistent, although no associations with benzene products were found. Nevertheless, for almost all cases of Ph chromosome-positive CML, other explanations must be sought for.

Is rumination after bereavement linked with loss avoidance? Evidence from eye-tracking.

Rumination is a risk factor in adjustment to bereavement. It is associated with and predicts psychopathology after loss. Yet, the function of rumination in bereavement remains unclear. In the past, researchers often assumed rumination to be a maladaptive confrontation process. However, based on cognitive avoidance theories of worry in generalised anxiety disorder (GAD) and rumination after post-traumatic stress disorder (PTSD), others have suggested that rumination may serve to avoid painful aspects of the loss, thereby contributing to complicated grief. To examine if rumination is linked with loss avoidance, an eye-tracking study was conducted with 54 bereaved individuals (27 high and 27 low ruminators). On 24 trials, participants looked for 10 seconds at a picture of the deceased and a picture of a stranger, randomly combined with negative, neutral or loss-related words. High ruminators were expected to show initial vigilance followed by subsequent disengagement for loss stimuli (i.e., picture deceased with a loss word) in the first 1500 ms. Additionally, we expected high ruminators to avoid these loss stimuli and to show attentional preference for non-loss-related negative stimuli (i.e., picture stranger with a negative word) on longer exposure durations (1500–10000 ms). Contrary to expectations, we found no evidence for an effect of rumination on vigilance and disengagement of loss stimuli in the first 1500 ms. However, in the 1500–10000 ms interval, high ruminators showed shorter gaze times for loss stimuli and longer gaze times for negative (and neutral) non-loss-related stimuli, even when controlling for depression and complicated grief symptom levels. Effects of rumination on average fixation times mirrored these findings. This suggests that rumination and loss avoidance are closely associated. A potential clinical implication is that rumination and grief complications after bereavement may be reduced through the use of exposure and acceptance-based therapeutic techniques.

Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness

ObjectiveWe aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (AMS).MethodsA total of 600 adult men were recruited. Subjects’ subjective sleep quality was evaluated by the Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system. Arterial oxygen saturation was measured.ResultsDespite insomnia resolution in only a few subjects, the prevalence of insomnia among insomniacs remained stable at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the prevalence of insomnia sharply increased to 32.13% in the first day of altitude exposure and progressively reduced to 4.26% by the 60th day of altitude stay. Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1 to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first, third, and seventh days, respectively, which was significantly higher than that among non-insomniacs. Multivariate regression revealed that elevated Athens Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio 1.388, 95% confidence interval: 1.314–1.464, P<0.001), whereas high arterial oxygen saturation and long duration of altitude exposure are protective factors against AMS.ConclusionOur results suggest that the effect of high-altitude exposure on subjective sleep quality is more marked, but disappears more quickly, among non-insomniacs than among insomniacs, whereas AMS is especially common among insomniacs. Moreover, poor subjective sleep quality is a risk factor for AMS.

Изменение компонентного состава древесины при гидротермической обработке

Wood is a product of plant origin having complex element and component composition. Under the influence of temperature in the presence of moisture lignocarbohydrate complex decomposes and extraction of water soluble substances takes place. Aqueous distillate contains a large number of different chemicals, the most dangerous of which are furfural and formaldehyde. The intensity of the process of extraction in the wood depends on the temperature. The formation of these substances is observed even at low temperatures around 60-70 º C and long duration of exposure, which is characteristic of conditions during chamber wood drying.

Trabectedin in soft tissue sarcomas.

Trabectedin (Yondelis®; PharmaMar, Madrid, Spain), a synthetic anticancer agent originally isolated from the Caribbean tunicate, Ecteinascidia turbinata, is currently approved in more than 70 countries worldwide for the treatment of soft tissue sarcoma (STS). Trabectedin is an isoquinoline alkylating agent that, unlike other alkylating agents, binds in the DNA minor groove to initiate cytotoxic activity. Other multitarget mechanisms of action of trabectedin include important effects within the tumor microenvironment; in particular, trabectedin possesses indirect anti-inflammatory and anti-angiogenic activity via tumor-associated macrophages and high-specificity modulation of various transcription factors. The clinical efficacy of trabectedin, administered intravenously over 24 h every 3 weeks, has been demonstrated in several studies in patients with STS. In the Phase II STS-201 trial, 270 patients with liposarcoma or leiomyosarcoma were randomized to receive trabectedin 1.5 mg/m(2) given as a 24-h intravenous (iv.) infusion every 3 weeks or as a weekly regimen (0.58 mg/m(2); 3-h iv. infusion for three consecutive weeks in a 4-week cycle). There was a statistically significant and clinically relevant 27% reduction in the risk of disease progression (primary end point) with trabectedin given as a 24-h infusion q3w (p = 0.0302) with an overall survival rate at 12 months of 60%. Trabectedin was generally well tolerated; the most frequently reported severe adverse events were neutropenia (47% of patients) and elevated transaminases (47%). Overall, the majority of adverse events were mild to moderate and, despite a long duration of exposure to trabectedin in some patients, no cumulative toxicities were experienced.

Parental smoking exposure and adolescent smoking trajectories.

In a multigenerational study of smoking risk, the objective was to investigate the intergenerational transmission of smoking by examining if exposure to parental smoking and nicotine dependence predicts prospective smoking trajectories among adolescent offspring. Adolescents (n = 406) ages 12 to 17 and a parent completed baseline interviews (2001-2004), and adolescents completed up to 2 follow-up interviews 1 and 5 years later. Baseline interviews gathered detailed information on parental smoking history, including timing and duration, current smoking, and nicotine dependence. Adolescent smoking and nicotine dependence were assessed at each time point. Latent Class Growth Analysis identified prospective smoking trajectory classes from adolescence into young adulthood. Logistic regression was used to examine relationships between parental smoking and adolescent smoking trajectories. Four adolescent smoking trajectory classes were identified: early regular smokers (6%), early experimenters (23%), late experimenters (41%), and nonsmokers (30%). Adolescents with parents who were nicotine-dependent smokers at baseline were more likely to be early regular smokers (odds ratio 1.18, 95% confidence interval 1.05-1.33) and early experimenters (odds ratio 1.04, 95% confidence interval 1.04-1.25) with each additional year of previous exposure to parental smoking. Parents' current non-nicotine-dependent and former smoking were not associated with adolescent smoking trajectories. Exposure to parental nicotine dependence is a critical factor influencing intergenerational transmission of smoking. Adolescents with nicotine-dependent parents are susceptible to more intense smoking patterns and this risk increases with longer duration of exposure. Research is needed to optimize interventions to help nicotine-dependent parents quit smoking early in their children's lifetime to reduce these risks.

Mobile phone radiation alters proliferation of hepatocarcinoma cells.

This study investigated the effects of intermittent exposure (15 min on, 15 min off for 1, 2, 3, or 4 h, at a specific absorption rate of 2 W/kg) to enhanced data rates for global system for mobile communication evolution-modulated radiofrequency radiation (RFR) at 900- and 1,800-MHz frequencies on the viability of the Hepatocarcinoma cells (Hep G2). Hep G2 cell proliferation was measured by a colorimetric assay based on the cleavage of the tetrazolium salt WST-1 by mitochondrial dehydrogenases in viable cells. Cell injury was evaluated by analyzing the levels of lactate dehydrogenase (LDH) and glucose released from lysed cells into the culture medium. Morphological observation of the nuclei was carried out by 4',6-diamidino-2-phenylindole (DAPI) staining using fluorescence microscopy. In addition, TUNEL assay was performed to confirm apoptotic cell death. It was observed that cell viability, correlated with the LDH and glucose levels, changed according to the frequency and duration of RFR exposure. Four-hour exposure produced more pronounced effects than the other exposure durations. 1,800-MHz RFR had a larger impact on cell viability and Hep G2 injury than the RFR at 900 MHz. Morphological observations also supported the biochemical results indicating that most of the cells showed irregular nuclei pattern determined by using the DAPI staining, as well as TUNEL assay which shows DNA damage especially in the cells after 4 h of exposure to 1,800-MHz RFR. Our results indicate that the applications of 900- and 1,800-MHz (2 W/kg) RFR cause to decrease in the proliferation of the Hep G2 cells after 4 h of exposure. Further studies will be conducted on other frequency bands of RFR and longer duration of exposure.

Metal accumulation and antioxidant defenses in the freshwater fish Carassius auratus in response to single and combined exposure to cadmium and hydroxylated multi-walled carbon nanotubes

The effects of cadmium, hydroxylated multi-walled carbon nanotubes, and their mixture on metal accumulation and antioxidant defenses were studied using the goldfish Carassius auratus as the test organism. The fish were exposed to 0.1mg/L Cd, 0.5mg/L OH-MWCNTs, or 0.1mg/L Cd+0.5mg/L OH-MWCNTs for 3 and 12 days. Then, the Cd concentration was determined in the gill, liver and muscle. Moreover, hepatic antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase), glutathione level and malondialdehyde content were also measured. A continuous accumulation of Cd was observed throughout the experimental period. Cd accumulation in tissues occurred in the following order: gill>liver>muscle at 3 days and liver>gill>muscle at 12 days. The concentrations of Cd in the livers of fish exposed to the combination of Cd+OH-MWCNTs were significantly higher than those in fish exposed to either single chemical after 12 d of exposure. Meanwhile, the mixture evoked severe oxidative stress in the exposed fish, as indicated by significant inhibition of SOD, CAT and GPx activity, a remarkable decrease in GSH level, and simultaneous elevation of MDA content. These results suggested that the effect of the combined factors on metal accumulation and oxidative stress biomarkers was more obvious than that of single factors at longer exposure durations.

High performance dual-wave mode flexible surface acoustic wave resonators for UV light sensing

Dual-mode flexible ZnO/polyimide surface acoustic wave (SAW)-based ultraviolet (UV) light sensors were fabricated and their performance was investigated. UV light sensing measurements showed that the responses of the dual wave modes of the sensors increase with the increase of light intensity and the frequency changes linearly with the change of light intensity. Under a 4.5 mW cm−2 UV light illumination, the resonant frequency of the Rayleigh wave decreased up to ∼43 kHz, while that of the Lamb wave was approximately 76 kHz. The UV light sensitivities for the two resonant modes are 111.3 and 55.8 ppm (mW cm−2)–1, respectively. The resonant frequency, phase angle and amplitude of the two resonant modes exhibited a good repeatability in responding to cyclic change of the UV light, and an excellent stability up to a long duration of UV light exposure. The dual-mode flexible SAW resonators are simple in structure, more accurate in detection, and can be fabricated at low cost are, therefore, very promising for application in flexible sensors and electronics.

Toxic effects of gentamicin in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9

Gentamicin is an aminoglycoside antibiotic and is used to treat various Gram negative bacteria. Due to its thermal stability it is useful for the preparation of culture media for various cell lines and microorganisms. It has been reported as ototoxic and nephrotoxic in adult humans. In the present study the toxic effects of gentamicin were studied in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9. The third instar larvae were exposed to a wide range of doses, i.e. 60, 70, 80, 90 and 100 μg ml−1 of gentamicin for 6, 12, 24 and 48 hours. The exposure of larvae to the above doses for 6 and 12 hours did not show any toxic effects. The exposure of larvae to 80, 90 and 100 μg ml−1 of gentamicin for 24 hours and 70, 80, 90 and 100 μg ml−1 of gentamicin for 48 hours showed a dose-dependent toxic effect. The dose of 60 μg ml−1 did not show any toxic effects and hence can be suggested as the No Observed Adverse Effect Level (NOAEL). The results suggest that gentamicin is toxic at higher doses and longer duration of exposure.

A Review on the Relationship between SGLT2 Inhibitors and Cancer

Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted.

Dwelling on Courtyards. Exploring the energy efficiency and comfort potential of courtyards for dwellings in the Netherlands

Dwelling on Courtyards. Exploring the energy efficiency and comfort potential of courtyards for dwellings in the Netherlands

Dwelling on Courtyards

Dwelling on Courtyards

Dwelling on Courtyards. Exploring the energy efficiency and comfort potential of courtyards for dwellings in the Netherlands

Dwelling on Courtyards. Exploring the energy efficiency and comfort potential of courtyards for dwellings in the Netherlands

Dwelling on Courtyards. Exploring the energy efficiency and comfort potential of courtyards for dwellings in the Netherlands

Dwelling on Courtyards. Exploring the energy efficiency and comfort potential of courtyards for dwellings in the Netherlands

Treatment with Gefitinib or Lapatinib Induces Drug Resistance through Downregulation of Topoisomerase IIα Expression

The EGF receptor (EGFR) is therapeutically targeted by antibodies and small molecules in solid tumors including lung, colorectal, and breast cancer. However, chemotherapy remains important, and efforts to improve efficacy through combination with targeted agents is challenging. This study examined the effects of short and long durations of exposure to the EGFR- and HER2-targeted tyrosine kinase inhibitors (TKI) gefitinib and lapatinib, on induction of cell death and DNA damage by topoisomerase IIα (Topo IIα) poisons, in the SK-Br-3 HER2-amplified breast cancer cell line. Short exposure to either gefitinib or lapatinib for 1 hour did not affect the induction of apoptosis by the Topo IIα poisons doxorubicin, etoposide, and m-AMSA. In contrast, cells treated for 48 hours were resistant to all three drugs. Short exposure (1 hour) to TKI did not alter the number of DNA single- or double-strand breaks (DSB) induced, whereas longer exposure (48 hours) reduced the number of DNA DSBs and the formation of γ-H2AX foci. Both gefitinib and lapatinib reduced the expression and activity of Topo IIα at 48 hours. Studies using a cell line with inducible downregulation of Topo IIα showed that expression of Topo IIα, and not Topo IIβ, determined the number of DNA strand breaks induced by these chemotherapeutic agents. These results indicate that prolonged exposure to TKIs targeting EGFR and HER2 induce resistance to doxorubicin, etoposide, and m-AMSA through downregulation of Topo IIα. This may explain why their addition to chemotherapy regimens have not increased efficacy.

Mobile phone radiation alters proliferation of hepatocarcinoma cells

This study investigated the effects of intermittent exposure (15 min on, 15 min off for 1, 2, 3 or 4 hrs) to Enhanced Data rates for Global System for Mobile Communication Evolution (GSM EDGE) modulated radiofrequency radiation (RFR) at 900 MHz and 1800 MHz frequencies on the viability of the hepatocarcinoma cells (Hep G2). Hep G2 cell proliferation was measured by a colorimetric assay based on the cleavage of the tetrazolium salt [2-(4-Iodophenyl)-3-(4-nitrophenyl)-5 (2,4-disulfophenyl)-2H-tetrazolium] (WST-1) by mitochondrial dehydrogenases in viable cells. Cell injury was evaluated by analyzing the levels of lactate dehydrogenase (LDH) and glucose released from lysed cells into the culture medium. Morphological observation of the nuclei was carried out by 4,6-diamidino-2-phenylindole (DAPI) staining using fluorescence microscopy. In addition, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assay was performed to confirm apoptotic cell death. It was observed that cell viability, correlated with the LDH and glucose levels, changed according to the frequency and duration of RFR exposure. Four-hour-exposure produced more pronounced effects than the other exposure durations. 1800-MHz RFR had more impact on cell viability and injury of Hep G2 than the RFR at 900 MHz. Morphological observations also supported the biochemical results that most of the cells showed irregular nuclei pattern as a marker of late stage apoptosis using the DAPI staining, as well as TUNEL assay which shows DNA damage especially in the cells after 4 hrs of exposure to 1800- MHz RFR. The results showed that proliferation of Hep G2 cells increased after 1 hour of exposure whereas a decrease was observed after four hours of-exposure to the 1800-MHz radiation. The 900-MHz radiation had no significant effect on cell proliferation after 1 hour of exposure, but a decrease was observed after 4 hrs of exposure. Further studies will involve other frequency bands of RFR and longer duration of exposure.

The radiating K&amp;K mining authority in Vienna: environmental radiological evaluation one century after the end of the Austrian monarchy

Background: Radon has been shown to increase the risk of lung cancer. In this study, employees working in the former K&amp;K mining authority building in Vienna, Austria, requested an assessment of their health risk from their exposure to radon from the historical storage and sale of radium in the building (until 1914). Methods: Measurements (68 ambient dose rate and three radon measurements) were performed both inside (8 rooms) and outside of the building by a certified institute. Nuclides were identified by gamma spectroscopy. Radon concentrations in air were measured by Alphaspectroscopy (AlphaGuard©). Furthermore, the duration of exposure for employees at various work places in the past four years was assessed. Results: The maximum ambient dose rates at the work places (office desks) were between 0.2 and 2.0 µSv/h. Higher values were measured in niches and on the floor (up to 300 µS/h). Ambient outdoor dose rates were below 0.08 µS/h. Ra226 was identified as major nuclide. Rn-levels were above 240 Bq/m³. The longest duration of exposure at the work places was approx. 480 hours (over four years). After adjustment for the different locations a total exposure of approx. 240 µS was calculated for that employee. Discussion: Compared to the local ambient background levels around the building, a significantly higher exposure was detected in the offices. The total dose in two office rooms was also above the threshold values for the general population (1 mSv/a). The excess unit lifetime risk for the employee based on an additional exposure to 240 µSv is by application of a linear no-threshold model 1.32x10-6. Applying a preventive approach the use of the office rooms as permanent working places should be restricted.

Frequency of drug-induced valvular heart disease in patients previously exposd to benfluorex: a multicentre prospective study

The epidemiologic link between benfluorex use and an increased global frequency of left heart valve regurgitation has been well documented. However, no data linking previous drug exposure to the frequency of diagnosis of drug-induced valvular heart disease (DI-VHD) are available. The present study was conducted to address this issue. This echocardiography reader-blinded, controlled study conducted in 10 centres between February 2010 and February 2012 prospectively included 835 subjects previously exposed to benfluorex referred by primary care physicians for echocardiography. Based on blinded off-line analysis, echocardiography findings were classified as: (i) DI-VHD⁺ for patients with an echocardiographic diagnosis of DI-VHD, (ii) inconclusive, and (iii) DI-VHD⁻ for patients without signs of DI-VHD. Fifty-seven (6.8%) patients exposed to benfluorex were classified as DI-VHD⁺, 733 (87.8%) patients were classified as DI-VHD⁻, and 45 (5.4%) were classified as inconclusive. Mitral and aortic DI-VHD were reported in 43 patients (5.1%) and 30 (3.6%) patients, respectively. Longer duration of exposure, female gender, smoking, and lower BMI were independently associated with a diagnosis of DI-VHD. Good inter-observer reproducibility was observed for the echocardiography classification (Kappa = 0.83, P < 0.00001). About 7% of patients without a history of heart valve disease previously exposed to benfluorex present echocardiography features of DI-VHD. Further studies are needed to study the natural history of DI-VHD and to identify risk factors for the development of drug-induced valve lesions.