Total Duration Of Exposure Research Articles

P522 Prior pharmacotherapy patterns among patients with IBD in the USA initiating biologic therapy

Abstract Background Treatment for inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]) has shifted from symptom management using corticosteroids to targeted therapies such as tumour necrosis factor (TNF) inhibitors. An increase in therapeutic options warrants a better understanding of current treatment pathways. This study reports on the pharmacotherapy history of patients with CD and UC prior to initiation of an IBD-targeted biologic. Methods Using the US IQVIA™ Real-World Data Adjudicated Claims Database, we identified adults (≥18 years) with CD or UC who initiated biologics indicated for these diseases from 1 January 2016 to 30 June 2017. Patients were stratified based on the most recent biologic received; the date of initiation was designated the index date. Patients with < 12 months of continuous medical coverage prior to the index date were excluded. Patterns of prior IBD-related pharmacotherapy, in terms of the number and type of biologics, and time spent receiving the biologic, were examined in relation to the index biologic for the study period 1 January 2011 to 30 June 2017. Results In total, 3010 patients with UC and 5210 with CD were identified. Among patients with UC, 1285, 977, 587 and 161 initiated treatment with adalimumab, infliximab, vedolizumab and golimumab, respectively. Among patients with CD, 2634, 1436, 737, 241 and 162 began treatment with adalimumab, infliximab, vedolizumab, certolizumab and ustekinumab, respectively. Most patients beginning treatment with infliximab or adalimumab were biologic-naïve (UC: 79.9%, 89.3%, respectively; CD: 77.8%, 84.6%, respectively). Patients starting treatment with other biologics, however, had typically received at least one IBD-related biologic previously (Figure 1). Among patients who were not biologic-naïve at initiation of therapy, the mean total duration of prior biologic exposure was 17.8 months and 26.6 months for patients with UC and CD, respectively. Conclusion During the study period, anti-TNFs were the most commonly initiated biologics in both groups of patients. Although newer IBD-related biologics (i.e. vedolizumab and ustekinumab) are typically preceded by treatment with other biologics, most patients receiving an anti-TNF are biologic-naïve.

Health risk assessment of nitrate using a probabilistic approach in groundwater resources of western part of Iran

A probabilistic risk assessment (PRA) using two-dimensional Monte Carlo analysis was followed to inspect the health risk associated with consumption of groundwater contaminated with nitrate in 26 wells located in rural areas of Malayer, Iran. In this technique, probability distributions were assigned to the concentration of nitrate in groundwater, daily intake rate of water, frequency of exposure together with total duration of exposure and the risk levels were worked out for adults and children, accordingly. In addition, four scenarios were investigated with an emphasis on the effect of correlation between exposure frequency and ingestion rate of water on estimated risk values. It was indicated that inclusion of correlation between parameters would influence the upper median quartile values of estimated risk however the total impact on the results of health risk assessment is not significant. Moreover, considering the 3rd quartile value of risk level for the total size of the study area, the risk level related to children was higher than that of the adults with respective values of 0.621 and 0.989. The spatial variation of nitrate was considered using ordinary kriging and a novel combined method of random forest and spatial proximity as covariate. It was concluded that the predictions made by ordinary kriging were more accurate than the random forest technique which can be attributed to the small data sets used in this research.

Continuous Quality Improvement of Radiation Safety Management for Treatment of Differentiated Thyroid Carcinoma with Iodine-131

Purpose: To explore the effect of continuous quality improvement (CQI) of radiation safety management for patients administerediodine-131 after thyroid cancer surgery. Methods: A total of 103 patients with differentiated thyroid carcinoma were randomly divided into control and experimental groups containing 51 and 52 patients, respectively. In the control group, the drug was administered according to the operating procedure for iodine-131 treatment of thyroid carcinoma. In the experimental group, CQI was adopted to manage the radiation safety of care in addition to the conventional iodine-131 thyroid cancer treatment procedures. We also improved radiation safety protection measures prior to drug administration, developed a flow chart of drug administration for patients, established a patient preview of the drug administration process, and enhanced health education and psychological intervention for the patient. Results: The environmental radiation around the drug delivery window was reduced (P< 0.05), total duration of exposure to the radiation was shortened (P< 0.05), drug drop rate was decreased to 0%, and patient satisfaction was improved in the experimental group compared to the control group. Conclusions: Application of CQI for management of radiation safety when treating thyroid cancer withiodine-131 can improve patient treatment, quality of care, and satisfaction and reduce radiation pollution in the surrounding environment and radiation injury to staff.

Ordered subsets Non-Local means constrained reconstruction for sparse view cone beam CT system.

Sparse-view sampling scans reduce the patient's radiation dose by reducing the total exposure duration. CT reconstructions under such scan mode are often accompanied by severe artifacts due to the high ill-posedness of the problem. In this paper, we use a Non-Local means kernel as a regularization constraint to reconstruct image volumes from sparse-angle sampled cone-beam CT scans. To overcome the huge computational cost of the 3D reconstruction, we propose a sequential update scheme relying on ordered subsets in the image domain. It is shown through experiments on simulated and real data and comparisons with other methods that the proposed approach is robust enough to deal with the number of views reduced up to 1/10. When coupled with a CUDA parallel computing technique, the computation speed of the iterative reconstruction is greatly improved.

Interactive website for head and neck cancer patients: Adherence and coping program to prevent dysphagia after radiation

IntroductionPharyngeal and laryngeal cancers are highly curable; however survivors are at high risk for long-term dysphagia after radiation. To address lack of access to preventive care in community settings, we developed a responsive web-based application to help patients adhere to preventive swallowing exercises and cope with radiation side effects. We conducted an interim study analysis to determine website usage characteristics and to examine the effect size for future trials. MethodsPharyngeal and laryngeal cancer patients were recruited for enrollment by speech language pathologists before primary radiation and introduced to the interactive website. The program (English and Spanish) features tracking logs for preventive exercises, instructional videos, patient stories and search features. Patients' self-reported swallowing function was assessed with the MD Anderson Dysphagia Inventory (MDADI) at baseline and at 6 months. Adherence to preventive exercises was assessed during the 10 week intervention. Number of unique website visits, total duration of website exposure, and rankings of the most popular webpages were calculated. Preliminary regression models were run using adherence and MDADI as outcomes. ResultsOf the 160 enrolled, 96 had 10-week adherence data and 61 had 6-month MDADI data. The average age was 63 (SD = 12.26), 49.4% were from rural counties, 44% had a high school education or lower, and 42% reported annual income of $30,000 or less. The average number of visits was 5.49 (SD = 9.96) and the average total time spent with the website was 41.09 min (SD =88.48). Preliminary analyses indicated that number of unique visits to the website was independently associated with increased adherence to preventive exercises (p = .001–.008). ConclusionOur website showed significant effects in promoting adherence to swallowing exercises. However, our return visit rate showed that the platform needs improvement in navigability and usability for this older population undergoing challenging treatment in community settings with low resources.

2892. The Relationship Between Inpatient and Post-discharge Antimicrobial Use at the Hospital-level Across an Integrated Healthcare Network

BackgroundHospital-based antimicrobial stewardship interventions and metrics have typically focused only on inpatient antimicrobial exposure. However, single-center studies have found a large portion of antimicrobial exposure occurs immediately after hospital discharge. We sought to describe antimicrobial-prescribing upon hospital discharge across the Veterans Health Administration (VHA) and to compare inpatient and post-discharge antimicrobial use at the hospital-level.MethodsThis retrospective study used national VHA administrative data to identify all acute-care admissions from January 1, 2014 to December 31, 2016. Post-discharge antimicrobials were defined as oral outpatient antimicrobials prescribed at the time of hospital discharge. We measured inpatient-days of therapy (DOT) and post-discharge DOTs. At the hospital-level, inpatient DOTs per 100 admissions were compared with post-discharge DOTs per 100 admissions using Spearman’s rank-order correlation.ResultsAmong 1.7 million acute-care admissions across 122 VHA hospitals, 46.1% were administered inpatient antimicrobials and 19.9% were prescribed an oral antimicrobial at discharge. Fluoroquinolones were the most common antimicrobial prescribed at discharge among 335,396 antimicrobial prescriptions (38.3%). At the hospital-level, median inpatient antimicrobial use was 331.3 DOTs per 100 admissions (interquartile range (IQR) 284.9–367.9) and median post-discharge use was 209.5 DOTs per 100 admissions (IQR 181.5–239.6). Thirty-nine percent of the total duration of antimicrobial exposure occurred after hospital discharge. The metrics of inpatient DOTs per 100 admissions and post-discharge DOTs per 100 admissions were weakly correlated at the hospital-level (rho = 0.44, P < 0.0001).ConclusionAntimicrobial-prescribing at hospital discharge was common and contributed substantially to the total antimicrobial exposure associated with an acute-care hospital stay. A hospital’s inpatient antimicrobial use was only weakly correlated with its post-discharge antimicrobial use. Antimicrobial stewardship interventions should specifically target antimicrobial-prescribing at discharge.Disclosures All Authors: No reported Disclosures.

Post-discharge oral antimicrobial use among hospitalized patients across an integrated national healthcare network

ObjectivesAntimicrobial stewardship programmes have focused on reducing inappropriate inpatient antimicrobial prescribing, but several small studies have found a large portion of antimicrobial exposure occurs immediately after hospital discharge. In this study, we describe the prescribing of oral antimicrobials at hospital discharge across an integrated national healthcare system. At the hospital level, we also compare total inpatient antimicrobial use and post-discharge oral antimicrobial use. MethodsThis retrospective cross-sectional study used national administrative data to identify all acute-care admissions during 2014–2016 within the Veterans Health Administration (VHA). We evaluated inpatient days of therapy (DOT) and post-discharge DOT, defined as oral outpatient antimicrobials dispensed at the time of hospital discharge. At the hospital level, inpatient DOT/100 admissions were compared with post-discharge DOT/100 admissions using Spearman's rank-order correlation. ResultsThere were 1 681 701 acute-care admissions across 122 hospitals, and 335 369 (19.9%) were prescribed an oral antimicrobial at discharge. Fluoroquinolones (38.3%) were the most common post-discharge antimicrobial. At the hospital level, median inpatient antimicrobial use was 331.3 (interquartile range (IQR) 284.9–367.9) DOT/100 admissions and median post-discharge use was 209.5 (IQR 181.5–239.6) DOT/100 admissions. Thirty-nine per cent of the total duration of antimicrobial exposure occurred after discharge. At the hospital-level, the metrics of inpatient DOT/100 admissions and post-discharge DOT/100 admissions were weakly positively correlated with rho=0.44 (p < 0.001). ConclusionsA large proportion of antimicrobial exposure among hospitalized patients occurred immediately following discharge. Antimicrobial-prescribing at hospital discharge provides an opportunity for antimicrobial stewardship. Hospital-level stewardship metrics need to include both inpatient and post-discharge antimicrobial-prescribing to provide a comprehensive assessment of hospital-associated antimicrobial use.

Radiation Dose to the Eye Lens Through Radiological Imaging Procedures at the Surgical Workplace During Trauma Surgery.

Background: Due to the drastic reduction of the eye lens dose limit from 150 mSv per year to 20 mSv per year since 2018, the prospective investigation of the estimated dose of the eye lens by radiological imaging procedures at the surgical site during trauma surgery in the daily work process was carried out. This was also necessary because, as experience shows, with changes in surgical techniques, there are also changes in the use of radiological procedures, and thus an up-to-date inventory can provide valuable information for the assessment of occupationally induced radiation exposure of surgical personnel under the current conditions. Methods: The eye lens radiation exposure was measured over three months for five trauma surgeons, four hand surgeons and four surgical assistants with personalized LPS-TLD-TD 07 partial body dosimeters Hp (0.07). A reference dosimeter was deposited at the surgery changing room. The dosimeters were sent to the LPS (Landesanstalt für Personendosimetrie und Strahlenschutzausbildung) measuring institute (National Institute for Personal Dosimetry and Radiation Protection Training, Berlin) for evaluation after 3 months. The duration of the operation, occupation (assistant, surgeon, etc.), type of surgery (procedure, diagnosis), designation of the X-ray unit, total duration of radiation exposure per operation and dose area product per operation were recorded. Results: Both the evaluation of the dosimeters by the trauma surgeons and the evaluation of the dosimeters by the hand surgeons and the surgical assistants revealed no significant radiation exposure of the eye lens in comparison to the respective measured reference dosimeters. Conclusions: Despite the drastic reduction of the eye lens dose limit from 150 mSv per year to 20 mSv per year, the limit for orthopedic, trauma and hand surgery operations is well below the limit in this setting.

420 Assessing the Prevalence of Gastroesophageal Reflux in Gastroparesis: Putting the G Back in GERD

INTRODUCTION: Patients with gastroparesis experience a wide range of symptoms from early satiety to frequent emesis and severe abdominal pain. However, few studies have evaluated concomitant underlying esophageal pathology or frequency of gastroesophageal reflux episodes in patients diagnosed with gastroparesis. Prolonged gastric emptying may lead to increased intra-gastric pressure and volume of gastric contents that may result in increased frequency of distal esophageal reflux events. The aim of this study was to assess for significant differences in total duration of distal esophagus acid exposure and number of gastroesophageal reflux events as detected by impedance pH testing between gastroparesis and control cohorts. METHODS: A retrospective analysis of 84 patient charts who underwent both 4-hour gastric emptying studies and 24-hour ambulatory pH testing was performed. Patients with gastroparesis, as documented by abnormal 4-hour gastric emptying studies, were compared with age and gender matched controls. Patients taking PPI during testing were excluded from the study. Percent of total distal esophageal time pH &lt; 4 (nl &lt; 4%) and impedance values (nl&lt; 53) were compared between the gastroparesis and control groups. Continuous variables were analyzed using independent 2-tailed t-test, while categorical values were evaluated using a chi squared analysis. RESULTS: Forty-two gastroparesis patients (9 men and 33 women, median age 46 years old, range 19-81 years old) underwent 24-hour ambulatory pH monitoring while off of PPI. When comparing total mean impedance events during pH testing, the gastroparesis cohort experienced significantly more episodes of distal esophageal reflux events, 61.27 ± 11.34 vs 45.81 ± 7.72 (P = 0.028), respectively. Mean percent total distal time for esophageal pH &lt; 4.0 was higher for the gastroparesis group when compared to controls, 4.79 ± 1.48% vs 3.31 ± 1.15% (P = 0.125), respectively. CONCLUSION: This pilot study demonstrates that patients meeting criteria for gastroparesis by gastric emptying study have significantly higher number of reflux episodes than those with normal gastric emptying. Trends toward a higher percentage of total distal esophageal acidity exposure time and a higher proportion of the gastroparesis group meeting diagnostic criteria for GERD were also seen. In the future, expanding sample sizes to better investigate these preliminary trends will be beneficial to better understand the association of GERD and gastroparesis.

2920 Prior Pharmacotherapy Patterns Among Patients With IBD in the USA Initiating Biologic Therapy

INTRODUCTION: Treatment for inflammatory bowel disease (IBD: Crohn's disease [CD] and ulcerative colitis [UC]) has shifted from symptom management using corticosteroids to targeted therapies such as tumor necrosis factor (TNF) inhibitors. Increasing therapeutic options warrants a better understanding of current treatment pathways. This study reports on the pharmacotherapy history of patients with CD and UC prior to initiation of an IBD-targeted biologic. METHODS: Using the IQVIATM Real-World Data Adjudicated Claims Database – US, we identified adults (≥18 years) with CD or UC who initiated biologic treatment from Jan 1, 2016 to Jun 30, 2017. Analysis was limited to biologics indicated for CD/UC during the study period. Patients were stratified based on most recent biologic received; the date of initiation was designated the index date. Patients with &lt;12 months of continuous medical coverage prior to the index date were excluded. Patterns of prior IBD-related pharmacotherapy, in terms of number and type of biologics, and time spent on the biologic, were examined in relation to the index biologic, for the study period Jan 1, 2011 to Jun 30, 2017. RESULTS: A total of 5210 patients with CD and 3010 with UC were identified. Among patients with CD, 2634, 1436, 737, 241 and 162 began treatment with adalimumab, infliximab, vedolizumab, certolizumab, and ustekinumab, respectively. Among patients with UC, 1285, 977, 587 and 161 initiated treatment with adalimumab, infliximab, vedolizumab and golimumab, respectively. Most patients beginning treatment with infliximab or adalimumab were previously biologic-naïve (CD: 77.8%, 84.6%, respectively; UC: 79.9%, 89.3%, respectively). Patients starting treatment with other biologics, however, typically had received at least one IBD-related biologic previously (Figure 1). Among patients who were not biologic-naïve at initiation of therapy, mean total duration of prior exposure was 26.6 and 17.8 months for patients with CD and UC, respectively. CONCLUSION: While newer IBD-related biologics (i.e., vedolizumab, ustekinumab) are typically preceded by treatment with other biologics, most patients receiving one of the first biologics approved for IBD (i.e., infliximab, adalimumab) are biologic-naïve. Patients with a treatment history of two biologics had a longer overall period of biologic exposure than those who had previously received only one biologic.

Iatrogenic Opiate Withdrawal in Pediatric Patients: Implementation of a Standardized Methadone Weaning Protocol and Withdrawal Assessment Tool

Methadone is frequently used to prevent withdrawal symptoms secondary to intended therapeutic opiate exposure. Absence of a standardized dose weaning strategy potentially results in increased exposure to narcotics and/or withdrawal symptoms. We sought to quantify the effect of implementing a standardized methadone weaning protocol and withdrawal assessment tool on methadone exposure and opiate withdrawal in pediatric patients receiving 5 or more days of continuous morphine or fentanyl infusions. The preintervention phase included patients weaned off of opiate infusions before implementation of a standardized weaning protocol and withdrawal symptom scoring tool. Patients in the postintervention phase were started on a standardized methadone wean based on total duration and dose of continuous opiate infusion exposure in the 24 hours preceding methadone initiation. Patients received either a 5- or 10-day wean, with the total daily methadone dose reduced by 20% daily or every other day, respectively. Patients in the postintervention phase were monitored for withdrawal using the withdrawal assessment tool (WAT-1). Postintervention patients were compared to preintervention patients treated with methadone. Total methadone duration decreased significantly from a median of 17 (13-22 interquartile range [IQR]) to 5 (5-10 IQR) days (P = .00001) after implementation of the methadone weaning protocol. Number of morphine boluses administered increased from a median of 3 (0-6 IQR) to 4 (0-5 IQR) doses per patient (P = .45). Demographic data were similar between both groups. Patients in the postintervention phase had significant reductions in methadone exposure after implementation of a standardized methadone weaning protocol and assessment tool.

MiRNAs deregulation in serum of mice is associated with lung cancer related pathway deregulation induced by PM2.5

Ambient fine particulate matter (PM2.5) as an environmental pollution has been associated with the lung cancer. However, the mechanism of epigenetics such as miRNAs deregulation between PM2.5-exposure and lung cancer has not been elucidated clearly. Twenty C57BL/6 mice were divided randomly into 2 groups and exposed to the filtered air (FA) and the concentrated air (CA), respectively. The FA mice were exposed to filtered air in chambers with a high-efficient particulate air filter (HEPA-filter), and the CA mice were exposed to concentration ambient PM2.5. The total duration of exposure was performed 6 h per day from December 1st, 2017 to January 27th, 2018. The mice exposed 900.21 μg/m3 PM2.5 for 6 h per day in CA chamber, which was nearly equaled to 225.05 μg/m3 for 24-h calculatingly. After exposure, the serum miRNAs levels were detected by microarray. Genetic and pathological alterations in lung of mice with/without PM2.5 exposure were detected. 38 differential miRNAs in serum of mice were found after PM2.5 exposure for 8 weeks. Among of them, 13 miRNAs related with lung cancer were consistent in serum and lung of mice. The target genes of 13 deregulated miRNAs including CRK, NR2F2, VIM, RASSF1, CCND2, PRKCA, SIRT1, CDK6, MAP3K7, HIF1A, UBE2V2, ATG10, BAX, E2F1, RASSF5 and CTNNB1, could involve in the pathway of lung cancer developing. Compared with the FA group, the significantly increases of histopathological changes, ROS and DNA damage were observed in lung of mice in CA group. Our study suggested that miRNAs in serum could be identified as candidate biomarkers to predict the lung cancer development during early PM2.5 exposure.

The Photochemistry on Space Station (PSS) Experiment: Organic Matter under Mars-like Surface UV Radiation Conditions in Low Earth Orbit.

The search for organic molecules at the surface of Mars is a top priority of the Mars Science Laboratory (NASA) and ExoMars 2020 (ESA) space missions. Their main goal is to search for past and/or present molecular compounds related to a potential prebiotic chemistry and/or a biological activity on the Red Planet. A key step to interpret their data is to characterize the preservation or the evolution of organic matter in the martian environmental conditions. Several laboratory experiments have been developed especially concerning the influence of ultraviolet (UV) radiation. However, the experimental UV sources do not perfectly reproduce the solar UV radiation reaching the surface of Mars. For this reason, the International Space Station (ISS) can be advantageously used to expose the same samples studied in the laboratory to UV radiation representative of martian conditions. Those laboratory simulations can be completed by experiments in low Earth orbit (LEO) outside the ISS. Our study was part of the Photochemistry on the Space Station experiment on board the EXPOSE-R2 facility that was kept outside the ISS from October 2014 to February 2016. Chrysene, adenine, and glycine, pure or deposited on an iron-rich amorphous mineral phase, were exposed to solar UV. The total duration of exposure to UV radiation is estimated to be in the 1250-1420 h range. Each sample was characterized prior to and after the flight by Fourier transform infrared (FTIR) spectroscopy. These measurements showed that all exposed samples were partially degraded. Their quantum efficiencies of photodecomposition were calculated in the 200-250 nm wavelength range. They range from 10-4 to 10-6 molecules·photon-1 for pure organic samples and from 10-2 to 10-5 molecules·photon-1 for organic samples shielded by the mineral phase. These results highlight that none of the tested organics are stable under LEO solar UV radiation conditions. The presence of an iron-rich mineral phase increases their degradation.

Comparing Treatment Acceptability and 12-Month Cessation Rates in Response to Web-Based Smoking Interventions Among Smokers Who Do and Do Not Screen Positive for Affective Disorders: Secondary Analysis.

BackgroundWeb-based cessation programs are now common for intervening with smokers. However, it remains unclear how acceptable or effective these interventions are among people with affective disorders and symptoms (ADS; eg, depression and anxiety). Research examining this is extremely limited, with mixed results on cessation rates. Additional large studies are needed to more fully understand whether Web-based interventions are similarly used and equally effective among people with and without affective disorder symptomology. If not, more targeted Web-based interventions may be required.ObjectiveThe goal of the research was to compare Web-based treatment acceptability (defined by satisfaction and use) and 12-month cessation outcomes between smokers with and without ADS.MethodsParticipants (N=2512) were adult smokers enrolled in a randomized, comparative effectiveness trial of two Web-based smoking interventions designed for the general population of smokers. At baseline, participants reported demographic and smoking characteristics and completed measures assessing ADS. Participants were then classified into subgroups based on their self-reported ADS—either into a no ADS group or into six nonmutually exclusive subgroups: depression, posttraumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and more than one ADS. Surveys at 12 months postrandomization included subjective ratings of treatment acceptability and self-reported smoking cessation. Treatment use (ie, number of log-ins and total duration of exposure) was assessed via automated records.ResultsRelative to the no ADS group, all six ADS subgroups reported significantly greater satisfaction with their assigned Web treatment program, but they spent less time logged in than those with no ADS. For number of log-ins, a treatment arm by ADS group interaction was observed across all ADS subgroups except GAD, suggesting that relative to the no ADS group, they logged in less to one website but not the other. At the 12-month follow-up, abstinence rates in the no ADS group (153/520, 29.42%) were significantly higher than for participants who screened positive for depression (306/1267, 24.15%; P=.03), PTSD (294/1215, 24.19%; P=.03), PD (229/1003, 23.83%; P=.009), and two or more ADS (323/1332, 24.25%; P=.03). Post hoc analyses suggest the lower quit rates may be associated with differences in baseline nicotine dependence and levels of commitment to resist smoking in difficult situations. Website use did not explain the differential abstinence rates.ConclusionsDespite reporting higher levels of treatment satisfaction, most smokers with ADS used their assigned intervention less often and had lower quit rates than smokers with no ADS at treatment onset. The results support the need for developing more targeted interventions for smokers with ADS.Trial registrationClinical Trials.gov NCT01812278; https://clinicaltrials.gov/ct2/show/NCT01812278 (Archived by WebCite at http://www.webcitation.org/78L9cNdG4)

Nonspecific stress response to temperature increase in Gammarus lacustris Sars with respect to oxygen-limited thermal tolerance concept.

The previously undescribed dynamics of the heat shock protein HSP70 and subsequent lipid peroxidation products have been assessed alongside lactate dehydrogenase activity for Gammarus lacustris Sars, an amphipod species from the saltwater Lake Shira (Republic of Khakassia). Individuals were exposed to a gradual temperature increase of 1 °C/hour (total exposure duration of 26 hours) starting from the mean annual temperature of their habitat (7 °C) up to 33 °C. A complex of biochemical reactions occurred when saltwater G. lactustris was exposed to the gradual changes in temperature. This was characterized by a decrease in lactate dehydrogenase activity and the launching of lipid peroxidation. The HSP70 level did not change significantly during the entire experiment. In agreement with the concept of oxygen-limited thermal tolerance, an accumulation of the most toxic lipid peroxides (triene conjugates and Schiff bases) in phospholipids occurred at the same time and temperature as the accumulation of lactate. The main criterion overriding the temperature threshold was, therefore, the transition to anaerobiosis, confirmed by the elevated lactate levels as observed in our previous associated study, and by the development of cellular stress, which was expressed by an accumulation of lipid peroxidation products. An earlier hypothesis, based on freshwater individuals of the same species, has been confirmed whereby the increased thermotolerance of G. lacustris from the saltwater lake was caused by differences in energy metabolism and energy supply of nonspecific cellular stress-response mechanisms. With the development of global climate change, these reactions could be advantageous for saltwater G. lacustris. The studied biochemical reactions can be used as biomarkers for the stress status of aquatic organisms when their habitat temperature changes.

Melanopsin-Driven Pupil Response and Light Exposure in Non-seasonal Major Depressive Disorder.

Background: Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) signal non-imaging forming effects of environmental light for circadian phoentrainment, the pupil light reflex, and mood regulation. In seasonal affective disorder, ipRGC dysfunction is thought to cause abberant transmission of the external illumination for photoentrainment. It is not known if patients with non-seasonal depression have abnormal melanospin mediated signaling and/or irregular environmental light exposure.Methods: Twenty-one adults who live in a sub-tropical region, including eight patients with non-seasonal depression and thirteen age-matched healthy controls were recruited. The Mini International Neuropsychiatry Interview diagnosed the presence of a major depressive disorder. Light exposure was determined using actigraphy over a 2 week period. The melanopsin mediated post-illumination pupil response (PIPR) and outer retinal inputs to ipRGCs (transient pupil response and maximum pupil constriction amplitude) were measured in response to 1 s, short and long wavelength light with high and low melanopsin excitation.Results: The mean daylight exposure as a function of clock hours and total light exposure duration (mins) to illumination levels commonly recommended for depression therapy were not significantly different between groups. Out of 84 pupil measurements (42 each in the depression and control groups), the melanopsin-mediated PIPR amplitude, transient pupil response, and pupil constriction amplitude were not significantly different between groups.Conclusions: This report provides initial evidence of normal melanopsin function and environmental light exposures in patients with pre-dominately mid and moderate non-seasonal depression in a subtropical location in the southern hemisphere.

Intermittent Exposure to Cigarette Smoke Increases Lung Tumors and the Severity of Emphysema More than Continuous Exposure.

Lung cancer and chronic obstructive pulmonary disease are leading causes of morbidity and mortality worldwide, and cigarette smoking is a main risk factor for both. The presence of emphysema, an irreversible lung disease, further raises the risk of lung cancer in patients with chronic obstructive pulmonary disease. The mechanisms involved in smoke-induced tumorigenesis and emphysema are not fully understood, attributable to a lack of appropriate animal models. Here, we optimized a model of cigarette smoke (CS)-induced lung cancer and emphysema in A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent carcinogen. We investigated whether variations in CS exposure patterns with the same total amount and duration of exposure affect tumorigenesis and/or development of emphysema. Continuous CS exposure for 3 months significantly suppressed 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced development of adenomas and adenocarcinomas; however, emphysema independently developed during this period. Surprisingly, intermittent CS exposure increased the severity of emphysema and resulted in a higher incidence of adenocarcinomas. Furthermore, intermittent CS exposure elicited a marked increase in M2-polarized macrophages within and near the developed tumors. By employing a CS exposure protocol with repeated cycles of cessation and relapse, we provide evidence that intermittent CS exposure enhances tumorigenesis and emphysema progression more than that of continuous CS exposure.

Frequency and duration of phototherapy in preterm infants &lt;35 weeks gestation

To evaluate the frequency, age at phototherapy (PT) initiation, and duration of PT use in infants 230/7 to 346/7 weeks of gestation in two neonatal intensive care units (NICUs) over 4 time periods. We reviewed the charts of all infants born at 230/7-346/7 weeks of gestational age (GA) and admitted to the NICUs of two hospitals between January 2009 and September 2015. We calculated the proportion of infants who received PT and the total duration of PT exposure. Overall 2023 (81.8%) received PT, and PT use was inversely related to GA and birthweight. More infants received PT when GA was added as a criterion for initiating PT. The median duration (interquartile range (IQR)) of PT for all infants was 50 (27-85) h and in the lowest GA group was 74 (42-111) h. Recent US consensus guidelines appear to have led to an increased use of PT in our NICUs and studies from Norway indicate that we use PT considerably more frequently and for longer durations than do our Norwegian colleagues.

Causal Effect of Lipids and Lipoproteins on Atherosclerosis

Mendelian randomization studies demonstrate that apolipoprotein B-containing lipoproteins have both causal and cumulative effects on the risk of atherosclerotic cardiovascular disease. The clinical benefit of lipid-lowering therapies depends on both the absolute reduction in circulating apolipoprotein B-containing lipoproteins and the total duration of exposure to these particles. Because atherosclerosis seems to be caused by the retention of apolipoprotein B-containing lipoproteins rather than by the cholesterol content carried by those lipoproteins, high-density lipoprotein-mediated efflux of cholesterol from the arterial wall may not reduce the risk of atherosclerotic cardiovascular disease.

Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study

People with major depressive disorder frequently exhibit increasing persistence of major depressive episodes. However, evidence for neuroprogression (ie, increasing brain pathology with longer duration of illness) is scarce. Microglial activation, which is an important component of neuroinflammation, is implicated in neuroprogression. We examined the relationship of translocator protein (TSPO) total distribution volume (VT), a marker of microglial activation, with duration of untreated major depressive disorder, and with total illness duration and antidepressant exposure. In this cross-sectional study, we recruited participants aged 18-75 years from the Toronto area and the Centre for Addiction and Mental Health (Toronto, ON, Canada). Participants either had major depressive episodes secondary to major depressive disorder or were healthy, as confirmed with a structured clinical interview and consultation with a study psychiatrist. To be enrolled, participants with major depressive episodes had to score a minimum of 17 on the 17-item Hamilton Depression Rating Scale, and had to be medication free or taking a stable dose of medication for at least 4 weeks before PET scanning. Eligible participants were non-smokers; had no history of or concurrent alcohol or substance dependence, neurological illness, autoimmune disorder, or severe medical problems; and were free from acute medical illnesses for the previous 2 weeks before PET scanning. Participants were excluded if they had used brain stimulation treatments within the 6 months before scanning, had used anti-inflammatory drugs lasting at least 1 week within the past month, were taking hormone replacement therapy, had psychotic symptoms, had bipolar disorder (type I or II) or borderline antisocial personality disorder, or were pregnant or breastfeeding. We scanned three primary grey-matter regions of interest (prefrontal cortex, anterior cingulate cortex, and insula) and 12 additional regions and subregions using 18F-FEPPA PET to measure TSPO VT. We investigated the duration of untreated major depressive disorder, and the combination of total duration of disease and duration of antidepressant treatment, as predictor variables of TSPO VT, assessing their significance. Between Sept 1, 2009, and July 6, 2017, we screened 134 participants for eligibility, of whom 81 were included in the study (current major depressive episode n=51, healthy n=30). We excluded one participant with a major depressive episode from the analysis because of unreliable information about previous medication use. Duration of untreated major depressive disorder was a strong predictor of TSPO VT (p<0·0001), as were total illness duration (p=0·0021) and duration of antidepressant exposure (p=0·037). The combination of these predictors accounted for about 50% of variance in TSPO VT in the prefrontal cortex, anterior cingulate cortex, and insula. In participants who had untreated major depressive disorder for 10 years or longer, TSPO VT was 29-33% greater in the prefrontal cortex, anterior cingulate cortex, and insula than in participants who were untreated for 9 years or less. TSPO VT was also 31-39% greater in the three primary grey-matter regions of participants with long duration of untreated major depressive disorder compared with healthy participants (p=0·00047). Microglial activation, as shown by TSPO VT, is greater in patients with chronologically advanced major depressive disorder with long periods of no antidepressant treatment than in patients with major depressive disorder with short periods of no antidepressant treatment, which is strongly suggestive of a different illness phase. Consistent with this, the yearly increase in microglial activation is no longer evident when antidepressant treatment is given. Canadian Institutes of Health Research and Neuroscience Catalyst Fund.