Sample records for background prolonged exposure

  1. Prolonged incubation and stacked film exposure improve sensitivity in western blotting.

    PubMed

    Luo, Haitao; Rankin, Gary O; Straley, Shannon; Chen, Yi Charlie

    2011-01-01

    Western blotting is a basic technique for protein detection. For proteins of less abundance or antibodies of poorer quality, an increased sensitivity is often desired. Although it is commonly known that higher concentrations of antibodies and prolonged film exposure times will help improve sensitivity in western blots, both measures come with their own risks, and it is often unclear to which extent these measures should be applied. We conducted time-course studies to investigate protein-antibody interactions and primary antibody-secondary antibody interactions in western blotting. We also propose a protocol of stacked film exposure and have tested it in standard curves and cancer cell samples. Our study found that protein-primary antibody interactions and primary antibody-secondary antibody interactions could take a longer time than commonly used "one hour" or "overnight", and in some cases longer than 48h, to reach its maximum binding. We also show that the modified protocol of stacked film exposure works well for both standard curves and biological samples, reaching a maximum sensitivity in western blots without blurring target signals or increasing backgrounds. In addition to regular optimization of antibody concentrations and film exposure time, a prolonged incubation with antibodies and stacked film exposure will also help improve sensitivity and reduce background in western blotting. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Prolonged Exposure: a Rapid Treatment for Phobias

    PubMed Central

    Watson, J. P.; Gaind, R.; Marks, I. M.

    1971-01-01

    Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

  3. Combined prolonged exposure therapy and paroxetine for PTSD related to the World Trade Center attack: a randomized controlled trial.

    PubMed

    Schneier, Franklin R; Neria, Yuval; Pavlicova, Martina; Hembree, Elizabeth; Suh, Eun Jung; Amsel, Lawrence; Marshall, Randall D

    2012-01-01

    Selective serotonin reuptake inhibitors (SSRIs) are often recommended in combination with established cognitive-behavioral therapies (CBTs) for posttraumatic stress disorder (PTSD), but combined initial treatment of PTSD has not been studied under controlled conditions. There are also few studies of either SSRIs or CBT in treating PTSD related to terrorism. The authors compared prolonged exposure therapy (a CBT) plus paroxetine (an SSRI) with prolonged exposure plus placebo in the treatment of terrorism-related PTSD. Adult survivors of the World Trade Center attack of September 11, 2001, with PTSD were randomly assigned to 10 weeks of treatment with prolonged exposure (10 sessions) plus paroxetine (N=19) or prolonged exposure plus placebo (N=18). After week 10, patients discontinued prolonged exposure and were offered 12 additional weeks of continued randomized treatment. Patients treated with prolonged exposure plus paroxetine experienced significantly greater improvement in PTSD symptoms (incidence rate ratio=0.50, 95% CI=0.30-0.85) and remission status (odds ratio=12.6, 95% CI=1.23-129) during 10 weeks of combined treatment than patients treated with prolonged exposure plus placebo. Response rate and quality of life were also significantly more improved with combined treatment. The subset of patients who continued randomized treatment for 12 additional weeks showed no group differences. Initial treatment with paroxetine plus prolonged exposure was more efficacious than prolonged exposure plus placebo for PTSD related to the World Trade Center attack. Combined treatment medication and prolonged exposure therapy deserves further study in larger samples with diverse forms of PTSD and over longer follow-up periods.

  4. Incorporating peer support during in vivo exposure to reverse dropout from prolonged exposure therapy for posttraumatic stress disorder: Clinical outcomes.

    PubMed

    Hernandez-Tejada, Melba A; Hamski, Stephanie; Sánchez-Carracedo, David

    2017-01-01

    Objective Prolonged exposure is characterized by reported dropout rates ranging from 25% to 40%. This premature attrition is also observed in other evidence-based treatments for posttraumatic stress disorder. While home-based telehealth delivery of prolonged exposure resolves logistical barriers to care such as travel time and cost, dropout appears unaffected. A previous study on dropouts from prolonged exposure delivered via telehealth found that Veterans, particularly those receiving care via telehealth, reported problems with in vivo exposure and that having a peer to offer support during in vivo exposure assignments might have prevented their attrition from treatment. Methods The present pilot study treatment was designed in a manner consistent with the aforementioned Veteran suggestions, specifically to involve peers offering verbal support and encouragement during in vivo exposure homework. Such a treatment modification might be particularly useful for those receiving care via telehealth, given increased difficulties with exposure reported when this treatment delivery modality is used. It was hypothesized that dropouts would agree to reengage in treatment with a peer and would subsequently evince improvement in posttraumatic stress disorder and depression scores as a result of this treatment reengagement. Results Of 82 dropouts from prolonged exposure, 29 reentered treatment when offered peer support during exposure (12 in telehealth and 17 in person). Conclusion Treatment reentry was effective insofar as indices of both posttraumatic stress disorder and depression were significantly reduced in both telehealth and in person groups, indicating that using peers in this way may be an effective means by which to return Veterans to care, and ultimately reduce symptomatology.

  5. Effectiveness of Cognitive Processing Therapy and Prolonged Exposure in the Department of Veterans Affairs.

    PubMed

    Rutt, Benjamin T; Oehlert, Mary E; Krieshok, Thomas S; Lichtenberg, James W

    2018-04-01

    Objective This study evaluated the effectiveness of cognitive processing therapy and prolonged exposure in conditions reflective of current clinical practice within the Veterans Health Administration. Method This study involved a retrospective review of 2030 charts. A total of 750 veterans from 10 U.S. states who received cognitive processing therapy or prolonged exposure in individual psychotherapy were included in the study (participants in cognitive processing therapy, N = 376; participants in prolonged exposure, N = 374). The main dependent variable was self-reported posttraumatic stress disorder symptoms as measured by total scores on the Posttraumatic Stress Disorder Checklist. The study used multilevel modeling to evaluate the absolute and relative effectiveness of both treatments and determine the relationship between patient-level variables and total Posttraumatic Stress Disorder Checklist scores during treatment. Results Cognitive processing therapy and prolonged exposure were equally effective at reducing total Posttraumatic Stress Disorder Checklist scores. Veterans who completed therapy reported significantly larger reductions in the Posttraumatic Stress Disorder Checklist than patients who did not complete therapy. There were no significant differences in the improvement of posttraumatic stress disorder symptoms with respect to age and three racial/ethnic groups (Caucasian, African American, and Hispanic). Conclusions Cognitive processing therapy and prolonged exposure were shown to be effective in conditions highly reflective of clinical practice and with a highly diverse sample of veterans. Challenges related to dropout from trauma focused therapy should continue to be researched.

  6. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells

    PubMed Central

    Browning, Cynthia L.; Qin, Qin; Kelly, Deborah F.; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria

    2016-01-01

    Abstract Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. PMID:27449664

  7. The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

    PubMed

    van de Griendt, Jolande M T M; van Dijk, Maarten K; Verdellen, Cara W J; Verbraak, Marc J P M

    2018-01-11

    Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

  8. Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

    PubMed

    Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

    2016-09-01

    Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Cardiac remodeling in preterm infants with prolonged exposure to a patent ductus arteriosus.

    PubMed

    de Waal, Koert; Phad, Nilkant; Collins, Nick; Boyle, Andrew

    2017-05-01

    Sustained volume load due to a patent ductus arteriosus (PDA) leads to cardiac remodeling. Remodeling changes can become pathological and are associated with cardiovascular disease progression. Data on remodeling changes in preterm infants is not available. Clinical and echocardiography data were collected in preterm infants <30 weeks gestation on postnatal day 3 and then every 7-14 days until closure of the ductus arteriosus. Images were analyzed using conventional techniques and speckle tracking. Remodeling changes of infants with prolonged (>14 days) exposure to a PDA were compared to control infants without a PDA. Thirty out of 189 infants had prolonged exposure to a PDA. The left heart remodeled to a larger and more spherical shape and thus significantly increased in volume. Most changes occurred in the first 4 weeks, plateaued, and then returned to control values. Systolic function and estimates of filling pressure increased and effective arterial elastance reduced with a PDA, however contractility was unchanged. Wall thickness increased after 4 weeks of increased volume exposure. The preterm PDA induces early and significant remodeling of the left heart. A compensated cardiac physiology was seen with preserved systolic function, suggesting adaptive rather than pathological remodeling changes with prolonged exposure to a PDA. © 2017 Wiley Periodicals, Inc.

  10. Prolonged exposure therapy for combat- and terror-related posttraumatic stress disorder: a randomized control comparison with treatment as usual.

    PubMed

    Nacasch, Nitzah; Foa, Edna B; Huppert, Jonathan D; Tzur, Dana; Fostick, Leah; Dinstein, Yula; Polliack, Michael; Zohar, Joseph

    2011-09-01

    Empirically based studies have demonstrated that prolonged exposure therapy effectively reduces posttraumatic stress disorder (PTSD) symptoms in a vast range of traumas, yet reports of the efficacy of such therapies in combat- and terror-related PTSD are scarce. In this article, we examine the efficacy of prolonged exposure therapy in combat- and terror-related PTSD in comparison to treatment as usual (TAU). Between July 2002 and October 2005, 30 patients of a trauma unit within a psychiatric outpatient clinic were recruited and randomized into prolonged exposure versus TAU therapies. Patients were diagnosed with chronic PTSD (Mini-International Neuropsychiatric Interview criteria) related to combat- (n = 19) or terror-related (n = 11) trauma. Main outcome measures included symptoms of PTSD and depression, as measured by the PTSD Symptom Scale-Interview Version and the Beck Depression Inventory. Posttraumatic stress disorder symptom severity was significantly lower in patients who received prolonged exposure therapy in comparison to patients who received TAU (F(1,24) = 35.3, P < .001). Similar results have emerged in measures of depression and state and trait anxiety. In addition, a significant change from pretreatment to follow-up was found for the prolonged exposure group (F(1,14) = 80.5, P < .0001), but not for the TAU group (F(1,10.3) = 0.6, P = .44). Findings indicate that, similar to PTSD related to other types of trauma, prolonged exposure therapy is beneficial in the amelioration of combat- and terror-related PTSD symptoms. In addition, prolonged exposure was superior to TAU in the short- and long-term reduction of PTSD and depression symptoms. clinicaltrials.gov Identifier: NCT00229372. © Copyright 2011 Physicians Postgraduate Press, Inc.

  11. A comparison of Narrative Exposure Therapy and Prolonged Exposure therapy for PTSD.

    PubMed

    Mørkved, N; Hartmann, K; Aarsheim, L M; Holen, D; Milde, A M; Bomyea, J; Thorp, S R

    2014-08-01

    The purpose of this review was to compare and contrast Prolonged Exposure (PE) and Narrative Exposure Therapy (NET). We examined the treatment manuals to describe the theoretical foundation, treatment components, and procedures, including the type, manner, and focus of exposure techniques and recording methods used. We examined extant clinical trials to investigate the range of treatment formats reported, populations studied, and clinical outcome data. Our search resulted in 32 studies on PE and 15 studies on NET. Consistent with prior reviews of PTSD treatment, it is evident that PE has a solid evidence base and its current status as a first line treatment for the populations studied to this date is warranted. We argue that NET may have advantages in treating complex traumatization seen in asylum seekers and refugees, and for this population NET should be considered a recommended treatment. NET and PE have several commonalities, and it is recommended that studies of these treatments include a broader range of populations and trauma types to expand the current knowledge on the treatment of PTSD. Published by Elsevier Ltd.

  12. Prolonged particulate chromate exposure does not inhibit homologous recombination repair in North Atlantic right whale (Eubalaena glacialis) lung cells.

    PubMed

    Browning, Cynthia L; Wise, Catherine F; Wise, John Pierce

    2017-09-15

    Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability. Thus, the goal of this study was to determine the effect of prolonged Cr(VI) exposure on HR repair and clastogenesis in North Atlantic right whale (Eubalaena glacialis) lung cells. We show particulate Cr(VI) induces HR repair activity after both acute (24h) and prolonged (120h) exposure in North Atlantic right whale cells. Although the RAD51 response was lower following prolonged Cr(VI) exposure compared to acute exposure, the response was sufficient for HR repair to occur. In accordance with active HR repair, no increase in Cr(VI)-induced clastogenesis was observed with increased exposure time. These results suggest prolonged Cr(VI) exposure affects HR repair and genomic stability differently in whale and human lung cells. Future investigation of the differences in how human and whale cells respond to chemical carcinogens may provide valuable insight into mechanisms of preventing chemical carcinogenesis. Copyright © 2017. Published by Elsevier Inc.

  13. Eating behaviours and attitudes following prolonged exposure to television among ethnic Fijian adolescent girls.

    PubMed

    Becker, Anne E; Burwell, Rebecca A; Gilman, Stephen E; Herzog, David B; Hamburg, Paul

    2002-06-01

    There are no published studies evaluating the impact of introduction of television on disordered eating in media-naïve populations. To assess the impact of novel, prolonged exposure to television on disordered eating attitudes and behaviours among ethnic Fijian adolescent girls. A prospective, multi-wave cross-sectional design was used to compare two samples of Fijian schoolgirls before and after prolonged regional television exposure with a modified 26-item eating attitudes test, supplemented with a semi-structured interview to confirm self-reported symptoms. Narrative data from a subset of respondents from the exposed sample were analysed for content relating television exposure to body image concerns. Key indicators of disordered eating were significantly more prevalent following exposure. Narrative data revealed subjects' interest in weight loss as a means of modelling themselves after television characters. This naturalistic experiment suggests a negative impact of television upon disordered eating attitudes and behaviours in a media-naïve population.

  14. Prolonged environmental exposure of arsenic through drinking water on the risk of hypertension and type 2 diabetes.

    PubMed

    Li, Xin; Li, Bing; Xi, Shuhua; Zheng, Quanmei; Lv, Xiuqiang; Sun, Guifan

    2013-11-01

    Prolonged exposure to inorganic arsenic has been a severe environmental public health issue worldwide in the recent decades. Increasing evidence has suggested a possible role of prolonged arsenic exposure through drinking water in the development of arsenic-induced chronic noncancer diseases, among which hypertension and type 2 diabetes (T2D) are the focus of concern. Although exposure to high levels of arsenic has been reported to be associated with excess risk of hypertension or T2D in a dose-dependent manner, the association has yet to be established, especially low-level exposure. This cross-sectional study was designed to evaluate the potential association between prolonged environmental arsenic exposure through drinking water and the prevalence of hypertension and T2D in Inner Mongolia, China, with emphasis on the assessment of low-level exposure. In this study (a total of 669 men and women), we found that the blood pressure levels were significantly correlated with cumulative arsenic exposure and that the systolic blood pressure of the subjects with arsenic exposure>50 μg/L was significantly higher than those of the subjects with <10 and 10-50 μg/L exposure. Significant prevalence of hypertension was found in the subjects of the >50 μg/L group both before and after adjustment for confounders. In addition, a significant negative relationship was found between urinary arsenic percentage of dimethylated arsenic (DMA%) and the prevalence of hypertension in the >50 μg/L group. However, low-level arsenic exposure (10-50 μg/L) was not statistically associated with hypertension. No significant difference of blood glucose was found among the groups with different arsenic exposure levels. No statistical association was found between arsenic exposure and T2D. Our findings suggested that prolonged arsenic exposure might play a role in the development of hypertension; however, only high-level arsenic was associated with the risk of hypertension. Our findings also

  15. Prolonged exposure to particulate chromate inhibits RAD51 nuclear import mediator proteins.

    PubMed

    Browning, Cynthia L; Wise, John Pierce

    2017-09-15

    Particulate hexavalent chromium (Cr(VI)) is a human lung carcinogen and a human health concern. The induction of structural chromosome instability is considered to be a driving mechanism of Cr(VI)-induced carcinogenesis. Homologous recombination repair protects against Cr(VI)-induced chromosome damage, due to its highly accurate repair of Cr(VI)-induced DNA double strand breaks. However, recent studies demonstrate Cr(VI) inhibits homologous recombination repair through the misregulation of RAD51. RAD51 is an essential protein in HR repair that facilitates the search for a homologous sequence. Recent studies show prolonged Cr(VI) exposure prevents proper RAD51 subcellular localization, causing it to accumulate in the cytoplasm. Since nuclear import of RAD51 is crucial to its function, this study investigated the effect of Cr(VI) on the RAD51 nuclear import mediators, RAD51C and BRCA2. We show acute (24h) Cr(VI) exposure induces the proper localization of RAD51C and BRCA2. In contrast, prolonged (120h) exposure increased the cytoplasmic localization of both proteins, although RAD51C localization was more severely impaired. These results correlate temporally with the previously reported Cr(VI)-induced RAD51 cytoplasmic accumulation. In addition, we found Cr(VI) does not inhibit interaction between RAD51 and its nuclear import mediators. Altogether, our results suggest prolonged Cr(VI) exposure inhibits the nuclear import of RAD51C, and to a lesser extent, BRCA2, which results in the cytoplasmic accumulation of RAD51. Cr(VI)-induced inhibition of nuclear import may play a key role in its carcinogenic mechanism since the nuclear import of many tumor suppressor proteins and DNA repair proteins is crucial to their function. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

    PubMed Central

    Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R.; Kuipers, Eline N.; Loef, Marieke; Zonneveld, Tom C. M.; Lucassen, Eliane A.; Sips, Hetty C. M.; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Meijer, Johanna H.; Coomans, Claudia P.; Biermasz, Nienke R.; Rensen, Patrick C. N.

    2015-01-01

    Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. PMID:25964318

  17. Demonstrating the Efficacy of Group Prolonged Exposure Treatment of PTSD in OEF/OIF/OND Male Veterans

    DTIC Science & Technology

    2015-12-01

    AWARD NUMBER: W81XWH-15-1-0005 TITLE: Demonstrating the Efficacy of Group Prolonged Exposure Treatment of PTSD in OEF/OIF/OND Male Veterans...in OEF/OIF/OND Male Veterans 5b. GRANT NUMBER W81XWH-15-1-0005 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Janet Kathreen C’de Baca 5d. PROJECT...format. The study population is male OEF/OIF/OND veterans who will be block randomized in groups of 3 into a 10-week, 90-minute, Prolonged Exposure

  18. Media Impacts on Women's Fertility Desires: A Prolonged Exposure Experiment.

    PubMed

    Knobloch-Westerwick, Silvia; Willis, Laura E; Kennard, Ashley R

    2016-06-01

    Media exposure may have implications for family planning, a public health issue of key importance. Drawing on social comparison theory and social identity theory, a prolonged exposure experiment examined whether media portrayals of women's social roles affect fertility desires among 166 American, nonstudent, never married, childless women ages 21-35 years old. After sign-up and baseline sessions, participants viewed magazine pages five days in a row. Stimuli presented women in either mother/homemaker roles, beauty ideal roles, or professional roles. Three days later, participants again indicated their number of desired children and time planned until first birth. Exposure to mother/homemaker and beauty ideal portrayals increased the number of desired children across time. Exposure to professional portrayals increased the time planned until 1st birth compared to beauty ideal portrayals-this impact was partially mediated by a shift toward more progressive gender norms (per social identity theory) and assimilation (per social comparison theory).

  19. Factors Contributing to Background Television Exposure in Low-Income Mexican-American Preschoolers.

    PubMed

    Thompson, Darcy A; Tschann, Jeanne M

    2016-09-01

    Objective Background television (TV) exposure is harmful to young children, yet few studies have focused on predictors of exposure. This study's objectives were to elucidate demographic, environmental, and behavioral correlates of background TV exposure in low-income Mexican-American preschoolers and to explore caregiver beliefs about the impact of such exposure. Methods A convenience sample of low-income Mexican-American female primary caregivers of preschoolers (3-5 years old, n = 309), recruited in safety-net clinics, were surveyed by phone. Caregivers reported the frequency of their child's exposure to background TV and responded to questions on the home media environment, TV use, and whether they had thought about background TV exposure and its impact on their child. Results Background TV exposure was common; 43 % reported that their child was often, very often, or always exposed to background TV. More hours of TV viewing by the caregiver and greater frequency of TV viewing during meals were associated with an increased frequency of exposure to background TV. Only 49 % of participants had ever thought about the impact of background TV. Believing that background TV is not harmful was associated with higher levels of background TV exposure. Conclusions Findings suggest that background TV exposure is frequent and caregiver awareness of its potential impact is low in low-income Mexican-American families. Beliefs that background TV is not harmful may predict risk of exposure. Potential targets for interventions focused on reducing background TV exposure in this population include increasing caregiver awareness of the potential negative impact of such TV exposure.

  20. Factors contributing to background television exposure in low-income Mexican American preschoolers

    PubMed Central

    Thompson, Darcy A.; Tschann, Jeanne M.

    2016-01-01

    Objective Background television (TV) exposure is harmful to young children, yet few studies have focused on predictors of exposure. This study’s objectives were to elucidate demographic, environmental, and behavioral correlates of background TV exposure in low-income Mexican American preschoolers and to explore caregiver beliefs about the impact of such exposure. Methods A convenience sample of low-income Mexican American female primary caregivers of preschoolers (3–5 years old, n=309), recruited in safety-net clinics, were surveyed by phone. Caregivers reported the frequency of their child’s exposure to background TV and responded to questions on the home media environment, TV use, and whether they had thought about background TV exposure and its impact on their child. Results Background TV exposure was common; 43% reported that their child was often, very often, or always exposed to background TV. More hours of TV viewing by the caregiver and greater frequency of TV viewing during meals were associated with an increased frequency of exposure to background TV. Only 49% of participants had ever thought about the impact of background TV. Believing that background TV is not harmful was associated with higher levels of background TV exposure. Conclusions Findings suggest that background TV exposure is frequent and caregiver awareness of its potential impact is low in low-income Mexican American families. Beliefs that background TV is not harmful may predict risk of exposure. Potential targets for interventions focused on reducing background TV exposure in this population include increasing caregiver awareness of the potential negative impact of such TV exposure. PMID:27007983

  1. Home cage locomotor changes in non-human primates after prolonged welding-fume exposure.

    PubMed

    Kim, Choong Yong; Sung, Jae Hyuck; Chung, Yong Hyun; Park, Jung Duck; Han, Jeong Hee; Lee, Jong Seong; Heo, Jeong Doo; Yu, Il Je

    2013-12-01

    To define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31 mg/m(3) total suspended particulate (TSP), 0.9 mg/m(3) of Mn), and high concentration (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of TSP. The monkeys were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day over 8 months in an inhalation chamber system equipped with an automatic fume generator. The home cage locomotor activity and patterns were determined using a camera system over 2-4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor activity of the high-concentration primates was found to be 5-6 times higher than that of the unexposed primates, and this increased locomotor activity was maintained for 7 weeks after ceasing the welding-fume exposure, eventually subsiding to three times higher after 13 weeks of recovery. Therefore, the present results, along with our previous observations of a high magnetic resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn concentration, indicate that prolonged welding-fume exposure can cause neurobehavioral changes in cynomolgus monkeys.

  2. The inoculating role of previous exposure to potentially traumatic life events on coping with prolonged exposure to rocket attacks: A lifespan perspective.

    PubMed

    Palgi, Yuval; Gelkopf, Marc; Berger, Rony

    2015-06-30

    Relatively little research have addressed the effect of prolonged exposure to rocket attacks with a lifespan perspective and only a handful of these studies focused on the effect of this exposure as a function of aging. The present study examined the effects of seven years of rocket attacks fired toward the south of Israel on adult participants of different ages. We examined whether potentially traumatic life events (PTLEs) unrelated to rocket attacks moderated the association between post-traumatic stress (PTS) symptoms and age. Data were obtained from a 2007 telephone survey using the Random Digit Dialing method and including 343 individuals (76.7% participation rate). Exposure to rockets, PTLEs, global distress, and post-traumatic symptomatology were assessed. Older age was associated with a higher level of PTS symptoms. Higher PTLE levels attenuated the association between age and PTS symptoms. Our results suggest that age is a risk factor for developing PTS symptoms under prolonged exposure to rocket attacks. However, previous levels of exposure to other negative events, as well as gender, appear to inoculate a person to stress, thus modulating the age-PTS association. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Prolonged Exposure versus Dynamic Therapy for Adolescent PTSD: A Pilot Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Gilboa-Schechtman, Eva; Foa, Edna B.; Shafran, Naama; Aderka, Idan M.; Powers, Mark B.; Rachamim, Lilach; Rosenbach, Lea; Yadin, Elna; Apter, Alan

    2010-01-01

    Objective: To examine the efficacy and maintenance of developmentally adapted prolonged exposure therapy for adolescents (PE-A) compared with active control time-limited dynamic therapy (TLDP-A) for decreasing posttraumatic and depressive symptoms in adolescent victims of single-event traumas. Method: Thirty-eight adolescents (12 to 18 years old)…

  4. Protection of the public in situations of prolonged radiation exposure. The application of the Commission's system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues.

    PubMed

    1999-01-01

    This report provides guidance on the application of the ICRP system of radiological protection to prolonged exposure situations affecting members of the public. It addresses the general application of the Commission's system to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations. Additionally, it provides recommendations on generic reference levels for such interventions. The report also considers some specific situations and discusses a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain radioactive substances. Annexes provide some examples of prolonged exposure situations and discuss the radiological protection quantities, radiation-induced health effects and aspects of the Commission's system of radiological protection relevant to prolonged exposure. Quantitative recommendations for prolonged exposures are provided in the report. They must be interpreted with extreme caution; Chapters 4 and 5 stress the upper bound nature of the following values: Generic reference levels for intervention, in terms of existing total annual doses, are given as < approximately 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and < approximately 10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary). Intervention exemption levels for commodities, especially building materials, are expressed as an additional annual dose of approximately 1

  5. Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wagner, Katie A.; Woodley, Christa M.; Seaburg, Adam

    While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na +, K +, Ca 2+, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were nomore » mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na +, Ca 2+, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na +, Ca 2+, K +, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.« less

  6. Prolonged continuous exposure to high fine particulate matter associated with cardiovascular and respiratory disease mortality in Beijing, China

    NASA Astrophysics Data System (ADS)

    Wang, Jinfeng; Yin, Qian; Tong, Shilu; Ren, Zhoupeng; Hu, Maogui; Zhang, Hongrui

    2017-11-01

    Although many studies examined the effects of fine particulate matter (PM2.5) on the deaths of cardiovascular disease (CVD) and respiratory disease (RD), few research has paid attention to the effects of prolonged continuous exposure to high PM2.5 pollution. This study estimated the excess risks (ER) of CVD and RD mortalities associated with prolonged continuous exposure to high PM2.5 pollution for the whole population and specific subsociodemographic groups in Beijing, which is the capital city of China with over 20 million residents and having severe PM2.5 pollution problems. Our results suggested that when high PM2.5 pollution occurred continuously, at various thresholds and durations, the adverse effects on CVD and RD mortalities varied significantly. The CVD mortality risks in association with prolonged continuous high PM2.5 pollution exposure were more serious for single individuals (including unmarried, divorced, and widowed), illiterate and outdoor workers than for other specific subsociodemographic groups. When the daily PM2.5 concentration higher than 105 μg/m3 consecutively occurs, at the ninth day, the ERs of CVD death for single individuals, illiterate and outdoor workers groups reached to 45% (95% CI: 22, 71), 51% (95% CI: 28, 79) and 53% (95% CI: 29, 82) respectively. On the other hand, prolonged continuous high PM2.5 pollution level appeared to contribute a higher proportion of RD deaths among illiterate and outdoor workers, but less significant for the other specific subsociodemographic groups. When the duration with daily PM2.5 pollution higher than 115 μg/m3 reached to six days, the ERs for outdoor workers and illiterate attributed to prolonged continuous PM2.5 pollution exposure increased 36% (95% CI: 5, 76) and 49% (95% CI: 16, 91) respectively.

  7. Physical Simulation of a Prolonged Plasma-Plume Exposure of a Space Debris Object

    NASA Astrophysics Data System (ADS)

    Shuvalov, V. A.; Gorev, N. B.; Tokmak, N. A.; Kochubei, G. S.

    2018-05-01

    A methodology has been developed for the physical (laboratory) simulation of the prolonged exposure of a space debris object to high-energy ions of a plasma plume for removing the object into low-Earth orbit with its subsequent burning in the Earth's atmosphere. The methodology is based on the equivalence criteria of two modes of exposure (in the Earth's ionosphere and in the setup) and the procedure for accelerated resource tests in terms of the sputtering of the space debris material and its deceleration by a plasma jet in the Earth's ionosphere.

  8. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

    ERIC Educational Resources Information Center

    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  9. Effects of prolonged exposure to perchlorate on thyroid and reproductive function in zebrafish

    USGS Publications Warehouse

    Mukhi, S.; Patino, R.

    2007-01-01

    The objectives of this study were to determine the effects of prolonged exposure to perchlorate on (1) thyroid status and reproductive performance of adult zebrafish (Danio rerio) and (2) F1 embryo survival and early larval development. Using a static-renewal procedure, mixed sex populations of adult zebrafish were exposed to 0, 10, and 100 mg/l nominal concentrations of waterborne perchlorate for 10 weeks. Thyroid histology was qualitatively assessed, and females and males were separated and further exposed to their respective treatments for six additional weeks. Eight females in each tank replicate (n = 3) were paired weekly with four males from the same respective treatment, and packed-egg (spawn) volume (PEV) was measured each of the last five weeks. At least once during weeks 14-16 of exposure, other end points measured included fertilization rate, fertilized egg diameter, hatching rate, standard length, and craniofacial development of 4-day-postfertilization larvae and thyroid hormone content of 3.5-h embryos and of exposed mothers. At 10 weeks of exposure, perchlorate at both concentrations caused thyroidal hypertrophy and colloid depletion. A marked reduction in PEV was observed toward the end of the 6-week spawning period, but fertilization and embryo hatching rates were unaffected. Fertilized egg diameter and larval length were increased by parental exposure to perchlorate. Larval head depth was unaffected but the forward protrusion of the lower jaw-associated cartilage complexes, Meckel's and ceratohyal, was decreased. Exposure to both concentrations of perchlorate inhibited whole-body thyroxine content in mothers and embryos, but triiodothyronine content was unchanged. In conclusion, prolonged exposure of adult zebrafish to perchlorate not only disrupts their thyroid endocrine system but also impairs reproduction and influences early F1 development. ?? 2007 Oxford University Press.

  10. Cognitive functions and cerebral oxygenation changes during acute and prolonged hypoxic exposure.

    PubMed

    Davranche, Karen; Casini, Laurence; Arnal, Pierrick J; Rupp, Thomas; Perrey, Stéphane; Verges, Samuel

    2016-10-01

    The present study aimed to assess specific cognitive processes (cognitive control and time perception) and hemodynamic correlates using functional near-infrared spectroscopy (fNIRS) during acute and prolonged high-altitude exposure. Eleven male subjects were transported via helicopter and dropped at 14 272 ft (4 350 meters) of altitude where they stayed for 4 days. Cognitive tasks, involving a conflict task and temporal bisection task, were performed at sea level the week before ascending to high altitude, the day of arrival (D0), the second (D2) and fourth (D4) day at high altitude. Cortical hemodynamic changes in the prefrontal cortex (PFC) area were monitored with fNIRS at rest and during the conflict task. Results showed that high altitude impacts information processing in terms of speed and accuracy. In the early hours of exposure (D0), participants displayed slower reaction times (RT) and decision errors were twice as high. While error rate for simple spontaneous responses remained twice that at sea level, the slow-down of RT was not detectable after 2 days at high-altitude. The larger fNIRS responses from D0 to D2 suggest that higher prefrontal activity partially counteracted cognitive performance decrements. Cognitive control, assessed through the build-up of a top-down response suppression mechanism, the early automatic response activation and the post-error adjustment were not impacted by hypoxia. However, during prolonged hypoxic exposure the temporal judgments were underestimated suggesting a slowdown of the internal clock. A decrease in cortical arousal level induced by hypoxia could consistently explain both the slowdown of the internal clock and the persistence of a higher number of errors after several days of exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Service utilization following participation in cognitive processing therapy or prolonged exposure therapy for post-traumatic stress disorder.

    PubMed

    Meyers, Laura L; Strom, Thad Q; Leskela, Jennie; Thuras, Paul; Kehle-Forbes, Shannon M; Curry, Kyle T

    2013-01-01

    This study evaluated the impact of a course of prolonged exposure or cognitive processing therapy on mental health and medical service utilization and health care service costs provided by the Department of Veterans Affairs (VA). Data on VA health service utilization and health care costs were obtained from national VA databases for 70 veterans who completed prolonged exposure or cognitive processing therapy at a Midwestern VA medical center. Utilization of services and cost data were examined for the year before and after treatment. Results demonstrated a significant decrease in the use of individual and group psychotherapy. Direct costs associated with mental health care decreased by 39.4%. Primary care and emergency department services remained unchanged.

  12. Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

    ERIC Educational Resources Information Center

    Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

  13. Training in the implementation of prolonged exposure therapy: provider correlates of treatment outcome.

    PubMed

    Eftekhari, Afsoon; Crowley, Jill J; Ruzek, Josef I; Garvert, Donn W; Karlin, Bradley E; Rosen, Craig S

    2015-02-01

    The authors examined the degree to which provider characteristics, such as profession, treatment orientation, prior experience in treating posttraumatic stress disorder (PTSD), prior experience with prolonged exposure (PE) therapy, and attitudes about PE, were related to the clinical outcomes of veterans receiving care from clinicians participating in the national Department of Veterans Affairs (VA) PE Training Program. Positive patient outcomes were achieved by providers of every profession, theoretical orientation, level of clinical experience treating PTSD, and prior PE training experience. With 1,105 providers and 32 predictors (13 provider variables), power was at least 90% power to detect an effect of β = .15. Profession was the only provider characteristic significantly related to outcomes, but the mean effect (a 2 point difference on the PTSD Checklist) was too small to be clinically meaningful. The results support the intensive training model used in the VA PE training program and demonstrate that clinicians of varying backgrounds can be trained using interactive training workshops followed by case consultation to deliver PE effectively. Published 2015. This article is a US Government work and is in the public domain in the USA.

  14. Response of Escherichia coli to Prolonged Berberine Exposure.

    PubMed

    Budeyri Gokgoz, Nilay; Avci, Fatma Gizem; Yoneten, Kubra Karaosmanoglu; Alaybeyoglu, Begum; Ozkirimli, Elif; Sayar, Nihat Alpagu; Kazan, Dilek; Sariyar Akbulut, Berna

    2017-07-01

    Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.

  15. Does virtual reality increase emotional engagement during exposure for PTSD? Subjective distress during prolonged and virtual reality exposure therapy.

    PubMed

    Reger, Greg M; Smolenski, Derek; Norr, Aaron; Katz, Andrea; Buck, Benjamin; Rothbaum, Barbara O

    2018-06-08

    Prolonged exposure (PE) is a treatment for posttraumatic stress disorder (PTSD) based on emotional processing theory. According to this theory, emotional engagement during imaginal exposure is critical to clinical outcome. One rationale for virtual reality exposure therapy (VRE) is the ability of trauma-relevant, multi-sensory stimuli to increase emotional engagement. This study compared the subjective distress of active duty soldiers (N = 108) during exposure via PE or VRE. Soldiers with higher mean or peak distress during the first imaginal exposure had higher baseline PTSD symptom severity. There was no difference between groups on average or peak distress during imaginal exposure at the first or final exposure session. There were no significant differences in between-session habituation observed between VRE and PE groups. However, each ten-point decrease in SUDS scores, either mean or peak, from the initiation of imaginal exposure to the end of treatment, was associated with a greater decrease in CAPS-W scores for both groups. There were no group differences in these trajectories or the magnitude of the association between distress/habituation, and PTSD symptoms. Future research on VRE should measure patient ratings of engagement during exposure to better understand which patients are aided by this innovative approach to treatment. Published by Elsevier Ltd.

  16. Prolonged Exposure for Guilt and Shame in a Veteran of Operation Iraqi Freedom

    PubMed Central

    Paul, Lisa A.; Gros, Daniel F.; Strachan, Martha; Worsham, Glenna; Foa, Edna B.; Acierno, Ron

    2014-01-01

    Morally injurious events appear capable of producing posttraumatic stress disorder (PTSD), even though they may not involve actual or perceived life-threat or a response of fear, horror, or helplessness. Researchers have questioned whether exposure therapies can address these events. The current report presents evidence of the effectiveness of this treatment approach for addressing posttraumatic symptoms related to a morally injurious event through an illustrative case of an Operation Iraqi Freedom veteran with PTSD characterized by symptoms of guilt and shame. The veteran was successfully treated with nine sessions of prolonged exposure therapy, reporting minimal PTSD symptoms one week post-treatment and at a six-month follow-up assessment. Implications for the treatment of veterans with significant guilt and shame using exposure-based therapies, and with respect to the recent changes to the diagnostic criteria for PTSD, are discussed. PMID:25505798

  17. Virtual reality exposure versus prolonged exposure for PTSD: Which treatment for whom?

    PubMed

    Norr, Aaron M; Smolenski, Derek J; Katz, Andrea C; Rizzo, Albert A; Rothbaum, Barbara O; Difede, JoAnn; Koenen-Woods, Patricia; Reger, Mark A; Reger, Greg M

    2018-06-01

    The majority of studies comparing active psychological treatments for posttraumatic stress disorder (PTSD) do not find significant differences at posttreatment. This was the case in a recent trial examining prolonged exposure (PE) and virtual reality exposure (VRE) among active-duty soldiers with combat-related PTSD. Matching individual patients to specific treatments provides a potential avenue to improve significantly the public health impact of effective treatments for PTSD. A composite moderator approach was used to identify profiles of patients who would see superior PTSD symptom reduction in VRE or PE to inform future treatment matching. Active duty U.S. army soldiers (N = 108) were enrolled in a randomized clinical trial comparing VRE and PE in the treatment of PTSD stemming from deployments to Iraq or Afghanistan. Eighteen baseline variables were examined to identify treatment response heterogeneity in two patient groups: those with a superior response to PE and those with a superior response to VRE. The final composite moderator comprised four of 18 baseline variables. Results revealed that patients who were predicted to see greater PTSD symptom reduction in VRE were likely to be younger, not taking antidepressant medication, had greater PTSD hyperarousal symptoms, and were more likely to have greater than minimal suicide risk. Results suggest that treatment matching based on patient profiles could meaningfully improve treatment efficacy for combat-related PTSD. Future research can build on these results to improve our understanding of how to improve treatment matching for PTSD. © 2018 Wiley Periodicals, Inc.

  18. Is Exposure Necessary? A Randomized Clinical Trial of Interpersonal Psychotherapy for PTSD

    PubMed Central

    Markowitz, John C.; Petkova, Eva; Neria, Yuval; Van Meter, Page E.; Zhao, Yihong; Hembree, Elizabeth; Lovell, Karina; Biyanova, Tatyana; Marshall, Randall D.

    2015-01-01

    Background Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). No treatment benefits all patients, however. We tested Interpersonal Psychotherapy, which has demonstrated antidepressant efficacy and showed promise in pilot PTSD research, as a non-exposure-based, non-cognitive behavioral PTSD treatment. Methods A randomized, fourteen-week trial compared Interpersonal Psychotherapy; Prolonged Exposure, an exposure-based exemplar; and Relaxation Therapy, an active control psychotherapy. Subjects were 110 unmedicated patients having DSM-IV chronic PTSD and Clinician-Administered PTSD Scale (CAPS) score >50. Randomization stratified for comorbid major depression. We hypothesized Interpersonal Psychotherapy would be no more than minimally inferior (CAPS difference <12.5 points) to Prolonged Exposure. Results All therapies had large within-group pre/post effect sizes (d=1.32–1.88). Response rates (>30% CAPS improvement) were: Interpersonal Psychotherapy 63%, Prolonged Exposure 47%, Relaxation Therapy 38% (n.s.). Interpersonal psychotherapy and Prolonged Exposure CAPS outcome differed by 5.5 points (n.s.); the null hypothesis of more than minimal Interpersonal Psychotherapy inferiority was rejected (p=0.035). Patients with comorbid major depression dropped out from Prolonged Exposure nine times more than non-depressed Prolonged Exposure patients. Interpersonal Psychotherapy and Prolonged Exposure improved quality of life and social functioning more than Relaxation Therapy. Conclusions This first controlled study of individual Interpersonal Psychotherapy for PTSD demonstrated non-inferiority to the “gold standard” PTSD treatment. Interpersonal Psychotherapy had (non-significantly) lower attrition and higher response rates than Prolonged Exposure. Contradicting a widespread clinical belief, PTSD treatment may not require cognitive behavioral exposure to trauma reminders. Moreover, as differential

  19. Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

    ERIC Educational Resources Information Center

    Hunter, John A.

    2010-01-01

    Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

  20. Direction of Influence between Posttraumatic and Depressive Symptoms during Prolonged Exposure Therapy among Children and Adolescents

    ERIC Educational Resources Information Center

    Aderka, Idan M.; Foa, Edna B.; Applebaum, Edna; Shafran, Naama; Gilboa-Schechtman, Eva

    2011-01-01

    Objective: Our objective in the present study was to examine the temporal sequencing of posttraumatic and depressive symptoms during prolonged exposure therapy for posttraumatic stress disorder (PTSD) among children and adolescents. Method: Participants were 73 children and adolescents (56.2% female) between the ages of 8 and 18. Participants…

  1. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    PubMed

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. Published by Oxford University Press on behalf of the

  2. Short and prolonged exposure to hyperglycaemia in human fibroblasts and endothelial cells: metabolic and osmotic effects.

    PubMed

    Moruzzi, Noah; Del Sole, Marianna; Fato, Romana; Gerdes, Jantje M; Berggren, Per-Olof; Bergamini, Christian; Brismar, Kerstin

    2014-08-01

    High blood glucose levels are the main feature of diabetes. However, the underlying mechanism linking high glucose concentration to diabetic complications is still not fully elucidated, particularly with regard to human physiology. Excess of glucose is likely to trigger a metabolic response depending on the cell features, activating deleterious pathways involved in the complications of diabetes. In this study, we aim to elucidate how acute and prolonged hyperglycaemia alters the biology and metabolism in human fibroblasts and endothelial cells. We found that hyperglycaemia triggers a metabolic switch from oxidative phosphorylation to glycolysis that is maintained over prolonged time. Moreover, osmotic pressure is a major factor in the early metabolic response, decreasing both mitochondrial transmembrane potential and cellular proliferation. After prolonged exposure to hyperglycaemia we observed decreased mitochondrial steady-state and uncoupled respiration, together with a reduced ATP/ADP ratio. At the same time, we could not detect major changes in mitochondrial transmembrane potential and reactive oxygen species. We suggest that the physiological and metabolic alterations observed in healthy human primary fibroblasts and endothelial cells are an adaptive response to hyperglycaemia. The severity of metabolic and bioenergetics impairment associated with diabetic complications may occur after longer glucose exposure or due to interactions with cell types more sensitive to hyperglycaemia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. [Effects of exposure frequency and background information on preferences for photographs of cars in different locations].

    PubMed

    Matsuda, Ken; Kusumi, Takashi; Hosomi, Naohiro; Osa, Atsushi; Miike, Hidetoshi

    2014-08-01

    This study examined the influence of familiarity and novelty on the mere exposure effect while manipulating the presentation of background information. We selected presentation stimuli that integrated cars and backgrounds based on the results of pilot studies. During the exposure phase, we displayed the stimuli successively for 3 seconds, manipulating the background information (same or different backgrounds with each presentation) and exposure frequency (3, 6, and 9 times). In the judgment phase, 18 participants judged the cars in terms of preference, familiarity, and novelty on a 7-point scale. As the number of stimulus presentations increased, the preference for the cars increased during the different background condition and decreased during the same background condition. This increased preference may be due to the increase in familiarity caused by the higher exposure frequency and novelty resulting from the background changes per exposure session. The rise in preference judgments was not seen when cars and backgrounds were presented independently. Therefore, the addition of novel features to each exposure session facilitated the mere exposure effect.

  4. Media exposure and prolonged grief: A study of bereaved parents and siblings after the 2011 Utøya Island terror attack.

    PubMed

    Kristensen, Pål; Dyregrov, Kari; Dyregrov, Atle; Heir, Trond

    2016-11-01

    After terror attacks, the media coverage can be a potential secondary stressor for bereaved families. In the present study, we aimed to examine the level of prolonged grief (PG), and to explore the association between media exposure and PG in parents and siblings of individuals who were killed in a terror attack. Parents and siblings (n = 103) from 42 different families bereaved by the 2011 Utøya Island mass shooting participated in a survey 18 months after the attack. The survey measured the amount of media exposure experienced by the bereaved during the first month after the attack. PG was self-reported using the Inventory of Complicated Grief (ICG). Data was analyzed with multilevel methods with mixed effects models. Of the total sample of participants, 78.6% (n = 81/103) had sum scores higher than the designated cutoff >25 on ICG, indicating a probable prolonged grief disorder (PGD). Multilevel analysis showed significantly higher level of PG among those who reported high exposure to the media coverage (>4 hours daily) the first month after the attack, among females, and among those who were in contact with their son/daughter/brother/sister by telephone during the attack. With the cross-sectional design, caution should be taken about making interpretations about causal effects. Media exposure may trigger or maintain prolonged grief reactions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors

    PubMed Central

    Mo, Irene Fung Ying; Yip, Kevin Hak Kong; Chan, Wing Keung; Law, Helen Ka Wai; Lau, Yu Lung; Chan, Godfrey Chi Fung

    2008-01-01

    Background Human mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are multipotent cells with potential therapeutic value. Owing to their osteogenic capability, MSCs may be clinically applied for facilitating osseointegration in dental implants or orthopedic repair of bony defect. However, whether wound infection or oral microflora may interfere with the growth and osteogenic differentiation of human MSCs remains unknown. This study investigated whether proliferation and osteogenic differentiation of MSCs would be affected by potent gram-positive and gram-negative derived bacterial toxins commonly found in human settings. Results We selected lipopolysaccharide (LPS) from Escherichia coli and lipoteichoic acid (LTA) from Streptococcus pyogenes as our toxins of choice. Our findings showed both LPS and LTA did not affect MSC proliferation, but prolonged LPS challenge upregulated the osteogenic differentiation of MSCs, as assessed by alkaline phosphatase activity and calcium deposition. Because toll-like receptors (TLRs), in particularly TLR4 and TLR2, are important for the cellular responsiveness to LPS and LTA respectively, we evaluated their expression profiles serially from MSCs to osteoblasts by quantitative PCR. We found that during osteogenic differentiation, MSC-derived osteoprogenitors gradually expressed TLR2 and TLR4 by Day 12. But under prolonged incubation with LPS, MSC-derived osteoprogenitors had reduced TLR2 and TLR4 gene expression. This peculiar response to LPS suggests a possible adaptive mechanism when MSCs are subjected to continuous exposure with bacteria. Conclusion In conclusion, our findings support the potential of using human MSCs as a biological graft, even under a bacterial toxin-rich environment. PMID:18799018

  6. Effects of prolonged exposure to space flight factors for 175 days on lettuce seeds

    NASA Astrophysics Data System (ADS)

    Nevzgodina, L. V.; Maximova, E. N.; Akatov, Yu. A.

    We have studied the effects of prolonged (up to 175 days) exposure of Lactuca sativa seeds to space flight factors, including primary cosmic radiation heavy ions. The data obtained evidence a significant fourfold increase ofs pontaneous mutagenesis in seeds both with regard to the total number of aberrant cells as well as the formation of single cells with multiple aberrations. Comparison of the present experiment with earlier works shows that the frequency of such aberrations increases with the duration of the flight.

  7. Distinguishing nanomaterial particles from background airborne particulate matter for quantitative exposure assessment

    NASA Astrophysics Data System (ADS)

    Ono-Ogasawara, Mariko; Serita, Fumio; Takaya, Mitsutoshi

    2009-10-01

    As the production of engineered nanomaterials quantitatively expands, the chance that workers involved in the manufacturing process will be exposed to nanoparticles also increases. A risk management system is needed for workplaces in the nanomaterial industry based on the precautionary principle. One of the problems in the risk management system is difficulty of exposure assessment. In this article, examples of exposure assessment in nanomaterial industries are reviewed with a focus on distinguishing engineered nanomaterial particles from background nanoparticles in workplace atmosphere. An approach by JNIOSH (Japan National Institute of Occupational Safety and Health) to quantitatively measure exposure to carbonaceous nanomaterials is also introduced. In addition to real-time measurements and qualitative analysis by electron microscopy, quantitative chemical analysis is necessary for quantitatively assessing exposure to nanomaterials. Chemical analysis is suitable for quantitative exposure measurement especially at facilities with high levels of background NPs.

  8. Combining group-based exposure therapy with prolonged exposure to treat U.S. Vietnam veterans with PTSD: a case study.

    PubMed

    Ready, David J; Vega, Edward M; Worley, Virginia; Bradley, Bekh

    2012-10-01

    Group-based exposure therapy (GBET) of 16-week duration was developed to treat combat-related posttraumatic stress disorder (PTSD) and decreased PTSD symptoms in 3 noncontrolled open trials with low attrition (0%-5%). Group-based exposure therapy has not produced as much PTSD symptom reduction as Prolonged Exposure (PE) within a U.S. Veterans Affairs PTSD treatment program, although PE had more dropouts (20%). This pilot study was of a model that combined key elements of GBET with components of PE in an effort to increase the effectiveness of a group-based treatment while reducing its length and maintaining low attrition. Twice per week, 8 Vietnam combat veterans with PTSD were treated for 12 weeks, with an intervention that included 2 within-group war trauma presentations per participant, 6 PE style individual imaginal exposure (IE) sessions per participant, daily listening to recorded IE sessions, and daily in vivo exposure exercises. All completed treatment and showed Significant reductions on all measures of PTSD with large effect sizes; 7 participants no longer met PTSD criteria on treating clinician administered interviews and a self-report measure at posttreatment. Significant reductions in depression with large effect sizes and moderate reductions in PTSD-related cognitions were also found. Most gains were maintained 6 months posttreatment. Published 2012. This article is a US Government work and is in the public domain in the USA.

  9. Emotional attentional control predicts changes in diurnal cortisol secretion following exposure to a prolonged psychosocial stressor.

    PubMed

    Lenaert, Bert; Barry, Tom J; Schruers, Koen; Vervliet, Bram; Hermans, Dirk

    2016-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been associated with several psychological disorders. Hence, the identification of individual difference variables that predict variations in HPA-axis activity represents an important challenge for psychiatric research. We investigated whether self-reported attentional control in emotionally demanding situations prospectively predicted changes in diurnal salivary cortisol secretion following exposure to a prolonged psychosocial stressor. Low ability to voluntarily control attention has previously been associated with anxiety and depressive symptomatology. Attentional control was assessed using the Emotional Attentional Control Scale. In students who were preparing for academic examination, salivary cortisol was assessed before (time 1) and after (time 2) examination. Results showed that lower levels of self-reported emotional attentional control at time 1 (N=90) predicted higher absolute diurnal cortisol secretion and a slower decline in cortisol throughout the day at time 2 (N=71). Difficulty controlling attention during emotional experiences may lead to chronic HPA-axis hyperactivity after prolonged exposure to stress. These results indicate that screening for individual differences may foster prediction of HPA-axis disturbances, paving the way for targeted disorder prevention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Effects of Systematic Cue Exposure Through Virtual Reality on Cigarette Craving

    PubMed Central

    Pericot-Valverde, Irene; Secades-Villa, Roberto; Gutiérrez-Maldonado, José

    2014-01-01

    Introduction: Cigarette cravings have been associated with less successful attempts to quit smoking and a greater likelihood of relapse after smoking cessation. Background craving refers to a relatively steady and continuous experience of craving, while cue-induced craving refers to phases of intense craving triggered by cues associated with smoking. Cue exposure treatment (CET) involves repeated exposure to stimuli associated with substance use in order to reduce craving responses. However, mixed results have been found regarding the effect of CET on both types of craving. The aim of this study was to assess the effect of systematic virtual reality cue exposure treatment (VR-CET) on background and cue-induced cravings. Methods: Participants were 48 treatment-seeking smokers. The VR-CET consisted of prolonged exposure sessions to several interactive virtual environments. The VR-CET was applied once a week over 5 weeks. An individualized hierarchy of exposure was drawn up for each patient starting from the easiest virtual environment. Background and cue-induced cravings were recorded in each session. Results: Cue-induced craving decreased over each session as a result of prolonged exposure. VR-CET also reduced cue-induced and background cravings across the 5 sessions, showing a cumulative effect across the exposure sessions. Conclusions: Our results evidenced the utility of VR-CET in reducing both types of cigarette craving. A combination of CET through VR with psychological treatments may improve current treatments for smoking cessation. PMID:24962558

  11. Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C.

    PubMed

    Vita, Marina F; Nagachar, Nivedita; Avramidis, Dimitrios; Delwar, Zahid M; Cruz, Mabel H; Siden, Åke; Paulsson, Kajsa M; Yakisich, Juan Sebastian

    2011-12-01

    Menadione (Vitamin K3) has anti-tumoral effects against a wide range of cancer cells. Its potential toxicity to normal cells and narrow therapeutic range limit its use as single agent but in combination with radiation or other anti-neoplastic agents can be of therapeutic use. In this paper, we first evaluated the early (within 3 h) effect of menadione on ongoing DNA replication. In normal rat cerebral cortex mini-units menadione showed an age dependent anti-proliferative effect. In tissue mini-units prepared from newborn rats, menadione inhibited ongoing DNA replication with an IC (50) of approximately 10 μM but 50 μM had no effect on mini-units from prepared adult rat tissue. The effect of short (72 h) and prolonged exposure (1-2 weeks) to menadione alone in the DBTRG.05MG human glioma cells line and in combination with vitamin C was studied. After short period of exposure data show that menadione alone or in combination with vitamin C provided similar concentration-response curves (and IC(50) values). Prolonged exposure to these drugs was evaluated by their ability to kill 100% of glioma cells and prevent regrowth when cells are re-incubated in drug-free media. In this long-term assay, menadione:vitamin C at a ratio 1:100 showed higher anti-proliferative activity when compared to each drug alone and allowed to reduce each drug concentration between 2.5 to 5-fold. Similar anti-proliferative effect was demonstrated in 8 patient derived glioblastoma cell cultures. Our data should be able to encourage further advanced studies on animal models to evaluate the potential use of this combination therapy for glioma treatment.

  12. Clinician perceptions of using a smartphone app with prolonged exposure therapy.

    PubMed

    Kuhn, Eric; Eftekhari, Afsoon; Hoffman, Julia E; Crowley, Jill J; Ramsey, Kelly M; Reger, Greg M; Ruzek, Josef I

    2014-11-01

    Clinician perceptions of clinical innovations affect their adoption and spread. This study investigated mental health clinicians' (n = 163) perceptions of a patient-facing smartphone application (app) for prolonged exposure (PE) therapy for posttraumatic stress disorder, before its public release. After reading a description of the app, participants rated perceptions of it based on diffusion of innovations theory constructs. Perceptions were generally favorable regarding the app's relative advantage over existing PE practices, compatibility with their values and needs, and complexity. Age (<40 years), smartphone ownership, and having used apps in care related to more favorable perceptions. Smartphone ownership, relative advantage, and complexity significantly predicted intention to use the app if it were available. These findings suggest that clinicians are receptive to using a PE app and that dissemination efforts should target sub-groups of PE clinicians to maximize adoption.

  13. The effect of prolonged exposure to 750 C air on the tribological performance of PM212

    NASA Technical Reports Server (NTRS)

    Bemis, Kirk; Bogdanski, Michael S.; Dellacorte, Christopher; Sliney, Harold E.

    1994-01-01

    The effect of prolonged exposure to 750 C air on the tribological performance and dimensional stability of PM212, a high temperature, self-lubricating composite, is studied. PM212, by weight, contains 70 percent metal-bonded Cr3C2, 15 percent BaF2/CaF2 eutectic, and 15 percent silver. Rub blocks were fabricated from PM212 by cold isostatic pressing followed by sintering. Prior to tribo-testing, the rub blocks were exposed to 750 C air for periods ranging from 100 to 1000 hours. Then, the rub blocks were slid against nickel-based superalloy disks in a double-rub-block tribometer in air under a 66 N load at temperatures from 25 to 750 C with a sliding velocity of 0.36 m/s. Unexposed rub blocks were tested for baseline comparison. Friction coefficients ranged from 0.24 to 0.37 for the unexposed rub blocks and from 0.32 to 0.56 for the exposed ones. Wear for both the composite blocks and superalloy disks was typically in the moderate to low range of 10(exp -5) to 10(exp -6) mm(exp 3)/N-m. Friction and wear data were similar for the rub blocks exposed for 100, 500, and 1000 hours. Prolonged exposure to 750 C air increased friction and wear of the PM212 rub blocks at room temperature, but their triboperformance remained unaffected at higher temperatures, probably due to the formation of lubricious metal oxides. Dimensional stability of the composite was studied by exposing specimens of varying thicknesses for 500 hours in air at 750 C. Block thicknesses were found to increase with increased exposure time until steady state was reached after 100 hours of exposure, probably due to oxidation.

  14. Effects of systematic cue exposure through virtual reality on cigarette craving.

    PubMed

    Pericot-Valverde, Irene; Secades-Villa, Roberto; Gutiérrez-Maldonado, José; García-Rodríguez, Olaya

    2014-11-01

    Cigarette cravings have been associated with less successful attempts to quit smoking and a greater likelihood of relapse after smoking cessation. Background craving refers to a relatively steady and continuous experience of craving, while cue-induced craving refers to phases of intense craving triggered by cues associated with smoking. Cue exposure treatment (CET) involves repeated exposure to stimuli associated with substance use in order to reduce craving responses. However, mixed results have been found regarding the effect of CET on both types of craving. The aim of this study was to assess the effect of systematic virtual reality cue exposure treatment (VR-CET) on background and cue-induced cravings. Participants were 48 treatment-seeking smokers. The VR-CET consisted of prolonged exposure sessions to several interactive virtual environments. The VR-CET was applied once a week over 5 weeks. An individualized hierarchy of exposure was drawn up for each patient starting from the easiest virtual environment. Background and cue-induced cravings were recorded in each session. Cue-induced craving decreased over each session as a result of prolonged exposure. VR-CET also reduced cue-induced and background cravings across the 5 sessions, showing a cumulative effect across the exposure sessions. Our results evidenced the utility of VR-CET in reducing both types of cigarette craving. A combination of CET through VR with psychological treatments may improve current treatments for smoking cessation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Predicting QT prolongation in humans during early drug development using hERG inhibition and an anaesthetized guinea-pig model

    PubMed Central

    Yao, X; Anderson, D L; Ross, S A; Lang, D G; Desai, B Z; Cooper, D C; Wheelan, P; McIntyre, M S; Bergquist, M L; MacKenzie, K I; Becherer, J D; Hashim, M A

    2008-01-01

    Background and purpose: Drug-induced prolongation of the QT interval can lead to torsade de pointes, a life-threatening ventricular arrhythmia. Finding appropriate assays from among the plethora of options available to predict reliably this serious adverse effect in humans remains a challenging issue for the discovery and development of drugs. The purpose of the present study was to develop and verify a reliable and relatively simple approach for assessing, during preclinical development, the propensity of drugs to prolong the QT interval in humans. Experimental approach: Sixteen marketed drugs from various pharmacological classes with a known incidence—or lack thereof—of QT prolongation in humans were examined in hERG (human ether a-go-go-related gene) patch-clamp assay and an anaesthetized guinea-pig assay for QT prolongation using specific protocols. Drug concentrations in perfusates from hERG assays and plasma samples from guinea-pigs were determined using liquid chromatography-mass spectrometry. Key results: Various pharmacological agents that inhibit hERG currents prolong the QT interval in anaesthetized guinea-pigs in a manner similar to that seen in humans and at comparable drug exposures. Several compounds not associated with QT prolongation in humans failed to prolong the QT interval in this model. Conclusions and implications: Analysis of hERG inhibitory potency in conjunction with drug exposures and QT interval measurements in anaesthetized guinea-pigs can reliably predict, during preclinical drug development, the risk of human QT prolongation. A strategy is proposed for mitigating the risk of QT prolongation of new chemical entities during early lead optimization. PMID:18587422

  16. Integrating Dialectical Behavior Therapy and Prolonged Exposure to Treat Co-Occurring Borderline Personality Disorder and PTSD: Two Case Studies

    ERIC Educational Resources Information Center

    Harned, Melanie S.; Linehan, Marsha M.

    2008-01-01

    Despite the high rate of trauma and PTSD among individuals with borderline personality disorder (BPD), no studies have specifically evaluated the treatment of PTSD in a BPD population. These case studies illustrate the use of a protocol based on prolonged exposure therapy that can be integrated into standard dialectical behavior therapy to treat…

  17. Effects of prolonged light exposure times on water sorption, solubility and cross-linking density of simplified etch-and-rinse adhesives.

    PubMed

    Wambier, Letícia; Malaquias, Tamirez; Wambier, Denise Stadler; Patzlaff, Rafael T; Bauer, José; Loguercio, Alessandro D; Reis, Alessandra

    2014-06-01

    This study evaluated the effects of light exposure times on water sorption, solubility, and polymer cross-linking density of simplified etch-and-rinse adhesives. Four commercial adhesives (XP Bond, Adper Single Bond 2, Tetric N-Bond, and Ambar) were selected, and resin disks 5 mm in diameter and 1.0 mm thick were prepared and light cured for 20, 40, or 80 s using an LED light-curing unit at 1200 mW/cm2. Water sorption and solubility were evaluated over a 28-day period. For polymer cross-linking density, additional specimens were prepared and their Knoop hardness measured before and after immersion in 100% ethanol. The data from each test were evaluated using a two-way ANOVA and Tukey's test (α = 0.05). The XP Bond adhesive showed higher water sorption (similar to Adper Single Bond 2) and solubility (p < 0.05) than did the other materials. Prolonged exposure times did not reduce the water sorption but did reduce the solubility of all tested materials (p < 0.05). For Ambar, the increase in the exposure time resulted in a significantly lower percent reduction in hardness. Water sorption, solubility, and cross-linking density of the materials selected in this study seem to be mainly influenced by the adhesive composition. Prolonged light exposure times reduced the solubility of the materials.

  18. Prolonged intrahepatic cholestasis after exposure to loxoprofen.

    PubMed

    Ichikawa, Takeshi; Sato, Hiroko; Kaira, Kyoichi; Oh-I, Shinsuke; Kakizaki, Satoru; Sato, Ken; Takagi, Hitoshi; Mori, Masatomo

    2008-12-01

    The objective of this report was to describe a case of prolonged intrahepatic cholestasis likely associated with the use of loxoprofen, a phenylpropionate NSAID. A 36-year-old female patient was transferred to Gunma University Hospital, Maebashi, Japan, with progressive pruritus and jaundice that developed after 5-day treatment with 120 mg/d of loxoprofen (maximum recommended dose, 180 mg/d) for menstrual pain. Liver function tests found the following concentrations: total bilirubin, 27.5 mg/dL (normal [nl] range, 0.3-1.2 mg/dL); aspartate aminotransferase, 151 IU/L (nl, 13-33 IU/L); alkaine aminotransferase, 470 IU/L (nl, 8-42 IU/L); alkaline phosphatase, 1082 IU/L (n1, 115-359 IUAL); and gamma-glutamyl transpeptidase, 795 IU/L (nl, 10-47 IU/L) indicative of intrahepatic cholestasis. No use of alcohol or other drugs or herbal products was reported. The patient had a history of elevated hepatic enzymes of unknown origin following the use of mefenamic acid. The patient was prescribed ursodeoxycholic acid 3 weeks after the onset of symptoms of intrahepatic cholestasis. Thereafter, due to progressive cholestasis, an IV pulse of methylprednisolone (1000 mg/d) and the herbal product Inchin-ko-to (TJ-135) were administered. Plasma bilirubin adsorption (PA) and plasma exchange (PE) were performed. Following treatment with PA and PE for 3 weeks with administration of methylprednisolone and Inchin-ko-to, signs and symptoms of intrahepatic cholestasis began to resolve (3.5 months after the onset); they were completely resolved 8 months after the initial episode. A Naranjo scale score of 6 suggested that loxoprofen was likely the cause of the prolonged cholestasis in this patient. Based on the Naranjo score, this case of prolonged intrahepatic cholestasis in a young woman was likely associated with loxoprofen use.

  19. Improving PTSD Outcomes in OIF/OEF Returnees: A Randomized Clinical Trial of Hydrocortisone Augmentation of Prolonged Exposure Therapy

    DTIC Science & Technology

    2012-08-01

    Melissa D . Altman, PhD will ensure that the ratings are accomplished in a reasonable time frame, and make the results available to the PI and co...Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report. European Journal of Traumatology. 2010(1): 5643. d . Solutions to...Brief Assessment of Cognition in Schizophrenia (BACS): Symbol-Coding Category Fluency: Animal Naming Trail Making Test: Part A Timed paper

  20. Previous Repeated Exposure to Food Limitation Enables Rats to Spare Lipid Stores during Prolonged Starvation.

    PubMed

    McCue, Marshall D; Albach, Audrey; Salazar, Giovanni

    The risk of food limitation and, ultimately, starvation dates back to the dawn of heterotrophy in animals, yet starvation remains a major factor in the regulation of modern animal populations. Researchers studying starvation more than a century ago suggested that animals subjected to sublethal periods of food limitation are somehow more tolerant of subsequent starvation events. This possibility has received little attention over the past decades, yet it is highly relevant to modern science for two reasons. First, animals in natural populations are likely to be exposed to bouts of food limitation once or more before they face prolonged starvation, during which the risk of mortality becomes imminent. Second, our current approach to studying starvation physiology in the laboratory focuses on nourished animals with no previous exposure to nutritional stress. We examined the relationship between previous exposure to food limitation and potentially adaptive physiological responses to starvation in adult rats and found several significant differences. On two occasions, rats were fasted until they lost 20% of their body mass maintained lower body temperatures, and had presumably lower energy requirements when subjected to prolonged starvation than their naive cohort that never experienced food limitation. These rats that were trained in starvation also had lower plasma glucose set -points and reduced their reliance on endogenous lipid oxidation. These findings underscore (1) the need for biologists to revisit the classic hypothesis that animals can become habituated to starvation, using a modern set of research tools; and (2) the need to design controlled experiments of starvation physiology that more closely resemble the dynamic nature of food availability.

  1. Unusual Versatility of the Filamentous, Diazotrophic Cyanobacterium Anabaena torulosa Revealed for Its Survival during Prolonged Uranium Exposure

    PubMed Central

    Chandwadkar, Pallavi; Nayak, Chandrani

    2017-01-01

    ABSTRACT Reports on interactions between cyanobacteria and uranyl carbonate are rare. Here, we present an interesting succession of the metabolic responses employed by a marine, filamentous, diazotrophic cyanobacterium, Anabaena torulosa for its survival following prolonged exposure to uranyl carbonate extending up to 384 h at pH 7.8 under phosphate-limited conditions. The cells sequestered uranium (U) within polyphosphates on initial exposure to 100 μM uranyl carbonate for 24 to 28 h. Further incubation until 120 h resulted in (i) significant degradation of cellular polyphosphates causing extensive chlorosis and cell lysis, (ii) akinete differentiation followed by (iii) extracellular uranyl precipitation. X-ray diffraction (XRD) analysis, fluorescence spectroscopy, X-ray absorption near edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) spectroscopy established the identity of the bioprecipitated uranium as a U(VI) autunite-type mineral, which settled at the bottom of the vessel. Surprisingly, A. torulosa cells resurfaced as small green flakes typical of actively growing colonies on top of the test solutions within 192 to 240 h of U exposure. A consolidated investigation using kinetics, microscopy, and physiological and biochemical analyses suggested a role of inducible alkaline phosphatase activity of cell aggregates/akinetes in facilitating the germination of akinetes leading to substantial regeneration of A. torulosa by 384 h of uranyl incubation. The biomineralized uranium appeared to be stable following cell regeneration. Altogether, our results reveal novel insights into the survival mechanism adopted by A. torulosa to resist sustained uranium toxicity under phosphate-limited oxic conditions. IMPORTANCE Long-term effects of uranyl exposure in cyanobacteria under oxic phosphate-limited conditions have been inadequately explored. We conducted a comprehensive examination of the metabolic responses displayed by a marine cyanobacterium

  2. Unusual Versatility of the Filamentous, Diazotrophic Cyanobacterium Anabaena torulosa Revealed for Its Survival during Prolonged Uranium Exposure.

    PubMed

    Acharya, Celin; Chandwadkar, Pallavi; Nayak, Chandrani

    2017-05-01

    Reports on interactions between cyanobacteria and uranyl carbonate are rare. Here, we present an interesting succession of the metabolic responses employed by a marine, filamentous, diazotrophic cyanobacterium, Anabaena torulosa for its survival following prolonged exposure to uranyl carbonate extending up to 384 h at pH 7.8 under phosphate-limited conditions. The cells sequestered uranium (U) within polyphosphates on initial exposure to 100 μM uranyl carbonate for 24 to 28 h. Further incubation until 120 h resulted in (i) significant degradation of cellular polyphosphates causing extensive chlorosis and cell lysis, (ii) akinete differentiation followed by (iii) extracellular uranyl precipitation. X-ray diffraction (XRD) analysis, fluorescence spectroscopy, X-ray absorption near edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) spectroscopy established the identity of the bioprecipitated uranium as a U(VI) autunite-type mineral, which settled at the bottom of the vessel. Surprisingly, A. torulosa cells resurfaced as small green flakes typical of actively growing colonies on top of the test solutions within 192 to 240 h of U exposure. A consolidated investigation using kinetics, microscopy, and physiological and biochemical analyses suggested a role of inducible alkaline phosphatase activity of cell aggregates/akinetes in facilitating the germination of akinetes leading to substantial regeneration of A. torulosa by 384 h of uranyl incubation. The biomineralized uranium appeared to be stable following cell regeneration. Altogether, our results reveal novel insights into the survival mechanism adopted by A. torulosa to resist sustained uranium toxicity under phosphate-limited oxic conditions. IMPORTANCE Long-term effects of uranyl exposure in cyanobacteria under oxic phosphate-limited conditions have been inadequately explored. We conducted a comprehensive examination of the metabolic responses displayed by a marine cyanobacterium, Anabaena

  3. Randomized Trial of Prolonged Exposure for Posttraumatic Stress Disorder with and without Cognitive Restructuring: Outcome at Academic and Community Clinics

    ERIC Educational Resources Information Center

    Foa, Edna B.; Hembree, Elizabeth A.; Cahill, Shawn P.; Rauch, Sheila A. M.; Riggs, David S.; Feeny, Norah C.; Yadin, Elna

    2005-01-01

    Female assault survivors (N = 171) with chronic posttraumatic stress disorder (PTSD) were randomly assigned to prolonged exposure (PE) alone, PE plus cognitive restructuring (PE/CR), or wait-list (WL). Treatment, which consisted of 9-12 sessions, was conducted at an academic treatment center or at a community clinic for rape survivors. Evaluations…

  4. Effects of processing and prolonged high temperature exposure on the microstructure of Nb-1Zr-C sheet

    NASA Technical Reports Server (NTRS)

    Uz, Mehmet; Titran, R. H.

    1993-01-01

    High temperature stability of the microstructure of Nb-1Zr sheet containing 0.1 and 0.06 wt. percent C was studied as affected by processing and prolonged 1350 K exposure with and without applied stress. Sheets were fabricated by cold rolling bars that were single-, double-, or triple-extruded at 1900 K. Creep samples were double-annealed (1 h at 1755 K + 2 h at 1475 K) prior to testing at 1350 K and 10,000 - 34,500 h. The microstructures of the as-cast, extruded, rolled, DA, and crept samples were characterized using various metallographic and analytical methods. The precipitates were rather coarse Nb2C initially, but transformed to finer (less than or equal to 1 micron) carbides of (Zr, Nb)C with each subsequent high temperature process. The grain size, and the relative amount and morphology of (Zr, Nb)C were found to be affected by the number of extrusions and to some extent by C-content. However, the microstructures of all the crept samples were similar with (Zr, Nb)C distributed throughout the matrix indicating that prolonged exposure to 1350 K gave rise to complete transformation of Nb2C to (Zr, Nb)C regardless of the processing history. These and other observations are presented with the emphasis on the correlation between processing, microstructure, and creep properties.

  5. Prolonged Exposure Therapy for Combat-Related Posttraumatic Stress Disorder: Comparing Outcomes for Veterans of Different Wars

    PubMed Central

    Yoder, Matthew; Tuerk, Peter W.; Price, Matthew; Grubaugh, Anouk L.; Strachan, Martha; Myrick, Hugh; Acierno, Ron

    2012-01-01

    There is significant support for exposure therapy as an effective treatment for posttraumatic stress disorder (PTSD) across a variety of populations, including veterans; however, there is little empirical information regarding how veterans of different war theaters respond to exposure therapy. Accordingly, questions remain regarding therapy effectiveness for treatment of PTSD for veterans of different eras. Such questions have important implications for the dissemination of evidence based treatments, treatment development, and policy. The current study compared treatment outcomes across 112 veterans of the Vietnam War, the first Persian Gulf War, and the wars in Afghanistan and Iraq. All subjects were diagnosed with PTSD and enrolled in Prolonged Exposure (PE) treatment. Veterans from all three groups showed significant improvement in PTSD symptoms, with veterans from Vietnam and Afghanistan/Iraq responding similarly to treatment. Persian Gulf veterans did not respond to treatment at the same rate or to the same degree as veterans from the other two eras. Questions and issues regarding the effectiveness of evidence based treatment for veterans from different eras are discussed. PMID:22449084

  6. Prolonged exposure therapy for combat-related posttraumatic stress disorder: comparing outcomes for veterans of different wars.

    PubMed

    Yoder, Matthew; Tuerk, Peter W; Price, Matthew; Grubaugh, Anouk L; Strachan, Martha; Myrick, Hugh; Acierno, Ron

    2012-02-01

    There is significant support for exposure therapy as an effective treatment for posttraumatic stress disorder (PTSD) across a variety of populations, including veterans; however, there is little empirical information regarding how veterans of different war theaters respond to exposure therapy. Accordingly, questions remain regarding therapy effectiveness for treatment of PTSD for veterans of different eras. Such questions have important implications for the dissemination of evidence based treatments, treatment development, and policy. The current study compared treatment outcomes across 112 veterans of the Vietnam War, the first Persian Gulf War, and the wars in Afghanistan and Iraq. All subjects were diagnosed with PTSD and enrolled in prolonged exposure (PE) treatment. Veterans from all three groups showed significant improvement in PTSD symptoms, with veterans from Vietnam and Afghanistan/Iraq responding similarly to treatment. Persian Gulf veterans did not respond to treatment at the same rate or to the same degree as veterans from the other two eras. Questions and issues regarding the effectiveness of evidence based treatment for veterans from different eras are discussed.

  7. Reprocessing WFC3/IR Exposures Affected by Time-Variable Backgrounds

    NASA Astrophysics Data System (ADS)

    Brammer, G.

    2016-11-01

    The background seen in WFC3/IR observations frequently shows strong time-dependent behavior above the constant flux expected for zodiacal continuum light. This is often caused by an emission line of helium at 1.083 μm excited in the sun-illuminated upper atmosphere, when seen in the filters (F105W, F110W) and grisms (G102, G141) sensitive to the feature. The default behavior of the calwf3 pipeline assumes constant source-plus-background fluxes when it performs up-the-ramp fitting to identify cosmic rays and determine the average count rate within a MULTIACCUM IR exposure. calwf3 provides undesirable results in the presence of strongly variable backgrounds, primarily in the form of elevated and non-Gaussian noise in the FLT products. Here we describe methods to improve the noise properties of the reduced products. In the first, we simply turn off the calwf3 crcorr step, treating the IR detector as if it were a CCD, i.e., accumulating flux and reading it out at the end of the exposure. Next, we artificially flatten the ramps in the IMA products and then allow calwf3 to proceed as normal fitting the ramp and identifying CRs. Either of these procedures enable recovery of datasets otherwise corrupted beyond repair and have no discernible effects on photometry of sources in deep combined images.

  8. Prolonged exposure to arsenic in UK private water supplies: toenail, hair and drinking water concentrations.

    PubMed

    Middleton, D R S; Watts, M J; Hamilton, E M; Fletcher, T; Leonardi, G S; Close, R M; Exley, K S; Crabbe, H; Polya, D A

    2016-05-18

    Chronic exposure to arsenic (As) in drinking water is an established cause of cancer and other adverse health effects. Arsenic concentrations >10 μg L(-1) were previously measured in 5% of private water supplies (PWS) in Cornwall, UK. The present study investigated prolongued exposure to As by measuring biomarkers in hair and toenail samples from 212 volunteers and repeated measurements of As in drinking water from 127 households served by PWS. Strong positive Pearson correlations (rp = 0.95) indicated stability of water As concentrations over the time period investigated (up to 31 months). Drinking water As concentrations were positively correlated with toenail (rp = 0.53) and hair (rp = 0.38) As concentrations - indicative of prolonged exposure. Analysis of washing procedure solutions provided strong evidence of the effective removal of exogenous As from toenail samples. Significantly higher As concentrations were measured in hair samples from males and smokers and As concentrations in toenails were negatively associated with age. A positive association between seafood consumption and toenail As and a negative association between home-grown vegetable consumption and hair As was observed for volunteers exposed to <1 As μg L(-1) in drinking water. These findings have important implications regarding the interpretation of toenail and hair biomarkers. Substantial variation in biomarker As concentrations remained unaccounted for, with soil and dust exposure as possible explanations.

  9. Factors related to clinician attitudes toward prolonged exposure therapy for PTSD.

    PubMed

    Ruzek, Josef I; Eftekhari, Afsoon; Rosen, Craig S; Crowley, Jill J; Kuhn, Eric; Foa, Edna B; Hembree, Elizabeth A; Karlin, Bradley E

    2014-08-01

    This study examines pretraining attitudes toward prolonged exposure (PE) therapy in a sample of 1,275 mental health clinicians enrolled in a national PE training program sponsored by the U.S. Department of Veterans Affairs. Attitudes assessed via survey included values placed on outcomes targeted by PE, outcome expectancies (positive expectancies for patient improvement and negative expectancies related to patient deterioration, clinician time burden, and clinician emotional burden), and self-efficacy for delivering PE. Results indicated that clinicians were receptive to learning PE and had positive expectations about the treatment, but expressed concerns that PE might increase patient distress. Responses varied by clinician characteristics with psychologists, clinicians working in specialty PTSD treatment settings (as opposed to those in mental health clinics and other clinic types), and those with a primarily cognitive-behavioral orientation expressing attitudes that were most supportive of learning and implementing PE across various indicators. Implications for addressing attitudinal barriers to implementation of PE therapy are discussed. Published 2014. This article is a US Government work and is in the public domain in the USA.

  10. Outcomes of Prolonged Exposure therapy for veterans with posttraumatic stress disorder.

    PubMed

    Goodson, Jason T; Lefkowitz, Carin M; Helstrom, Amy W; Gawrysiak, Michael J

    2013-08-01

    Prolonged Exposure (PE) is an evidenced-based psychotherapy for posttraumatic stress disorder (PTSD) that is being disseminated nationally within the U.S. Department of Veterans Affairs (VA) with promising initial results. Empirical evidence, however, regarding the effectiveness of PE for treatment of PTSD in military veterans is limited. Building on previous treatment outcome research, the current study investigated the effectiveness of PE in a diverse veteran sample. One-hundred fifteen veterans were enrolled in PE at an urban VA medical center and its surrounding outpatient clinics. PTSD and depression symptoms as well as quality of life were measured before and after treatment. Several baseline patient characteristics were examined as predictors of treatment response. Eighty-four participants completed treatment. Participants experienced a 42% reduction in PTSD symptoms, a 31% reduction in depression symptoms, and an increase in quality of life following PE. Veterans not prescribed psychotropic medication reported greater PTSD symptom reduction than veterans prescribed such medication. The implications of these results for treatment programs targeting PTSD in veterans are discussed. Copyright © 2013 International Society for Traumatic Stress Studies.

  11. The Relationship between Posttraumatic and Depressive Symptoms during Prolonged Exposure with and without Cognitive Restructuring for the Treatment of Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Aderka, Idan M.; Gillihan, Seth J.; McLean, Carmen P.; Foa, Edna B.

    2013-01-01

    Objective: In the present study, we examined the relationship between posttraumatic and depressive symptoms during prolonged exposure (PE) treatment with and without cognitive restructuring (CR) for the treatment of posttraumatic stress disorder (PTSD). Method: Female assault survivors (N = 153) with PTSD were randomized to either PE alone or PE…

  12. Prolonged exposure does not increase soil microbial community compositional response to warming along geothermal gradients.

    PubMed

    Radujkovic, Dajana; Verbruggen, Erik; Sigurdsson, Bjarni D; Leblans, Niki I W; Janssens, Ivan A; Vicca, Sara; Weedon, James T

    2018-02-01

    Global change is expected to affect soil microbial communities through their responsiveness to temperature. It has been proposed that prolonged exposure to elevated temperatures may lead to progressively larger effects on soil microbial community composition. However, due to the relatively short-term nature of most warming experiments, this idea has been challenging to evaluate. The present study took the advantage of natural geothermal gradients (from +1°C to +19°C above ambient) in two subarctic grasslands to test the hypothesis that long-term exposure (>50 years) intensifies the effect of warming on microbial community composition compared to short-term exposure (5-7 years). Community profiles from amplicon sequencing of bacterial and fungal rRNA genes did not support this hypothesis: significant changes relative to ambient were observed only starting from the warming intensity of +9°C in the long term and +7°C/+3°C in the short term, for bacteria and fungi, respectively. Our results suggest that microbial communities in high-latitude grasslands will not undergo lasting shifts in community composition under the warming predicted for the coming 100 years (+2.2°C to +8.3°C). © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Dynamics of immediate early gene and neuropeptide gene response to prolonged immobilization stress: evidence against a critical role of the termination of exposure to the stressor.

    PubMed

    Trnecková, Lenka; Rotllant, David; Klenerová, Vera; Hynie, Sixtus; Armario, Antonio

    2007-02-01

    Stress-induced expression of immediate early genes (IEGs) appears to be transient even if the exposure to the stressor persists. However, there are some exceptions which suggest that particular characteristics of stressors can affect the dynamics of IEG expression. We studied in selected telencephalic, diencephalic and brainstem regions the mRNA levels of two clearly distinct IEGs (c-fos and arc) during prolonged exposure to a severe stressor such as immobilization (IMO) and after releasing the rats from the situation. Although regional differences were observed with the two IEGs, overall, c-fos mRNA levels progressively declined over the course of 4 h of continuous exposure to IMO, whereas arc mRNA levels were maintained at high levels in the brain regions that express this gene under stress (telencephalon). Levels of CRF hnRNA in the hypothalamus paraventricular nucleus only slightly declined during prolonged exposure to IMO. Surprisingly, termination of exposure to IMO did not modify CRF gene expression in the paraventricular nucleus or the pattern of IEGs expression, with the exception of c-fos in the lateral septum. Thus, putative signals associated to the termination of exposure to IMO were unable to modify either IEG expression in most brain areas or CRF gene expression in the paraventricular nucleus.

  14. Ultraviolet light sensitivity and prolonged UVR-erythema

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilson, P.D.; Kaidbey, K.H.; Kligman, A.M.

    The erythema and tanning responses in skin type I (n . 15) and skin type IV (n . 17) have been compared in caucasoids following a single exposure to solar simulated radiation. The former sunburn easily and do not tan while the latter do not burn and tan readily. The dose of radiation was 5 times the Minimal Erythema Dose (MED). The test sites were the extensor aspect of the forearm (exposed site) and flexor aspect of the upper arm (nonexposed site). The responses were monitored at 24 and 48 hr and then twice weekly for 8 weeks. The groupmore » of skin type I individuals had a lower MED and a much more prolonged erythema on both the exposed and nonexposed sites than the group of type IV individuals. All differences were highly significant (p less than 0.005). After 4 weeks erythema remained present in all of the type I subjects but had disappeared in 16 of the 17 type IV subjects. Within the groups there was no difference between erythema duration on exposed vs. nonexposed sites, but there was a highly significant difference (p less than 0.005) between the lower MED on the upper arm and higher MED on the forearm. These results contrast with those of other reports in which prolonged erythema could not be correlated with fair complexion, sunburn sensitivity, ethnic background, or skin type but was instead found to be a distinct feature of persons who had developed nonmelanoma skin cancer. Since prolonged erythema is related to skin type it is therefore not solely a feature of patients with skin cancer.« less

  15. Changes in CR-39 proton sensitivity due to prolonged exposure to high vacuums relevant to the National Ignition Facility and OMEGA.

    PubMed

    Manuel, M J-E; Rosenberg, M J; Sinenian, N; Rinderknecht, H; Zylstra, A B; Séguin, F H; Frenje, J; Li, C K; Petrasso, R D

    2011-09-01

    When used at facilities like OMEGA and the NIF, CR-39 is exposed to high vacuum environments before and after irradiation by charged particles and neutrons. Using an electrostatic linear accelerator at MIT, studies have been conducted to investigate the effects of high vacuum exposure on the sensitivity of CR-39 to fusion protons in the ~1-9 MeV energy range. High vacuum conditions, of order 10(-5) Torr, experienced by CR-39 samples at these facilities were emulated. It is shown that vacuum exposure times longer than ~16 h before proton irradiation result in a decrease in proton sensitivity, whereas no effect was observed for up to 67 h of vacuum exposure after proton irradiation. CR-39 sensitivity curves are presented for samples with prolonged exposure to high vacuum before and after proton irradiation. © 2011 American Institute of Physics

  16. Signal transduction disturbance related to hepatocarcinogenesis in mouse by prolonged exposure to Nanjing drinking water.

    PubMed

    Zhang, Rui; Sun, Jie; Zhang, Yan; Cheng, Shupei; Zhang, Xiaowei

    2013-09-01

    Toxicogenomic approaches were used to investigate the potential hepatocarcinogenic effects on mice by oral exposure to Nanjing drinking water (NJDW). Changes in the hepatic transcriptome of 3 weeks male mice (Mus musculus) were monitored and dissected after oral exposure to NJDW for 90 days. No preneoplastic and neoplastic lesions were observed in the hepatic tissue by the end of NJDW exposure. However, total of 746 genes were changed transcriptionally. Thirty-one percent of differentially expressed genes (DEGs) were associated with the functional categories of cell cycle regulation, adhesion, growth, apoptosis, and signal transduction, which are closely implicated in tumorigenesis and progression. Interrogation of Kyoto Encyclopedia of Genes and Genomes revealed that 43 DEGs were mapped to several crucial signaling pathways implicated in the pathogenesis of hepatocellular carcinoma (HCC). In signal transduction network constructed via Genes2Networks software, Egfr, Akt1, Atf2, Ctnnb1, Hras, Mapk1, Smad2, and Ccnd1 were hubs. Direct gene-disease relationships obtained from Comparative Toxicogenomics Database and scientific literatures revealed that the hubs have direct mechanism or biomarker relationships with hepatocellular preneoplastic lesions or hepatocarcinogenesis. Therefore, prolonged intake of NJDW without employing any indoor water treatment strategy might predispose mouse to HCC. Furthermore, Egfr, Akt1, Ctnnb1, Hras, Mapk1, Smad2, and Ccnd1 were identified as promising biomarkers of the potential combined hepatocarcinogenicity.

  17. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia

    PubMed Central

    Hansen, Jim; Sander, Mikael

    2003-01-01

    Acute exposure to hypoxia causes chemoreflex activation of the sympathetic nervous system. During acclimatization to high altitude hypoxia, arterial oxygen content recovers, but it is unknown to what degree sympathetic activation is maintained or normalized during prolonged exposure to hypoxia. We therefore measured sympathetic nerve activity directly by peroneal microneurography in eight healthy volunteers (24 ± 2 years of age) after 4 weeks at an altitude of 5260 m (Chacaltaya, Bolivian Andes) and at sea level (Copenhagen). The subjects acclimatized well to altitude, but in every subject sympathetic nerve activity was highly elevated at altitude vs. sea level (48 ± 5 vs. 16 ± 3 bursts min−1, respectively, P < 0.05), coinciding with increased mean arterial blood pressure (87 ± 3 vs. 77 ± 2 mmHg, respectively, P < 0.05). To examine the underlying mechanisms, we administered oxygen (to eliminate chemoreflex activation) and saline (to reduce cardiopulmonary baroreflex deactivation). These interventions had minor effects on sympathetic activity (48 ± 5 vs. 38 ± 4 bursts min−1, control vs. oxygen + saline, respectively, P < 0.05). Moreover, sympathetic activity was still markedly elevated (37 ± 5 bursts min−1) when subjects were re-studied under normobaric, normoxic and hypervolaemic conditions 3 days after return to sea level. In conclusion, acclimatization to high altitude hypoxia is accompanied by a striking and long-lasting sympathetic overactivity. Surprisingly, chemoreflex activation by hypoxia and baroreflex deactivation by dehydration together could account for only a small part of this response, leaving the major underlying mechanisms unexplained. PMID:12563015

  18. Effects of prolonged exposure and virtual reality exposure on suicidal ideation in active duty soldiers: An examination of potential mechanisms.

    PubMed

    Norr, Aaron M; Smolenski, Derek J; Reger, Greg M

    2018-05-12

    The current study sought to investigate the effects of exposure therapy on suicidal ideation (SI), as well as potential mechanistic pathways of SI reduction among active duty military personnel. Active duty army soldiers (N = 162) were recruited from a military base in the U.S. and were enrolled in a randomized clinical trial comparing Prolonged Exposure (PE), Virtual Reality Exposure (VRE), and a wait-list control for the treatment of posttraumatic stress disorder (PTSD) stemming from deployments to Iraq or Afghanistan. PTSD diagnosis followed DSM-IV-TR criteria. Outcome measures were assessed via self-report and clinician interview. PTSD symptoms, depressive symptoms, and SI were included in an autoregressive cross-lagged panel model to examine mechanistic pathways. Analyses revealed that PE/VRE had a lower probability of post-treatment suicidal ideation (OR = 0.23, 95% CI [0.06, 0.86]) compared to the waitlist control. Mediation analyses revealed a significant indirect effect from treatment condition to post-treatment PTSD symptoms through mid-treatment SI (Estimate = -1.420, 95% CI -3.559, -0.223]). Baseline suicidal ideation did not interact with treatment condition to predict PTSD symptom change at mid-treatment (p = .231) or post-treatment (p = .672). PE/VRE successfully reduced SI, and the presence of SI at baseline did not affect PTSD symptom reduction, promoting the utility of using PE/VRE to address suicidality among individuals with PTSD. Mediation analyses suggest that reductions in SI were achieved early in treatment. Published by Elsevier Ltd.

  19. Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats.

    PubMed

    Lai, Shuhua; Wu, Gangwei; Jiang, Zhixian

    2018-01-01

    Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli. © 2018 The Author(s). Published by S. Karger AG, Basel.

  20. Intraocular pressure and cerebral oxygenation during prolonged headward acceleration.

    PubMed

    Eiken, Ola; Keramidas, Michail E; Taylor, Nigel A S; Grönkvist, Mikael

    2017-01-01

    Supra-tolerance head-to-foot directed gravitoinertial load (+Gz) typically induces a sequence of symptoms/signs, including loss of: peripheral vision-central vision-consciousness. The risk of unconsciousness is greater when anti-G-garment failure occurs after prolonged rather than brief exposures, presumably because, in the former condition, mental signs are not consistently preceded by impaired vision. The aims were to investigate if prolonged exposure to moderately elevated +Gz reduces intraocular pressure (IOP; i.e., improves provisions for retinal perfusion), or the cerebral anoxia reserve. Subjects were exposed to 4-min +Gz plateaux either at 2 and 3 G (n = 10), or at 4 and 5 G (n = 12). Measurements included eye-level mean arterial pressure (MAP), oxygenation of the cerebral frontal cortex, and at 2 and 3 G, IOP. IOP was similar at 1 (14.1 ± 1.6 mmHg), 2 (14.0 ± 1.6 mmHg), and 3 G (14.0 ± 1.6 mmHg). During the G exposures, MAP exhibited an initial prompt drop followed by a partial recovery, end-exposure values being reduced by ≤30 mmHg. Cerebral oxygenation showed a similar initial drop, but without recovery, and was followed by either a plateau or a further slight decrement to a minimum of about -14 μM. Gz loading did not affect IOP. That cerebral oxygenation remained suppressed throughout these G exposures, despite a concomitant partial recovery of MAP, suggests that the increased risk of unconsciousness upon G-garment failure after prolonged +Gz exposure is due to reduced cerebral anoxia reserve.

  1. Treating Low-Income and Minority Women with Posttraumatic Stress Disorder: A Pilot Study Comparing Prolonged Exposure and Treatment as Usual Conducted by Community Therapists

    ERIC Educational Resources Information Center

    Feske, Ulrike

    2008-01-01

    Twenty-one female psychiatric outpatients with chronic posttraumatic stress disorder (PTSD) are randomly assigned to prolonged exposure (PE; n = 9) for PTSD or treatment as usual (TAU; n = 12). Participants are predominately low income and African American with complex trauma and psychiatric histories. Treatment is delivered by community…

  2. Effects of five sulphonamides on duckweed (Lemna minor) after prolonged exposure time and their dependency on photoradiation.

    PubMed

    Białk-Bielińska, Anna; Matzke, Marianne; Caban, Magda; Stolte, Stefan; Kumirska, Jolanta; Stepnowski, Piotr

    2018-03-15

    Sulphonamides (SAs) are one of the most commonly used veterinary drugs and therefore their residues are regularly found in the environment. So far scientific attention has mostly been paid to the evaluation of their acute ecotoxicological effects with data on long-term effects for non-target organisms still largely missing. Therefore, the main aim of this study was to evaluate the potential toxicities of five sulphonamides to duckweed (Lemna minor) after prolonged exposure time (14days). To elucidate whether their phytotoxic effects result from potential photodegradation products, the toxicity of standard solutions of selected sulphonamides was also investigated in a standard 7-day test but after irradiation (by keeping them under the test conditions) for the selected time (after 7 and 14days). The ecotoxicological tests were accompanied by chemical analyses to be able to link the observed effects to the concentrations and nature of the exposed compounds. The results showed a shift in the toxicity of SAs: a strong decrease in toxicity for the two most toxic sulphonamides (sulphamethoxazole and sulphadimethoxine) and a slight increase in toxicity for three other SAs (sulphadimidine, sulphathiazole, sulphamerazine) in the prolonged test. However, a decrease in the toxicity and concentration of all the SAs was observed when stock solutions were irradiated prior to the toxicity experiment, which suggests that the observed effects towards L. minor of five SAs in the prolonged test cannot be directly associated with the degradation of these compounds under the test conditions but with their different mode of toxic action towards these organisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Coexistence of Ureaplasma and chorioamnionitis is associated with prolonged mechanical ventilation.

    PubMed

    Jung, Euiseok; Choi, Chang Won; Kim, Su Yeong; Sung, Tae-Jung; Kim, Haeryoung; Park, Kyoung Un; Kim, Han-Suk; Kim, Beyong Il; Choi, Jung-Hwan

    2017-01-01

    Both histologic chorioamnionitis (HCAM) and Ureaplasma infection are considered important contributors to perinatal lung injury. We tested the hypothesis that coexistence of maternal HCAM and perinatal Ureaplasma exposure increases the risk of prolonged mechanical ventilation in extremely low-birthweight (ELBW) infants. A retrospective cohort study was carried out of all ELBW infants born between January 2008 and December 2013 at a single academic center. Placental pathology and gastric fluid Ureaplasma data were available for all infants. Culture and polymerase chain reaction were used to detect Ureaplasma in gastric fluid. Prolonged mechanical ventilation was defined as mechanical ventilation that began within 28 days after birth and continued. Of 111 ELBW infants enrolled, 84 survived beyond 36 weeks of postmenstrual age (PMA) and were included in the analysis. Eighteen infants (21.4%) had both HCAM and Ureaplasma exposure. Seven infants (8.3%) required mechanical ventilation beyond 36 weeks of PMA. Coexistence of HCAM and Ureaplasma in gastric fluid was significantly associated with prolonged mechanical ventilation after adjustment for gestational age, sex, mode of delivery, and use of macrolide antibiotics (OR, 8.7; 95%CI: 1.1-67.2). Coexistence of maternal HCAM and perinatal Ureaplasma exposure significantly increases the risk of prolonged mechanical ventilation in ELBW infants. © 2016 Japan Pediatric Society.

  4. Educational background: different processes and consequences on health and physical and mental exposures among women and men.

    PubMed

    Dahlberg, Raymond; Bildt, Carina; Vingård, Eva; Karlqvist, Lena

    2007-01-01

    To compare health and exposures at work and at home of women and men with the same educational background. The study group consisted of 3831 individuals, grouped into three educational categories based on length of education. Category 1, which represents 9-year compulsory school; Category 2, which includes 3-year upper secondary school, i.e. in total 12 years of education; and Category 3, which includes post-secondary school, such as university. They responded to a questionnaire that included questions on health and exposures at work and at home. Significant differences were shown in health outcomes between women and men with the same educational background and also in exposures in their professional and private lives. Associations between educational background and health were found and analyses revealed that men with a university education run the lowest risk of developing ill health. Women with the same educational background as men are differently exposed, both in paid and unpaid work, due to the segregated labour market and the unequal distribution of domestic duties. Men in all educational categories studied had better health compared to women with the same educational background.

  5. Homework "Dose," Type, and Helpfulness as Predictors of Clinical Outcomes in Prolonged Exposure for PTSD.

    PubMed

    Cooper, Andrew A; Kline, Alexander C; Graham, Belinda; Bedard-Gilligan, Michele; Mello, Patricia G; Feeny, Norah C; Zoellner, Lori A

    2017-03-01

    Homework is often viewed as central to prolonged exposure (PE) for posttraumatic stress disorder (PTSD), but its relationship with treatment outcome is not well understood. We evaluated homework type, dose, and patients' perceptions of helpfulness as predictors of symptom change and posttreatment outcomes in PE. Patients with chronic PTSD received PE in a randomized clinical trial. Independent evaluators assessed PTSD severity at pre- and posttreatment. Patients reported homework adherence and perceived helpfulness at the beginning of each session, separately for in vivo and imaginal exposure assignments. These variables were examined as predictors of change in PTSD symptoms, PTSD remission, and good end-state functioning (GESF; low PTSD, depression, and anxiety) at posttreatment. Higher imaginal homework adherence predicted greater symptom improvement between sessions and across treatment, as well as twice the odds of achieving remission and GESF. Patients who were at least moderately adherent to imaginal homework assignments (two or more times a week) reported more symptom gains than those who were least adherent but did not differ from those who were most adherent. In vivo adherence was not consistently associated with better outcome, perhaps due to heterogeneity in form and function of weekly assignments. Higher ratings of helpfulness of both types of homework predicted greater symptom improvement from pre- to posttreatment and between sessions. Overall, imaginal exposure homework may complement in-session exposures by enhancing key change processes, though perfect adherence is not necessary. Patients' perceptions of helpfulness may reflect buy-in or perceived match between homework completion and functional impairment. Clinically, in addition to targeting adherence to homework assignments, querying about perceived helpfulness and adjusting assignments appropriately may help augment clinical gains. Copyright © 2016. Published by Elsevier Ltd.

  6. Prolonged restraint stressor exposure in outbred CD-1 mice impacts microbiota, colonic inflammation, and short chain fatty acids.

    PubMed

    Maltz, Ross M; Keirsey, Jeremy; Kim, Sandra C; Mackos, Amy R; Gharaibeh, Raad Z; Moore, Cathy C; Xu, Jinyu; Bakthavatchalu, Vasudevan; Somogyi, Arpad; Bailey, Michael T

    2018-01-01

    Stressor-exposure has been shown to exacerbate inflammation and change the composition of the gastrointestinal microbiota; however stressor-induced effects on microbiota-derived metabolites and their receptors are unknown. Thus, bacterial-produced short chain fatty acids (SCFAs), as well as microbial community composition, were assessed in the colons of mice exposed to stress during infection with Citrobacter rodentium. Mice were exposed to overnight restraint on 7 consecutive nights, or left undisturbed as a control. After the first exposure of restraint, mice were orally challenged with C. rodentium or with vehicle. Microbial community composition was assessed using 16S rRNA gene sequencing and SCFA levels measured using gas chromatography-mass spectrometry (GC-MS). Pathogen levels and colonic inflammation were also assessed 6 days post-infection. Results demonstrated that the microbial community structure and SCFA production were significantly affected by both stressor exposure and C. rodentium-infection. Exposure to prolonged restraint in the absence of infection significantly reduced SCFAs (acetic acid, butyric acid, and propionic acid). Multiple bacterial taxa were affected by stressor exposure, with the relative abundance of Lactobacillus being significantly reduced and directly correlated with propionic acid. Lactobacillus abundances were inversely correlated with colonic inflammation, supporting the contention that Lactobacillus helps to regulate mucosal inflammatory responses. Our data indicates that restraint stressor can have significant effects on pathogen-induced colonic inflammation and suggest that stressor-induced changes in the microbiota, microbial-produced SCFAs and their receptors may be involved.

  7. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; van Rhoon, G. C.; Verduijn, G. M.; Naus-Postema, N. C.; Paulides, M. M.

    2016-01-01

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg-1) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients’ feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R 2  =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature

  8. Prolonged exposure of mixed aerobic cultures to low temperature and benzalkonium chloride affect the rate and extent of nitrification.

    PubMed

    Yang, Jeongwoo; Tezel, Ulas; Li, Kexun; Pavlostathis, Spyros G

    2015-03-01

    The combined effect of benzalkonium chloride (BAC) and prolonged exposure to low temperature on nitrification was investigated. Ammonia oxidation at 22-24°C by an enriched nitrifying culture was inhibited at increasing BAC concentrations and ceased at 15 mg BAC/L. The non-competitive inhibition coefficient was 1.5±0.9 mg BAC/L. Nitrification tests were conducted without and with BAC at 5mg/L using an aerobic, mixed heterotrophic/nitrifying culture maintained at a temperature range of 24-10°C. Maintaining this culture at 10°C for over one month in the absence of BAC, resulted in slower nitrification kinetics compared to those measured when the culture was first exposed to 10°C. BAC was degraded by the heterotrophic population, but its degradation rate decreased significantly as the culture temperature decreased to 10°C. These results confirm the negative impact of quaternary ammonium compounds on the nitrification process, which is further exacerbated by prolonged, low temperature conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Improved space object detection using short-exposure image data with daylight background.

    PubMed

    Becker, David; Cain, Stephen

    2018-05-10

    Space object detection is of great importance in the highly dependent yet competitive and congested space domain. The detection algorithms employed play a crucial role in fulfilling the detection component in the space situational awareness mission to detect, track, characterize, and catalog unknown space objects. Many current space detection algorithms use a matched filter or a spatial correlator on long-exposure data to make a detection decision at a single pixel point of a spatial image based on the assumption that the data follow a Gaussian distribution. Long-exposure imaging is critical to detection performance in these algorithms; however, for imaging under daylight conditions, it becomes necessary to create a long-exposure image as the sum of many short-exposure images. This paper explores the potential for increasing detection capabilities for small and dim space objects in a stack of short-exposure images dominated by a bright background. The algorithm proposed in this paper improves the traditional stack and average method of forming a long-exposure image by selectively removing short-exposure frames of data that do not positively contribute to the overall signal-to-noise ratio of the averaged image. The performance of the algorithm is compared to a traditional matched filter detector using data generated in MATLAB as well as laboratory-collected data. The results are illustrated on a receiver operating characteristic curve to highlight the increased probability of detection associated with the proposed algorithm.

  10. Evaluation of Background Exposures of Americans to Dioxin-Like Compounds in the 1990's and the 2000's

    USDA-ARS?s Scientific Manuscript database

    The US Environmental Protection Agency’s 2004 Dioxin Reassessment included a characterization of background exposures to dioxin-like compounds, including an estimate of an average background intake dose and an average background body burden. These quantities were derived from data generated in the m...

  11. Osborn waves in severe accidental hypothermia secondary to prolonged immobilization and malnutrition.

    PubMed

    Rotondi, Francesco; Manganelli, Fiore; Candelmo, Fiore; Marino, Luciano; Di Lorenzo, Emilio; Alfano, Ferdinando; Stanco, Giovanni; Rosato, Giuseppe

    2010-07-01

    We report the case of a 77-year-old man, in whom accidental hypothermia was secondary to prolonged immobilization and malnutrition. The electrocardiogram showed typical Osborn waves, which disappeared with the rewarming of the patient. The diagnosis of hypothermia is easy in patients with a history of prolonged exposure to a cold environment but accidental hypothermia may also occur as a consequence of prolonged immobilization and malnutrition. ECG analysis is very important for a correct and fast diagnosis.

  12. DETERMINING BACKGROUND EXPOSURE TO PETROLEUM AND COMBUSTION BY-PRODUCTS: COMPARISON OF MID-WESTERN AND MID-ATLANTIC REGIONS

    EPA Science Inventory

    Regional background levels of exposure to fish from petroleum and combustion by-products were determined for the state of Ohio and the mid-Atlantic region. Exposures were measured using bile metabolites that fluoresce at 290/335 nm for naphthalene(NAPH)-type compounds and at 380...

  13. Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990–2009

    PubMed Central

    Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

    2016-01-01

    Background: Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. Methods: AL cases diagnosed over 1990–2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002–2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. Results: AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Conclusions: Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland. Citation: Demoury C, Marquant F, Ielsch G, Goujon S, Debayle C, Faure L, Coste A, Laurent O, Guillevic J, Laurier D, Hémon D, Clavel J

  14. Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.

    PubMed

    Bloch-Shilderman, E; Rabinovitz, I; Egoz, I; Yacov, G; Allon, N; Nili, U

    2018-02-01

    VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure. Characterization of such a threshold is crucial for dealing with unresolved operative dilemmas such as when it is safe enough to resettle a population that has been evacuated from a VX-contaminated area. Rats, continuously exposed to various doses of VX (0.225-45 µg/kg/day) for 4 weeks via implanted mini-osmotic pumps, showed a dose-dependent and continuous decrease in ChE activity in whole blood, brain and muscles, ranging between 20 and 100%. Exposure to 13.5 µg/kg/day led to a stable low ChE activity level (~ 20%), accompanied by transient and negligible electrocorticogram spectral power transformations, especially in the theta and alpha brain wave frequencies, and a significant decrease in total brain M2 receptor density. These changes were neither accompanied by observable signs of intoxication nor by changes in motor function, circadian rhythm or TSPO level (a reliable marker of brain damage). Following exposure to lower doses of 2.25 and 0.225 µg/kg/day, the only change measured was a reduction in ChE activity of 60 and 20%, respectively. Based on these results, we delineate ChE inhibition as the physiological measure most susceptible to alterations following prolonged VX exposure, and determine for the first time the threshold sub-acute VX dose for minimal physiological effects (up to 20% reduction in ChE activity) in the rat as 0.225 µg/kg/day.

  15. Competing for Consciousness: Prolonged Mask Exposure Reduces Object Substitution Masking

    ERIC Educational Resources Information Center

    Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

    2011-01-01

    In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask impairs target identification, even though it has different contours from, and does not spatially overlap with the target. Here, we demonstrate a previously unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g., 640 ms) relative to intermediate…

  16. Increased risk of QT prolongation associated with atherosclerotic diseases in arseniasis-endemic area in southwestern coast of Taiwan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, C.-H.; Chen, C.-L.; Hsiao, C.K.

    2009-09-15

    Chronic arsenic exposure has been documented to be associated with various cardiovascular diseases. We aimed to investigate 1) the increased risk of QT prolongation in chronic arsenic exposure, and 2) the relationships of cardiac repolarization (QT interval duration) with ischemic heart disease and carotid atherosclerosis. We studied 280 men and 355 women living in the endemic area of arseniasis in southwestern Taiwan. QT intervals in electrocardiogram and carotid intima-media thickness (IMT) by ultrasonography were measured. Ischemic heart disease was diagnosed by history or abnormal electrocardiogram. Significant associations of the corrected QT interval (QTc) duration with ischemic heart disease and carotidmore » intima-medium thickness and plaque were observed after adjustment for various risk factors in the multiple linear regression analysis (all p values < 0.05). Three indices of chronic arsenic exposure were all significantly associated with the risk of QTc prolongation showing dose-response relationships (p < 0.001). Chronic arsenic exposure was dose-dependently associated with the risk of QTc prolongation. Ischemic heart disease and carotid atherosclerosis were significantly associated with QTc intervals in chronic arsenic exposure. QTc prolongation might be suggested as an early biomarker for ischemic heart disease or carotid atherosclerosis in population with previous exposure to arsenic.« less

  17. Calcium, magnesium, and phosphorus metabolism, and parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on submarines.

    PubMed

    Messier, A A; Heyder, E; Braithwaite, W R; McCluggage, C; Peck, A; Schaefer, K E

    1979-01-01

    Studies of calcium and phosphorus metabolism and acid-base balance were carried out on three Fleet Ballistic Missile (FBM) submarines during prolonged exposure to elevated concentrations of CO2. The average CO2 concentration in the submarine atmosphere during patrols ranged from 0.85% to 1% CO2. In the three studies, in which 9--15 subjects participated, the urinary excretion of calcium and phosphate fell during the first three weeks to a level commensurate with a decrease in plasma calcium and increase in phosphorus. In the fourth week of one patrol, a marked increase was found in urinary calcium excretion, associated with a rise in blood PCO2 and bicarbonate. Urinary calcium excretion decreased again during the 5th to 8th week, with a secondary decrease in blood pH and plasma calcium. During the third patrol, the time course of acid-base changes corresponded well with that found during the second patrol. There was a trend toward an increase in plasma calcium between the fourth and fifth week commensurate with the transient rise in pH and bicarbonate. Plasma parathyroid and calcitonin hormone activities were measured in two patrols and no significant changes were found. Hydroxyproline excretion decreased in the three-week study and remained unchanged in the second patrol, which lasted 57 days. It is suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism is controlled by the uptake and release of CO2 in the bones. The resulting phases in bone buffering, rather than renal regulation, determine acid-base balance.

  18. Prolonged exposure to WIN55,212-2 causes down-regulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy

    PubMed Central

    Blair, Robert E.; Deshpande, Laxmikant S.; Sombati, Sompong; Elphick, Maurice R.; Martin, Billy R.; DeLorenzo, Robert J.

    2009-01-01

    Summary Cannabinoids have been shown to cause CB1-receptor dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype. This study was carried out to evaluate the effects of prolonged exposure to the CB1 agonist WIN55,212-2 on seizure activity in a hippocampal neuronal culture model of low-Mg2+ induced spontaneous recurrent epileptiform discharges (SREDs). Following low-Mg2+ induced SREDs, cultures were returned to maintenance media containing 10, 100 or 1000 nM WIN55,212-2 from 4 to 24 hours. Whole-cell current-clamp analysis of WIN55,212-2 treated cultures revealed a concentration-dependent increase in SRED frequency. Immunocytochemical staining revealed that WIN55,212-2 treatment induced a concentration-dependent down-regulation of the CB1 receptor in neuronal processes and at both glutamatergic and GABAergic presynaptic terminals. Prolonged exposure to the inactive enantiomer WIN55,212-3 in low-Mg2+ treated cultures had no effect on the frequency of SREDs or CB1 receptor staining. The results from this study further substantiate a role for a tonic CB1 receptor-dependent endocannabinoid regulation of seizure discharge and suggest that prolonged exposure to cannabinoids results in the development of tolerance to the anticonvulsant effects of cannabinoids and an exacerbation of seizure activity in the epileptic phenotype. PMID:19540252

  19. Music exposure induced prolongation of cardiac allograft survival and generated regulatory CD4⁺ cells in mice.

    PubMed

    Uchiyama, M; Jin, X; Zhang, Q; Amano, A; Watanabe, T; Niimi, M

    2012-05-01

    In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. “Estimating Regional Background Air Quality using Space/Time Ordinary Kriging to Support Exposure Studies”

    EPA Science Inventory

    Local-scale dispersion models are increasingly being used to perform exposure assessments. These types of models, while able to characterize local-scale air quality at increasing spatial scale, however, lack the ability to include background concentration in their overall estimat...

  1. Pattern of Change in Prolonged Exposure and Cognitive-Processing Therapy for Female Rape Victims With Posttraumatic Stress Disorder

    PubMed Central

    Nishith, Pallavi; Resick, Patricia A.; Griffin, Michael G.

    2010-01-01

    Curve estimation techniques were used to identify the pattern of therapeutic change in female rape victims with posttraumatic stress disorder (PTSD). Within-session data on the Posttraumatic Stress Disorder Symptom Scale were obtained, in alternate therapy sessions, on 171 women. The final sample of treatment completers included 54 prolonged exposure (PE) and 54 cognitive-processing therapy (CPT) completers. For both PE and CPT, a quadratic function provided the best fit for the total PTSD, reexperiencing, and arousal scores. However, a difference in the line of best fit was observed for the avoidance symptoms. Although a quadratic function still provided a better fit for the PE avoidance, a linear function was more parsimonious in explaining the CPT avoidance variance. Implications of the findings are discussed. PMID:12182271

  2. Prolonged exposure for the treatment of Spanish-speaking Puerto Ricans with posttraumatic stress disorder: a feasibility study

    PubMed Central

    2011-01-01

    Background Most of the empirical studies that support the efficacy of prolonged exposure (PE) for treating posttraumatic stress disorder (PTSD) have been conducted on white mainstream English-speaking populations. Although high PTSD rates have been reported for Puerto Ricans, the appropriateness of PE for this population remains unclear. The purpose of this study was to examine the feasibility of providing PE to Spanish speaking Puerto Ricans with PTSD. Particular attention was also focused on identifying challenges faced by clinicians with limited experience in PE. This information is relevant to help inform practice implications for training Spanish-speaking clinicians in PE. Results Fourteen patients with PTSD were randomly assigned to receive PE (n = 7) or usual care (UC) (n = 7). PE therapy consisted of 15 weekly sessions focused on gradually confronting and emotionally processing distressing trauma-related memories and reminders. Five patients completed PE treatment; all patients attended the 15 sessions available to them. In UC, patients received mental health services available within the health care setting where they were recruited. They also had the option of self-referring to a mental health provider outside the study setting. The Clinician-Administered PTSD Scale (CAPS) was administered at baseline, mid-treatment, and post-treatment to assess PTSD symptom severity. Treatment completers in the PE group demonstrated significantly greater reductions in PTSD symptoms than the UC group. Forty percent of the PE patients showed clinically meaningful reductions in PTSD symptoms from pre- to post-treatment. Conclusions PE appears to be viable for treating Puerto Rican Spanish-speaking patients with PTSD. This therapy had good patient acceptability and led to improvements in PTSD symptoms. Attention to the clinicians' training process contributed strongly to helping them overcome the challenges posed by the intervention and increased their acceptance of PE. PMID

  3. Sleep disturbances as predictors of prolonged exposure therapy effectiveness among veterans with PTSD.

    PubMed

    Sexton, Minden B; Avallone, Kimberly M; Smith, Erin R; Porter, Katherine E; Ashrafioun, Lisham; Todd Arnedt, J; Rauch, Sheila A M

    2017-10-01

    Sleep disturbances (SD) are pronounced in Veterans with posttraumatic stress disorder (PTSD). In clinical trials, SD have been shown to limit the effectiveness of evidence-based treatments for non-PTSD disorders. The purpose of this study was to investigate the relationships between pretreatment SD and the effectiveness of Prolonged Exposure (PE) therapy for Veterans with PTSD. Twenty-one Veterans completed the Pittsburgh Sleep Quality Index (PSQI) and the Clinician Administered PTSD Scale upon presenting to a PTSD specialty clinic. Veterans completed the PTSD Symptom Checklist-Civilian (PCL-C) at the initiation of PE and biweekly thereafter for the duration of treatment (96 total assessments). Correlations and hierarchical linear modeling were utilized to examine the potential impact of baseline sleep variables on the slope and magnitude of treatment outcomes. Higher PSQI total scores, and higher sleep latency and sleep medication use subscale scores were associated with higher PCL-C scores at baseline. Veterans evidenced significant reductions in PTSD symptoms during the course of the treatment study. Total PSQI scores and composites were not associated with reduced effectiveness of PE treatment or the slope of PTSD symptom changes. Sleep disturbances do not preclude Veterans from benefits derived from engagement in this gold standard PTSD intervention. Published by Elsevier B.V.

  4. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: involvement of the adaptive antioxidant response.

    PubMed

    Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E; Pi, Jingbo

    2011-04-08

    There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs³(+)) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs³(+) exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs³(+) exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes. Taken together our studies suggest that prolonged low-level iAs³(+) exposure activates the cellular adaptive oxidative stress response, which impairs insulin-stimulated ROS signaling that is involved in ISGU, and thus causes insulin resistance in adipocytes. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    PubMed Central

    Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E.; Pi, Jingbo

    2011-01-01

    There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs3+) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes. Taken together our studies suggest that prolonged low-level iAs3+ exposure activates the cellular adaptive oxidative stress response, which impairs insulin-stimulated ROS signaling that is involved in ISGU, and thus causes insulin resistance in adipocytes. PMID:21396911

  6. Cultural Adaptations of Prolonged Exposure Therapy for Treatment and Prevention of Posttraumatic Stress Disorder in African Americans

    PubMed Central

    Williams, Monnica T.; Malcoun, Emily; Sawyer, Broderick A.; Davis, Darlene M.; Bahojb Nouri, Leyla; Bruce, Simone Leavell

    2014-01-01

    Posttraumatic stress disorder (PTSD) is a highly disabling disorder, afflicting African Americans at disproportionately higher rates than the general population. When receiving treatment, African Americans may feel differently towards a European American clinician due to cultural mistrust. Furthermore, racism and discrimination experienced before or during the traumatic event may compound posttrauma reactions, impacting the severity of symptoms. Failure to adapt treatment approaches to encompass cultural differences and racism-related traumas may decrease treatment success for African American clients. Cognitive behavioral treatment approaches are highly effective, and Prolonged Exposure (PE) in particular has the most empirical support for the treatment of PTSD. This article discusses culturally-informed adaptations of PE that incorporates race-related trauma themes specific to the Black experience. These include adding more sessions at the front end to better establish rapport, asking directly about race-related themes during the assessment process, and deliberately bringing to the forefront race-related experiences and discrimination during treatment when indicated. Guidelines for assessment and the development of appropriate exposures are provided. Case examples are presented demonstrating adaptation of PE for a survivor of race-related trauma and for a woman who developed internalized racism following a sexual assault. Both individuals experienced improvement in their posttrauma reactions using culturally-informed adaptations to PE. PMID:25379272

  7. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    PubMed

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration. Published by Elsevier B.V.

  8. Defining futile life-prolonging treatments through Neo-Socratic Dialogue

    PubMed Central

    2013-01-01

    Background In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. Methods We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: “What is a life-prolonging treatment?” A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Results Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient’s lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the

  9. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

    PubMed

    Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

    2016-01-01

    Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

  10. Prenatal Nicotinic Exposure Upregulates Pulmonary C-fiber NK1R Expression to Prolong Pulmonary C-fiber-Mediated Apneic Response

    PubMed Central

    Zhao, Lei; Zhuang, Jianguo; Zang, Na; Lin, Yong; Lee, Lu-Yuan; Xu, Fadi

    2015-01-01

    Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA1 receptor, ADA1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA1R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to change BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChRs or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. PMID:26524655

  11. Individual, family background, and contextual explanations of racial and ethnic disparities in youths' exposure to violence.

    PubMed

    Zimmerman, Gregory M; Messner, Steven F

    2013-03-01

    We used data from the Project on Human Development in Chicago Neighborhoods to examine the extent to which individual, family, and contextual factors account for the differential exposure to violence associated with race/ethnicity among youths. Logistic hierarchical item response models on 2344 individuals nested within 80 neighborhoods revealed that the odds of being exposed to violence were 74% and 112% higher for Hispanics and Blacks, respectively, than for Whites. Appreciable portions of the Hispanic-White gap (33%) and the Black-White gap (53%) were accounted for by family background factors, individual differences, and neighborhood factors. The findings imply that programs aimed at addressing the risk factors for exposure to violence and alleviating the effects of exposure to violence may decrease racial/ethnic disparities in exposure to violence and its consequences.

  12. Individual, Family Background, and Contextual Explanations of Racial and Ethnic Disparities in Youths’ Exposure to Violence

    PubMed Central

    Messner, Steven F.

    2013-01-01

    We used data from the Project on Human Development in Chicago Neighborhoods to examine the extent to which individual, family, and contextual factors account for the differential exposure to violence associated with race/ethnicity among youths. Logistic hierarchical item response models on 2344 individuals nested within 80 neighborhoods revealed that the odds of being exposed to violence were 74% and 112% higher for Hispanics and Blacks, respectively, than for Whites. Appreciable portions of the Hispanic–White gap (33%) and the Black–White gap (53%) were accounted for by family background factors, individual differences, and neighborhood factors. The findings imply that programs aimed at addressing the risk factors for exposure to violence and alleviating the effects of exposure to violence may decrease racial/ethnic disparities in exposure to violence and its consequences. PMID:23327266

  13. Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

    PubMed Central

    2014-01-01

    Background Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women’s experiences of prolonged and normal labour. Method Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic and obstetric background, birth outcome and women’s feelings and experiences of birth. The prevalence of prolonged labour, as defined by a documented ICD-code and inspection of partogram was calculated. Four groups were identified; women with prolonged labour as identified by documented ICD-codes or by partogram inspection but no ICD-code; women with normal labour augmented with oxytocin or not. Results Every fifth woman experienced a prolonged labour. The prevalence with the documented ICD-code was (13%) and without ICD-code but positive partogram was (8%). Seven percent of women with prolonged labour were not treated with oxytocin. Approximately one in three women (28%) received oxytocin augmentation despite having no evidence of prolonged labour. The length of labour differed between the four groups of women, from 7 to 23 hours. Women with a prolonged labour had a negative birth experience more often (13%) than did women who had a normal labour (3%) (P <0.00). The factors that contributed most strongly to a negative birth experience in women with prolonged labour were emergency Caesarean section (OR 9.0, 95% CI 1.2-3.0) and to strongly agree with the following statement ‘My birth experience made me decide not to have any more children’ (OR 41.3, 95% CI 4.9-349.6). The factors that contributed most strongly to a negative birth experience in women with normal labour were less agreement with the statement ‘It was exiting to give birth’ (OR 0.13, 95% CI 0

  14. Biomarker monitoring of controlled dietary acrylamide exposure indicates consistent human endogenous background.

    PubMed

    Goempel, Katharina; Tedsen, Laura; Ruenz, Meike; Bakuradze, Tamara; Schipp, Dorothea; Galan, Jens; Eisenbrand, Gerhard; Richling, Elke

    2017-11-01

    The aim of the present study was to explore the relation of controlled dietary acrylamide (AA) intake with the excretion of AA-related urinary mercapturic acids (MA), N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Excretion kinetics of these short-term exposure biomarkers were monitored under strictly controlled conditions within a duplicate diet human intervention study. One study arm (group A, n = 6) ingested AA via coffee (0.15-0.17 µg/kg bw) on day 6 and in a meal containing an upper exposure level of AA (14.1-15.9 μg/kg bw) on day 10. The other arm (group B) was on AA minimized diet (washout, 0.05-0.06 µg/kg bw) throughout the whole 13-day study period. On day 6, these volunteers ingested 13 C 3 D 3 -AA (1 μg/kg bw). In both arms, urinary MA excretion was continuously monitored and blood samples were taken to determine hemoglobin adducts. Ingestion of four cups of coffee resulted in a slightly enhanced short-term biomarker response within the background range of group B. At the end of the 13-day washout period, group B excreted an AAMA baseline level of 0.14 ± 0.10 µmol/d although AA intake was only about 0.06 µmol/d. This sustained over-proportional AAMA background suggested an endogenous AA baseline exposure level of 0.3-0.4 µg/kg bw/d. The excretion of 13 C 3 D 3 -AA was practically complete within 72-96 h which rules out delayed release of AA (or any other MA precursor) from deep body compartments. The results provide compelling support for the hypothesis of a sustained endogenous AA formation in the human body.

  15. FEASIBILITY AND EFFECTIVENESS OF DYADIC PROLONGED EXPOSURE INTERVENTION FOR PREVENTING POSTTRAUMATIC GRIEF IN YOUNG CHILDREN: A CASE REPORT OF TWO SIBLINGS.

    PubMed

    Rachamim, Lilach

    2017-09-01

    This article highlights the feasibility of a dyadic prolonged exposure (DPE) intervention (L. Rachamim, I. Mirochnik, L. Helpman, N. Nacasch, & E. Yadin, ) in a 3-year-old preschooler and in a 6-year-old kindergartener immediately following the traumatic death of their younger sibling. It presents a detailed case description of the DPE treatment addressing traumatic grief and includes transcribed treatment dialogue. At the time of treatment termination, both children and caregivers resumed normal functioning. The results suggest that DPE intervention may ameliorate posttraumatic grief symptoms in young children. Controlled studies of preventive interventions for this population are clearly warranted. © 2017 Michigan Association for Infant Mental Health.

  16. A multi-site single blind clinical study to compare the effects of prolonged exposure, eye movement desensitization and reprocessing and waiting list on patients with a current diagnosis of psychosis and co morbid post traumatic stress disorder: study protocol for the randomized controlled trial Treating Trauma in Psychosis

    PubMed Central

    2013-01-01

    Background Trauma contributes to psychosis and in psychotic disorders post-traumatic stress disorder (PTSD) is often a comorbid disorder. A problem is that PTSD is underdiagnosed and undertreated in people with psychotic disorders. This study’s primary goal is to examine the efficacy and safety of prolonged exposure and eye movement desensitization and reprocessing (EMDR) for PTSD in patients with both psychotic disorders and PTSD, as compared to a waiting list. Secondly, the effects of both treatments are determined on (a) symptoms of psychosis, in particular verbal hallucinations, (b) depression and social performance, and (c) economic costs. Thirdly, goals concern links between trauma exposure and psychotic symptomatology and the prevalence of exposure to traumatic events, and of PTSD. Fourthly predictors, moderators, and mediators for treatment success will be explored. These include cognitions and experiences concerning treatment harm, credibility and burden in both participants and therapists. Methods/Design A short PTSD-screener assesses the possible presence of PTSD in adult patients (21- to 65- years old) with psychotic disorders, while the Clinician Administered PTSD Scale interview will be used for the diagnosis of current PTSD. The M.I.N.I. Plus interview will be used for diagnosing lifetime psychotic disorders and mood disorders with psychotic features. The purpose is to include consenting participants (N = 240) in a multi-site single blind randomized clinical trial. Patients will be allocated to one of three treatment conditions (N = 80 each): prolonged exposure or EMDR (both consisting of eight weekly sessions of 90 minutes each) or a six-month waiting list. All participants are subjected to blind assessments at pre-treatment, twomonths post treatment, and six monthspost treatment. In addition, participants in the experimental conditions will have assessments at mid treatment and at 12 months follow-up. Discussion The results from the post

  17. Effects on respiratory homeostasis of prolonged, continuous hyperoxia at 1.5 to 3.0 ATA in man in Predictive Studies V

    NASA Technical Reports Server (NTRS)

    Gelfand, R.; Clark, J. M.; Lambertsen, C. J.; Pisarello, J. B.

    1987-01-01

    Prolonged exposures of men to continuous hyperoxia at 3.0, 2.5, 2.0, and 1.5 ATA were conducted to define CNS oxygen tolerance and to investigate the effects of prolonged hyperoxia on CNS and other organ functions. Altered respiratory homeostasis was evident during exposures of men to 2.5 and 3.0 ATA O2 as nonprogressive increment in ventilation and reciprocal decrement in PET(CO2). These changes were progressive during exposure at 1.5 ATA O2. Mean values of respiratory reactivity at CO2 were somewhat increased following prolonged hyperoxia at 1.5 and 2.5 ATA, compared to preexposure mean values. Hypoxic ventilatory response was unchanged or enhanced after oxygen exposures at 1.5 and 2.5 ATA. Observed respiratory and body temperature changes were not of sufficient magnitude to impair function.

  18. Subtleties in practical application of prolonged infusion of β-lactam antibiotics.

    PubMed

    De Waele, Jan J; Lipman, Jeffrey; Carlier, Mieke; Roberts, Jason A

    2015-05-01

    Prolonged infusion (PI) of β-lactam antibiotics is increasingly used in order to optimise antibiotic exposure in critically ill patients. Physicians are often not aware of a number of subtleties that may jeopardise the treatment. In this clinically based paper, we stress pragmatic issues, such as the importance of a loading dose before PI, and discuss a number of important practicalities that are mandatory to benefit from the pharmacokinetic advantages of prolonged β-lactam antibiotic administration. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  19. Bisphenol A Exposure and Cardiac Electrical Conduction in Excised Rat Hearts

    PubMed Central

    Jaimes, Rafael; Asfour, Huda; Swift, Luther M.; Wengrowski, Anastasia M.; Sarvazyan, Narine; Kay, Matthew W.

    2014-01-01

    Background: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. Objectives: The goal of our study was to measure the effect of BPA (0.1–100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. Methods: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Results: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1–100 μM BPA), prolonged action potential duration (1–100 μM BPA), and delayed atrioventricular conduction (10–100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Conclusions: Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA’s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations. Citation: Posnack NG, Jaimes R III, Asfour H

  20. Prolonged noise exposure-induced auditory threshold shifts in rats

    PubMed Central

    Chen, Guang-Di; Decker, Brandon; Muthaiah, Vijaya Prakash Krishnan; Sheppard, Adam; Salvi, Richard

    2014-01-01

    Noise-induced hearing loss (NIHL) initially increases with exposure duration, but eventually reaches an asymptotic threshold shift (ATS) once the exposure duration exceeds 18-24 h. Equations for predicting the ATS have been developed for several species, but not for rats, even though this species is extensively used in noise exposure research. To fill this void, we exposed rats to narrowband noise (NBN, 16-20 kHz) for 5 weeks starting at 80 dB SPL in the first week and then increasing the level by 6 dB per week to a final level of 104 dB SPL. Auditory brainstem responses (ABR) were recorded before, during, and following the exposure to determine the amount of hearing loss. The noise induced threshold shift to continuous long-term exposure, defined as compound threshold shift (CTS), within and above 16-20 kHz increased with noise level at the rate of 1.82 dB threshold shift per dB of noise level (NL) above a critical level (C) of 77.2 dB SPL i.e. CTS = 1.82(NL-77.2). The normalized amplitude of the largest ABR peak measured at 100 dB SPL decreased at the rate of 3.1% per dB of NL above the critical level of 76.9 dB SPL, i.e., %ABR Reduction = 3.1%(NL-76.9). ABR thresholds measured >30 days post-exposure only partially recovered resulting in a permanent threshold shift of 30-40 dB along with severe hair cell loss in the basal, high-frequency region of the cochlea. In the rat, CTS increases with noise level with a slope similar to humans and chinchillas. The critical level (C) in the rat is similar to that of humans, but higher than that of chinchillas. PMID:25219503

  1. A non-inferiority trial of Prolonged Exposure for posttraumatic stress disorder: In person versus home-based telehealth.

    PubMed

    Acierno, Ron; Knapp, Rebecca; Tuerk, Peter; Gilmore, Amanda K; Lejuez, Carl; Ruggiero, Kenneth; Muzzy, Wendy; Egede, Leonard; Hernandez-Tejada, Melba A; Foa, Edna B

    2017-02-01

    This is the first randomized controlled trial to evaluate non-inferiority of Prolonged Exposure (PE) delivered via home-based telehealth (HBT) compared to standard in-person (IP) PE. One-hundred thirty two Veterans recruited from a Southeastern Veterans Affairs Medical Center and affiliated University who met criteria for posttraumatic stress disorder (PTSD) were randomized to receive PE via HBT or PE via IP. Results indicated that PE-HBT was non-inferior to PE-IP in terms of reducing PTSD scores at post-treatment, 3 and 6 month follow-up. However, non-inferiority hypotheses for depression were only supported at 6 month follow-up. HBT has great potential to reduce patient burden associated with receiving treatment in terms of travel time, travel cost, lost work, and stigma without sacrificing efficacy. These findings indicate that telehealth treatment delivered directly into patients' homes may dramatically increase the reach of this evidence-based therapy for PTSD without diminishing effectiveness. Published by Elsevier Ltd.

  2. Infection prevention and control during prolonged human space travel.

    PubMed

    Mermel, Leonard A

    2013-01-01

    Prolonged human spaceflight to another planet or an asteroid will introduce unique challenges of mitigating the risk of infection. During space travel, exposure to microgravity, radiation, and stress alter human immunoregulatory responses, which can in turn impact an astronaut's ability to prevent acquisition of infectious agents or reactivation of latent infection. In addition, microgravity affects virulence, growth kinetics, and biofilm formation of potential microbial pathogens. These interactions occur in a confined space in microgravity, providing ample opportunity for heavy microbial contamination of the environment. In addition, there is the persistence of aerosolized, microbe-containing particles. Any mission involving prolonged human spaceflight must be carefully planned to minimize vulnerabilities and maximize the likelihood of success.

  3. Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

    PubMed

    Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

    2017-01-01

    Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, p<0,001) and PTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, p<0.001) showed significant improvement from baseline to final session. Longitudinal seizure follow up in 14 patients revealed that gains made on the final session were maintained at follow-up (Z=-1.069 p=0.285). Prolonged exposure therapy for patients dually diagnosed with PNES and PTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Value of Formalin Fixation for the Prolonged Preservation of Rodent Myocardial Microanatomical Organization: Evidence by MR Diffusion Tensor Imaging.

    PubMed

    Giannakidis, Archontis; Gullberg, Grant T; Pennell, Dudley J; Firmin, David N

    2016-07-01

    Previous ex vivo diffusion tensor imaging (DTI) studies on formalin-fixed myocardial tissue assumed that, after some initial changes in the first 48 hr since the start of fixation, DTI parameters remain stable over time. Prolonged preservation of cardiac tissue in formalin prior to imaging has been seen many times in the DTI literature as it is considered orderly. Our objective is to define the effects of the prolonged cardiac tissue exposure to formalin on tissue microanatomical organization, as this is assessed by DTI parameters. DTI experiments were conducted on eight excised rodent hearts that were fixed by immersion in formalin. The samples were randomly divided into two equinumerous groups corresponding to shorter (∼2 weeks) and more prolonged (∼6-8 weeks) durations of tissue exposure to formalin prior to imaging. We found that when the duration of cardiac tissue exposure to formalin before imaging increased, water diffusion became less restricted, helix angle (HA) histograms flattened out and exhibited heavier tails (even though the classic HA transmural variation was preserved), and a significant loss of inter-voxel primary diffusion orientation integrity was introduced. The prolonged preservation of cardiac tissue in formalin profoundly affected its microstructural organization, as this was assessed by DTI parameters. The accurate interpretation of diffusivity profiles necessitates awareness of the pitfalls of prolonged cardiac tissue exposure duration to formalin. The acquired knowledge works to the advantage of a proper experimental design of DTI studies of fixed hearts. Anat Rec, 299:878-887, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Infants' Background Television Exposure during Play: Negative Relations to the Quantity and Quality of Mothers' Speech and Infants' Vocabulary Acquisition

    ERIC Educational Resources Information Center

    Masur, Elise Frank; Flynn, Valerie; Olson, Janet

    2016-01-01

    Research on immediate effects of background television during mother-infant toy play shows that an operating television in the room disrupts maternal communicative behaviors crucial for infants' vocabulary acquisition. This study is the first to examine associations between frequent background TV/video exposure during mother-infant toy play at…

  6. Factors on working conditions and prolonged fatigue among physicians in Japan.

    PubMed

    Wada, Koji; Arimatsu, Mayuri; Yoshikawa, Toru; Oda, Susumu; Taniguchi, Hatsumi; Higashi, Toshiaki; Aizawa, Yoshiharu

    2008-10-01

    Fatigue among physicians could affect patients' safety and physicians' health. Fatigue could be caused by unfavorable working conditions. However, there have been no studies on the working conditions and fatigue among physicians in Japan. The objective of this study was to determine the factors on working conditions associated with prolonged fatigue among physicians in Japan. A questionnaire was mailed to physicians who graduated from one of the medical schools in Japan and who have had more than 3 years of experience in clinical practice. They were asked to assess 10 different aspects of their working conditions using a 5-point Likert scale. Prolonged fatigue was measured using the checklist of individual strength questionnaire. Multiple regression analysis was used to examine the multivariate relationship between the variables and prolonged fatigue. Data from 377 men and 101 women were analyzed in this study. For both male and female physicians, a harder workload was positively associated and better career satisfaction was negatively associated with prolonged fatigue. Prolonged fatigue was negatively associated with better relationships with other physicians and staff for male physicians and less personal time for female physicians. The adjusted variance in prolonged fatigue related to exposure variables was 26 and 29% in men and in women, respectively. The result of this study suggested that it is desirable to take these factors into consideration in the management of prolonged fatigue among physicians in Japan.

  7. [Causation between occupational prolonged standing time during progestation and pregnancy related complications].

    PubMed

    Weng, Ting-ting; Xu, Ye-qing; Yan, Shuang-qin; Pan, Wei-jun; Tao, Fang-biao

    2013-06-01

    To describe the epidemiological characteristics of profession related long-standing behavior during preconception and progestation, and to probe the relationship between prolonged standing jobs and the common pregnancy related complications among pregnant women, in Ma' anshan city,Anhui province. In this cohort study, subjects who had their first antenatal examination at Ma' anshan Maternal and Child Care Centers were recruited under informed consent, from October 2008 to October 2010. All the information were collected through questionnaires in the first, second and third trimesters respectively. Three questionnaires were filled in by subjects under the guidance of healthcare takers. In the study, the 75(th) percentile of prolonged-standing times were 4.0 h/d and 3.0 h/d respectively in preconception and progestation. The characteristics of pregnant women with low social/economic status, prone to be involved in stand-long occupation. Results in logistic regression analysis, prolonged-standing jobs during preconception was the risk factor of pregnancy-induced hypertension and severe anemia. The adjusted odds ratios were 2.05 (95%CI:1.26-3.31) and 1.38(95%CI:1.03-1.85)respectively. Prolonged standing jobs appeared to be common occupational exposure to and risks of both pregnant woman and their fetus. Exposure to these kinds of jobs during preconception could increase the risk of pregnancy-induced hypertension and severe anemia. In order to promote maternal health programs, all the related occupational risk factors should be valued and avoided during preconception and pregnancy.

  8. Public exposure due to external gamma background radiation in boundary areas of Iran.

    PubMed

    Pooya, S M Hosseini; Dashtipour, M R; Enferadi, A; Orouji, T

    2015-09-01

    A monitoring program in boundary areas of a country is an appropriate way to indicate the level of public exposure. In this research, gamma background radiation was measured using TL dosimeters at 12 boundary areas as well as in the capital city of Iran during the period 2010 to 2011. The measurements were carried out in semi-annual time intervals from January to June and July to December in each year. The maximum average dose equivalent value measured was approximately 70 μSv/month for Tehran city. Also, the average dose values obtained were less than 40 μSv/month for all the cities located at the sea level except that of high level natural radiation area of Ramsar, and more than 55 μSv/month for the higher elevation cities. The public exposure due to ambient gamma dose equivalent in Iran is within the levels reported by UNSCEAR. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Changes in background impair fluency-triggered positive affect: a cross-cultural test using a mere-exposure paradigm.

    PubMed

    Ishii, Keiko

    2011-04-01

    This study examined whether repeated exposure would enhance positive evaluations when only a part of a stimulus (e.g., the central object) was identical to a previously presented stimulus. Japanese and American participants were exposed to photographs of animals with scenery, then asked their preferences for each of four types of photographs of animals (photographs of animals with the original scenery, photographs of animals without scenery, photographs of animals with novel scenery, and photographs of animals not depicted previously). Finally, their recognition of the animals presented in the exposure phase was tested. Members of both groups showed the mere-exposure effect for the first two types of stimuli, irrespective of stimulus recognition accuracy, whereas this effect was not observed for animals presented with novel scenery. This suggests that changes in background impair positive affect as a result of repeated exposure.

  10. Neural circuits via which single prolonged stress exposure leads to fear extinction retention deficits

    PubMed Central

    Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions critical for extinction retention (i.e., fear extinction circuit). These were the ventral hippocampus (vHipp), dorsal hippocampus (dHipp), basolateral amygdala (BLA), prelimbic cortex (PL), and infralimbic cortex (IL). SPS or control rats were fear conditioned then subjected to extinction training and testing. Subsets of rats were euthanized after extinction training, extinction testing, or immediate removal from the housing colony (baseline condition) to assay c-Fos levels (measure of neural activity) in respective brain region. SPS induced extinction retention deficits. During extinction training SPS disrupted enhanced IL neural activity and inhibited BLA neural activity. SPS also disrupted inhibited BLA and vHipp neural activity during extinction testing. Statistical analyses suggested that SPS disrupted functional connectivity within the dHipp during extinction training and increased functional connectivity between the BLA and vHipp during extinction testing. Our findings suggest that SPS induces extinction retention deficits by disrupting both excitatory and inhibitory changes in neural activity within the fear extinction circuit and inducing changes in functional connectivity within the Hipp and BLA. PMID:27918273

  11. Acceptability of prolonged exposure therapy among U.S. Iraq war veterans with PTSD symptomology.

    PubMed

    Kehle-Forbes, Shannon M; Polusny, Melissa A; Erbes, Christopher R; Gerould, Heather

    2014-08-01

    Despite efforts to increase the availability of prolonged exposure therapy (PE) within the Department of Veterans Affairs, little is known about the acceptability of PE among veteran populations. We queried a sample of 58 U.S. National Guard Iraq War veterans previously deployed to combat who screened positive for posttraumatic stress disorder (PTSD) as to whether they would prefer PE, treatment with an antidepressant, or no treatment. We also gathered open-ended responses regarding the veterans' reasons for their choice and potential barriers to engaging in that treatment. A majority (53.4%) of veterans who completed the interview said they would choose to participate in PE, 36.2% preferred antidepressant treatment, 8.6% chose no treatment, and 1.8% were unable to choose among the options. Credibility of the treatment rationale and beliefs about the treatment's efficacy were the most frequently given reasons for choosing PE (45.2%); past treatment experience was the most common reason for choosing antidepressant treatment (47.6%). The most commonly cited barrier for those who chose both antidepressant treatment and PE was time to participate (52.4% and 77.4%, respectively). The findings suggest that PE is a credible and acceptable treatment option for veterans with PTSD symptomology. Published 2014. This article is a US Government work and is in the public domain in the USA.

  12. Alterations in the programming of energy metabolism in adolescents with background exposure to dioxins, dl-PCBs and PBDEs

    PubMed Central

    Koppe, Janna G.; Vulsma, Thomas; Olie, Kees; van Aalderen, Wim M. C.; de Voogt, Pim; Legler, Juliette; ten Tusscher, Gavin W.

    2017-01-01

    Objectives Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. Study design In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS. Results Prenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI. Discussion/Conclusion This study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level. PMID:28898241

  13. Alterations in the programming of energy metabolism in adolescents with background exposure to dioxins, dl-PCBs and PBDEs.

    PubMed

    Leijs, Marike M; Koppe, Janna G; Vulsma, Thomas; Olie, Kees; van Aalderen, Wim M C; de Voogt, Pim; Legler, Juliette; Ten Tusscher, Gavin W

    2017-01-01

    Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS. Prenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI. This study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level.

  14. Prenatal nicotinic exposure prolongs superior laryngeal C-fiber-mediated apnea and bradycardia through enhancing neuronal TRPV1 expression and excitation.

    PubMed

    Gao, Xiuping; Zhao, Lei; Zhuang, Jianguo; Zang, Na; Xu, Fadi

    2017-10-01

    Maternal cigarette smoke, including prenatal nicotinic exposure (PNE), is responsible for sudden infant death syndrome (SIDS). The fatal events of SIDS are characterized by severe bradycardia and life-threatening apneas. Although activation of transient receptor potential vanilloid 1 (TRPV1) of superior laryngeal C fibers (SLCFs) could induce bradycardia and apnea and has been implicated in SIDS pathogenesis, how PNE affects the SLCF-mediated cardiorespiratory responses remains unexplored. Here, we tested the hypothesis that PNE would aggravate the SLCF-mediated apnea and bradycardia via up-regulating TRPV1 expression and excitation of laryngeal C neurons in the nodose/jugular (N/J) ganglia. To this end, we compared the following outcomes between control and PNE rat pups at postnatal days 11-14: 1 ) the cardiorespiratory responses to intralaryngeal application of capsaicin (10 µg/ml, 50 µl), a selective stimulant for TRPV1 receptors, in anesthetized preparation; 2 ) immunoreactivity and mRNA of TRPV1 receptors of laryngeal sensory C neurons in the N/J ganglia retrogradely traced by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate; and 3 ) TRPV1 currents and electrophysiological characteristics of these neurons by using whole-cell patch-clamp technique in vitro Our results showed that PNE markedly prolonged the apneic response and exacerbated the bradycardic response to intralaryngeal perfusion of capsaicin, which was associated with up-regulation of TRPV1 expression in laryngeal C neurons. In addition, PNE increased the TRPV1 currents, depressed the slow delayed rectifier potassium currents, and increased the resting membrane potential of these neurons. Our results suggest that PNE is capable of aggravating the SLCF-mediated apnea and bradycardia through TRPV1 sensitization and neuronal excitation, which may contribute to the pathogenesis of SIDS.-Gao, X., Zhao, L., Zhuang, J., Zang, N., Xu, F. Prenatal nicotinic exposure prolongs superior

  15. Community Use of Intranasal Midazolam for Managing Prolonged Seizures

    ERIC Educational Resources Information Center

    Kyrkou, Margaret; Harbord, Michael; Kyrkou, Nicole; Kay, Debra; Coulthard, Kingsley

    2006-01-01

    Background: Until a few years ago, rectal diazepam (RD) was the only option available to parents and carers managing prolonged seizures. However, its use in the community was limited due to the requirement for privacy, and because education staff in South Australia are not permitted to carry out invasive procedures. Method: Following a literature…

  16. “How Will It Help Me?”: Reasons Underlying Treatment Preferences Between Sertraline and Prolonged Exposure in PTSD

    PubMed Central

    Chen, Jessica A.; Keller, Stephanie M.; Zoellner, Lori A.; Feeny, Norah C.

    2014-01-01

    Individuals with posttraumatic stress disorder (PTSD) often wait years before seeking treatment. Improving treatment initiation and adherence requires a better understanding patient beliefs that lead to treatment preferences. Using a treatment-seeking sample (N = 200) with chronic PTSD, qualitative reasons underlying treatment preferences for either prolonged exposure (PE) or sertraline (SER) were examined. Reasons for treatment preference primarily focused on how the treatment was perceived to reduce PTSD symptoms rather than practical ones. Patients were more positive about PE than SER. Individual differences did not reliably predict underlying preference reasons, suggesting that what makes a treatment desirable is not strongly determined by current functioning, treatment, or trauma history. Taken together, this information is critical for treatment providers, arguing for enhancing psychoeducation about how treatment works and acknowledging pre-existing biases against pharmacotherapy for PTSD that should be addressed. This knowledge has the potential to optimize and better personalize PTSD patient care. PMID:23896851

  17. Reinventing the Wheel: Impact of Prolonged Antibiotic Exposure on Multi-Drug Resistant Ventilator-Associated Pneumonia in Trauma Patients.

    PubMed

    Lewis, Richard H; Sharpe, John P; Swanson, Joseph M; Fabian, Timothy C; Croce, Martin A; Magnotti, Louis J

    2018-04-16

    Multi-drug resistant (MDR) strains of both Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PA) as causative VAP pathogens are becoming increasingly common. Still, the risk factors associated with this increased resistance have yet to be elucidated. The purpose of this study was to examine the changing sensitivity patterns of these pathogens over time and determine which risk factors predict MDR in trauma patients with VAP. Patients with either AB or PA VAP over 10 years were stratified by pathogen sensitivity (sensitive (SEN) and MDR), age, severity of shock and injury severity. Prophylactic and empiric antibiotic days, risk factors for severe VAP and mortality were compared. Multivariable logistic regression (MLR) was performed to determine which risk factors were independent predictors of MDR. 397 patients were identified with AB or PA VAP. There were 173 episodes of AB (91 SEN and 82 MDR) and 224 episodes of PA (170 SEN and 54 MDR). The incidence of MDR VAP did not change over the study (p=0.633). Groups were clinically similar with the exception of 24-hour transfusions (14 vs 19 units, p = 0.009) and extremity AIS (1 vs 3, p<0.001), both significantly increased in the MDR group. Antibiotic exposure as well as mIEAT (63% vs 81%, p<0.001) were significantly increased in the MDR group. MLR identified prophylactic antibiotic days (OR 23.1; 95%CI 16.7-28, p<0.001) and mIEAT (OR 18.1; 95%CI 12.2-26.1, p=0.001) as independent predictors of MDR after adjusting for severity of shock, injury severity, severity of VAP and antibiotic exposure. Prolonged exposure to unnecessary antibiotics remains one of the strongest predictors for the development of antibiotic resistance. MLR identified prophylactic antibiotic days and mIEAT an independent risk factors for MDR VAP. Thus, limiting prophylactic antibiotic days is the only potentially modifiable risk factor for the development of MDR VAP in trauma patients. Level III, Prognostic LEVEL OF EVIDENCE: Multi

  18. Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival.

    PubMed

    Jin, Xiangyuan; Uchiyama, Masateru; Zhang, Qi; Niimi, Masanori

    2014-05-09

    Herbal medicines have unique odors, and the act of smelling may have modulatory effects on the immune system. We investigated the effect of olfactory exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune responses in a murine model of cardiac allograft transplantation. Naïve or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart and were exposed to the odor of TJ-23 until rejection. Some naïve CBA recipients of an allograft were given olfactory exposure to Sairei-to (TJ-114), trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation lacking one component. Adoptive transfer studies were performed to determine whether regulatory cells were generated. Untreated CBA mice rejected their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure to TJ-23 had significantly prolonged allograft survival, whereas those exposed to the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did not. Secondary allograft recipients that were given, at 30 days after transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from primary recipients exposed to the odor of TJ-23 had indefinitely prolonged allograft survival. Prolonged survival of cardiac allografts and generation of regulatory cells was associated with exposure to the odor of TJ-23 in our model. The olfactory area of the brain may have a role in the modulation of immune responses.

  19. Changes in Negative Cognitions Mediate PTSD Symptom Reductions During Client-Centered Therapy and Prolonged Exposure for Adolescents

    PubMed Central

    McLean, Carmen P.; Yeh, Rebecca; Rosenfield, David; Foa, Edna B.

    2015-01-01

    Objective To assess whether changes in negative trauma-related cognitions play an important role in reducing symptoms of posttraumatic stress disorder (PTSD) and depression during prolonged exposure therapy for adolescents (PE-A). Method Secondary analysis of data from a randomized controlled trial comparing PE-A with client-centered therapy (CCT) for PTSD. Participants were 61 adolescent female sexual assault survivors ages 13–18 who received 8–14 weekly sessions of PE-A or CCT at a community rape crisis center. PTSD severity was assessed at baseline, mid-treatment, post-treatment, and 3-months post-treatment. Participants also completed self-report measures of negative posttraumatic cognitions and depressive symptoms at the same assessment points. Results Cross lag panel mediation analyses showed that change in negative trauma-related cognitions mediated change in PTSD symptoms and depressive symptoms whereas change in PTSD and depressive symptoms did not mediate change in negative cognitions. Conclusion Our findings support EPT and suggest that change in negative trauma-related cognitions is a mechanism of both PE-A and CCT. PMID:25812826

  20. TISSUE CONCENTRATION OF PCBS IN ANIMAL EXPERIMENTS AS COMPARED WITH THOSE IN HUMANS WITH BACKGROUND-LEVEL EXPOSURE

    EPA Science Inventory

    TISSUE CONCENTRATION OF PCBS IN ANIMAL EXPERIMENTS AS COMPARED WITH THOSE IN HUMANS WITH BACKGROUND-LEVEL EXPOSURE. M J DeVito1 and M P Longnecker2. 1NHEERL, ORD, USEPA; Research Triangle Park, NC, USA; 2Epidemiology
    Branch, NIEHS, Research Triangle Park, NC, USA.

    To ...

  1. Does prolonged cyanide exposure have a diabetogenic effect?

    PubMed

    Soto-Blanco, B; Sousa, A B; Manzano, H; Guerra, J L; Górniak, S L

    2001-04-01

    Cyanide exposure through cassava consumption has been associated with the development of malnutrition-related diabetes mellitus (MRDM). However, there are few experimental reproductions of this disease. In the present study 42 rats received 0, 9.0 or 12.0 mg KCN/kg bw/d for 15 d, 26 pigs were dosed with 0, 2.0, 4.0 or 6.0 mg KCN/kg for 74 d, and 34 goats received 0, 0.3, 0.6, 1.2 or 3.0 mg KCN/kg for 5 mo. At the end of each experimental period, plasma samples were obtained for glucose and thiocyanate measurement, and the pancreas was collected for histopathologic study. No significant differences in plasma glucose concentrations occurred between groups. The pancreas had no pathology. Chronic cyanide exposure did not promote diabetogenic effects in rats, swine or goats, suggesting that cyanide is not responsible for MRDM in humans.

  2. Prolonged Cough in Pediatric Population First Line Care, Belgian Guidelines

    PubMed Central

    Leconte, Sophie; Valentin, Stéphanie; Dromelet, Estelle; De Jonghe, Michel

    2017-01-01

    Background: The clinical approach to a prolonged cough, i.e. a cough lasting more than three weeks, is challenging for general practitioners as well for primary care pediatricians. What the recommended clinical approach in primary care is, how cough duration or cough characteristics impact the diagnosis, and what the efficiency and safety of antibiotics or symptomatic treatments are remain in question for primary care physicians. Objective: The last Belgian guidelines were published in 2006 and needed to be reviewed. Those background questions were used to conduct our guideline updating procedure. Methods: We systematically performed a pyramidal literature search between the periods 2006-2014 in order to write evidence based guidelines. The data of the literature was summarized, discussed by the authors, experts and the Belgian primary care guidelines committee. Recommendations were formulated and scored following the GRADE classification. Results: The consultation history as well as the physical examination should be directed towards searching for warning signs (GRADE 1B) and towards the common etiologies depending on cough duration (GRADE 2C). If the cough lasts for more than eight weeks, chest radiography and spirometry should be considered (GRADE 2C). An antibiotic is recommended for a prolonged wet cough (over eight weeks) if prolonged bacterial bronchitis is suspected (GRADE 1B). In the absence of clinical signs of a specific etiology of a cough, no drug can be recommended (GRADE 1B). For all cases, it is initially suggested to avoid irritants (GRADE 1C) as well as to take into account the concerns of parents and inform them about the natural development of a cough. Conclusions: More research is needed to provide evidence on the clinical pathway on prolonged cough for primary care. Cough duration of more than eight weeks and prolonged wet cough are the most useful cough characteristics. Regarding a specific cough treatment, no medication has proved any effect

  3. Effectiveness of Prolonged Exposure and Cognitive Processing Therapy for U.S. Veterans With a History of Traumatic Brain Injury.

    PubMed

    Ragsdale, Katie A; Voss Horrell, Sarah C

    2016-10-01

    This retrospective analysis of previously existing nonrandomized clinical data examined the effectiveness of completing prolonged exposure (PE) or cognitive processing therapy (CPT) in a sample of 41 U.S. veterans at a Veterans Affairs medical center. The sample included 19 veterans with diagnoses of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and 22 veterans with PTSD only. Diagnostic groups did not significantly differ on PTSD and depression symptom reduction, F(2, 36) = 0.05, p = .951; Pillai's trace = 0.00, partial η 2 = .00. Veterans who completed PE showed greater symptom reduction than those who completed CPT, F(2, 36) = 12.10, p < .001; Pillai's trace = 0.40, partial η 2 = .40, regardless of TBI status. Overall, our results suggested that TBI status should not preclude individuals from being offered trauma-focused PTSD treatment. Copyright © 2016 International Society for Traumatic Stress Studies.

  4. Neural circuits via which single prolonged stress exposure leads to fear extinction retention deficits.

    PubMed

    Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; Keller, Samantha M; DePietro, Thomas

    2016-12-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions critical for extinction retention (i.e., fear extinction circuit). These were the ventral hippocampus (vHipp), dorsal hippocampus (dHipp), basolateral amygdala (BLA), prelimbic cortex (PL), and infralimbic cortex (IL). SPS or control rats were fear conditioned then subjected to extinction training and testing. Subsets of rats were euthanized after extinction training, extinction testing, or immediate removal from the housing colony (baseline condition) to assay c-Fos levels (measure of neural activity) in respective brain region. SPS induced extinction retention deficits. During extinction training SPS disrupted enhanced IL neural activity and inhibited BLA neural activity. SPS also disrupted inhibited BLA and vHipp neural activity during extinction testing. Statistical analyses suggested that SPS disrupted functional connectivity within the dHipp during extinction training and increased functional connectivity between the BLA and vHipp during extinction testing. Our findings suggest that SPS induces extinction retention deficits by disrupting both excitatory and inhibitory changes in neural activity within the fear extinction circuit and inducing changes in functional connectivity within the Hipp and BLA. © 2016 Knox et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Effect of leucine supplementation on fat free mass with prolonged hypoxic exposure during a 13-day trek to Everest Base Camp: a double-blind randomized study.

    PubMed

    Wing-Gaia, Stacie L; Gershenoff, Dana C; Drummond, Micah J; Askew, E Wayne

    2014-03-01

    Loss of body weight and fat-free mass (FFM) are commonly noted with prolonged exposure to hypobaric hypoxia. Recent evidence suggests protein supplementation, specifically leucine, may potentially attenuate loss of FFM in subcaloric conditions during normoxia. The purpose of this study was to determine if leucine supplementation would prevent the loss of FFM in subcaloric conditions during prolonged hypoxia. Eighteen physically active male (n = 10) and female (n = 8) trekkers completed a 13-day trek in Nepal to Everest Base Camp with a mean altitude of 4140 m (range 2810-5364 m). In this double-blind study, participants were randomized to ingest either leucine (LEU) (7 g leucine, 93 kcal, 14.5 g whey-based protein) or an isocaloric isonitrogenous control (CON) (0.3 g LEU, 93 kcal, 11.3 g collagen protein) twice daily prior to meals. Body weight, body composition, and circumferences of bicep, thigh, and calf were measured pre- and post-trek. There was a significant time effect for body weight (-2.2% ± 1.7%), FFM (-1.7% ± 1.5%), fat mass (-4.0% ± 6.9%), and circumferences (p < 0.05). However, there was no treatment effect on body weight (CON -2.3 ± 2.0%; LEU -2.2 ± 1.5%), FFM (CON -2.1 ± 1.5%; LEU -1.2 ± 1.6%), fat mass (CON -2.9% ± 5.9%; LEU -5.4% ± 8.1%), or circumferences. Although a significant loss of body weight, FFM, and fat mass was noted in 13 days of high altitude exposure, FFM loss was not attenuated by leucine. Future studies are needed to determine if leucine attenuates loss of FFM with longer duration high altitude exposure.

  6. Pre-treatment Predictors of Dropout from Prolonged Exposure Therapy in Patients with Chronic Posttraumatic Stress Disorder and Comorbid Substance Use Disorders

    PubMed Central

    Belleau, Emily L.; Chin, Eu Gene; Wanklyn, Sonya G.; Zambrano-Vazquez, Laura; Schumacher, Julie A.; Coffey, Scott F.

    2017-01-01

    Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) are commonly co-occurring disorders associated with more adverse consequences than PTSD alone. Prolonged exposure therapy (PE) is one of the most efficacious treatments for PTSD. However, among individuals with PTSD-SUD, 35–62% of individuals drop out of trauma-focused exposure treatments. Thus, it is important to identify predictors of PTSD treatment dropout among substance abusers with PTSD in order to gain information about adapting treatment strategies to enhance retention and outcomes. The current study explored pre-treatment predictors of early termination from PE treatment in a sample of 85 individuals receiving concurrent treatment for PTSD and a SUD in a residential treatment facility as part of a randomized controlled trial. The results indicated that less education and more anxiety sensitivity uniquely predicted PE treatment dropout. Demographic variables, PTSD severity, SUD severity, mental health comorbidities, and emotion regulation difficulties did not predict treatment dropout. These results suggest that adding pre-treatment interventions that address anxiety sensitivity, and promote social adjustment and cognitive flexibility, could possibly improve PE retention rates in clients with high anxiety or low education. PMID:28147254

  7. Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990-2009.

    PubMed

    Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

    2017-04-01

    Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland.

  8. Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction.

    PubMed

    Arjomandi, Mehrdad; Zeng, Siyang; Geerts, Jeroen; Stiner, Rachel K; Bos, Bruce; van Koeverden, Ian; Keene, Jason; Elicker, Brett; Blanc, Paul D; Gold, Warren M

    2018-01-01

    Exposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV 1 /FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear. To investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry. We elicited symptom prevalence by structured questionnaires, examined functional capacity (maximum oxygen uptake, VO 2max ) by exercise testing, and estimated associations of those outcomes with air trapping (plethysmography-measured residual volume-to-total lung capacity ratio, RV/TLC), and progressive air trapping with exertion (increase in fraction of tidal breathing that is flow limited on expiration during exercise (per cent of expiratory flow limitation, %EFL)). RV/TLC was within the predicted normal limits, but was highly variable spanning 22%±13% and 16%±8% across the increments of FEV 1 /FVC and FEV 1 , respectively. Respiratory complaints were prevalent (50.4%) with the most common symptom being ≥2 episodes of cough per year (44.5%). Higher RV/TLC was associated with higher OR of reporting respiratory symptoms (n=256; r 2 =0.03; p=0.011) and lower VO 2max (n=179; r 2 =0.47; p=0.013), and %EFL was negatively associated with VO 2max (n=32; r 2 =0.40; p=0.017). In those at risk for obstruction due to SHS exposure but with preserved spirometry, higher RV/TLC identifies a subgroup with increased respiratory symptoms and lower exercise capacity.

  9. Utilizing Telehealth to Support Treatment of Acute Stress Disorder in a Theater of War: Prolonged Exposure via Clinical Videoconferencing.

    PubMed

    Pelton, Dan; Wangelin, Bethany; Tuerk, Peter

    2015-05-01

    Posttraumatic stress disorder (PTSD) and acute stress disorder are prevalent mental health diagnoses associated with the military operations in Iraq and Afghanistan and are especially significant in service members returning from combat. Prolonged exposure (PE) therapy is a highly effective behavioral treatment for these symptoms, and providing this treatment as soon as possible, even in the midst of a soldier's combat deployment, has strong potential benefits. In the current case study, telehealth technology was used to support the delivery of PE therapy to treat a service member diagnosed with acute stress disorder in a war zone. PE was conducted face-to-face on the relatively secure Forward Operating Base for the first half of therapy and via clinical videoconferencing (CV) to the service member's remote combat outpost during the later stages of therapy. The service member exhibited marked improvements in symptoms over 10 sessions. Results are consistent with previous empirical findings and highlight the potential benefits of using telehealth to deliver evidenced-based treatment for traumatic stress disorders in a war zone. This case study provides a preliminary working model for delivering PE in a combat environment using multiple delivery systems. Benefits and clinical utility of CV-delivered exposure therapy are discussed, particularly for providers pending future operational deployments (e.g., including members of the military, independent government agencies, and first responders) and for those treating patients in remote locations.

  10. Ventricular Cycle Length Characteristics Estimative of Prolonged RR Interval during Atrial Fibrillation

    PubMed Central

    CIACCIO, EDWARD J.; BIVIANO, ANGELO B.; GAMBHIR, ALOK; EINSTEIN, ANDREW J.; GARAN, HASAN

    2014-01-01

    Background When atrial fibrillation (AF) is incessant, imaging during a prolonged ventricular RR interval may improve image quality. It was hypothesized that long RR intervals could be predicted from preceding RR values. Methods From the PhysioNet database, electrocardiogram RR intervals were obtained from 74 persistent AF patients. An RR interval lengthened by at least 250 ms beyond the immediately preceding RR interval (termed T0 and T1, respectively) was considered prolonged. A two-parameter scatterplot was used to predict the occurrence of a prolonged interval T0. The scatterplot parameters were: (1) RR variability (RRv) estimated as the average second derivative from 10 previous pairs of RR differences, T13–T2, and (2) Tm–T1, the difference between Tm, the mean from T13 to T2, and T1. For each patient, scatterplots were constructed using preliminary data from the first hour. The ranges of parameters 1 and 2 were adjusted to maximize the proportion of prolonged RR intervals within range. These constraints were used for prediction of prolonged RR in test data collected during the second hour. Results The mean prolonged event was 1.0 seconds in duration. Actual prolonged events were identified with a mean positive predictive value (PPV) of 80% in the test set. PPV was >80% in 36 of 74 patients. An average of 10.8 prolonged RR intervals per 60 minutes was correctly identified. Conclusions A method was developed to predict prolonged RR intervals using two parameters and prior statistical sampling for each patient. This or similar methodology may help improve cardiac imaging in many longstanding persistent AF patients. PMID:23998759

  11. What would you choose? Sertraline or prolonged exposure in community and PTSD treatment seeking women.

    PubMed

    Feeny, Norah C; Zoellner, Lori A; Mavissakalian, Matig R; Roy-Byrne, Peter P

    2009-01-01

    Both sertraline (SER) and prolonged exposure (PE) are empirically supported treatments for chronic posttraumatic stress disorder (PTSD). While efficacious, these treatments are quite different in approach, and such differences may influence both treatment choice and treatment outcome. To date, we know very little about the relative efficacy of pharmacological and psychological treatments for chronic PTSD. In Study 1, we compared rates of treatment choice (SER or PE) in 74 trauma-exposed women. In Study 2, we extended this work to an open-choice treatment trial, in which 31 female assault survivors with chronic PTSD received their choice of SER or PE for ten weeks and were followed over time. In Study 1 (82%) and Study 2 (74.2%), the majority of women chose PE. In Study 2, both SER and PE evidenced moderate to large unadjusted effect sizes, with evidence of an advantage for PE in propensity adjusted analyses at posttreatment. Women with co-occurring major depressive disorder (MDD) were more likely to choose SER than those without MDD. However, among those with MDD, the advantage of PE was particularly evident. Our results highlight the presence of clear treatment preferences for PTSD and their potential impact on outcome. This study underscores the importance of systematic study of patient preferences and encourages a rethinking of one-size fits all approaches to treatment for mental disorders. (c) 2009 Wiley-Liss, Inc.

  12. Implementation outcomes of military provider training in cognitive processing therapy and prolonged exposure therapy for post-traumatic stress disorder.

    PubMed

    Borah, Elisa V; Wright, Edward C; Donahue, D Allen; Cedillos, Elizabeth M; Riggs, David S; Isler, William C; Peterson, Alan L

    2013-09-01

    Between 2006 and 2012, the Department of Defense trained thousands of military mental health providers in the use of evidence-based treatments for post-traumatic stress disorder. Most providers were trained in multiday workshops that focused on the use of Cognitive Processing Therapy and Prolonged Exposure. This study is a follow-up evaluation of the implementation practices of 103 Air Force mental health providers. A survey was administered online to workshop participants; 34.2% of participants responded. Findings on treatment implementation with the providers indicated that a majority of respondents found the trainings valuable and were interested in using the treatments, yet they reported a lack of time in their clinic appointment structure to support their use. Insufficient supervision was also cited as a barrier to treatment use. Results suggest the need to improve strategies for implementing evidence-based practices with providers to enhance clinical outcomes in military settings. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

  13. Does background postnatal methyl mercury exposure in toddlers affect cognition and behavior?

    PubMed

    Cao, Yang; Chen, Aimin; Jones, Robert L; Radcliffe, Jerilynn; Caldwell, Kathleen L; Dietrich, Kim N; Rogan, Walter J

    2010-01-01

    Because the toxicological effects of mercury (Hg) are more serious in the developing central nervous system of children than adults, there are growing concerns about prenatal and early childhood Hg exposure. This study examined postnatal methylmercury (MeHg) exposure and cognition and behavior in 780 children enrolled in the Treatment of Lead (Pb)-exposed Children clinical trial (TLC) with 396 children allocated to the succimer and 384 to the placebo groups. Mercury exposure was determined from analyses of blood drawn 1 week before randomization and 1 week after treatment began when succimer had its maximal effect on blood Pb (PbB). The baseline MeHg concentrations were 0.54 microg/L and 0.52 microg/L and post-treatment concentrations were 0.51 microg/L and 0.48 microg/L for placebo and succimer groups, respectively. Because the baseline characteristics in the two groups were balanced and because succimer had little effect on MeHg concentration and no effect on the cognitive or behavioral test scores, the groups were combined in the analysis of MeHg and neurodevelopment. The children's IQ and neurobehavioral performance were tested at age 2, 5 and 7 years. We saw weak, non-significant but consistently positive associations between blood MeHg and IQ test scores in stratified, spline regression and generalized linear model data analyses. The behavioral problem scores were constant or decreased slightly with increasing MeHg concentration. Additional adjustment for PbB levels in multivariable models did not alter the conclusion for MeHg and IQ scores, but did confirm that concurrent PbB was strongly associated with IQ and behavior in TLC children. The effects of MeHg on neurodevelopmental indices did not substantially differ by PbB strata. We conclude that at the present background postnatal MeHg exposure levels of US children, adverse effects on children's IQ and behavior are not detectable. 2009 Elsevier Inc. All rights reserved.

  14. Prolonged morphine treatment alters δ opioid receptor post-internalization trafficking

    PubMed Central

    Ong, E W; Xue, L; Olmstead, M C; Cahill, C M

    2015-01-01

    BACKGROUND AND PURPOSE The δ opioid receptor (DOP receptor) undergoes internalization both constitutively and in response to agonists. Previous work has shown that DOP receptors traffic from intracellular compartments to neuronal cell membranes following prolonged morphine treatment. Here, we examined the effects of prolonged morphine treatment on the post-internalization trafficking of DOP receptors. EXPERIMENTAL APPROACH Using primary cultures of dorsal root ganglia neurons, we measured the co-localization of endogenous DOP receptors with post-endocytic compartments following both prolonged and acute agonist treatments. KEY RESULTS A departure from the constitutive trafficking pathway was observed following acute DOP receptor agonist-induced internalization by deltorphin II. That is, the DOP receptor underwent distinct agonist-induced post-endocytic sorting. Following prolonged morphine treatment, constitutive DOP receptor trafficking was augmented. SNC80 following prolonged morphine treatment also caused non-constitutive DOP receptor agonist-induced post-endocytic sorting. The μ opioid receptor (MOP receptor) agonist DAMGO induced DOP receptor internalization and trafficking following prolonged morphine treatment. Finally, all of the alterations to DOP receptor trafficking induced by both DOP and MOP receptor agonists were inhibited or absent when those agonists were co-administered with a DOP receptor antagonist, SDM-25N. CONCLUSIONS AND IMPLICATIONS The results support the hypothesis that prolonged morphine treatment induces the formation of MOP–DOP receptor interactions and subsequent augmentation of the available cell surface DOP receptors, at least some of which are in the form of a MOP/DOP receptor species. The pharmacology and trafficking of this species appear to be unique compared to those of its individual constituents. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other

  15. Opposite Influence of Perceptual Memory on Initial and Prolonged Perception of Sensory Ambiguity

    PubMed Central

    de Jong, Maartje Cathelijne; Knapen, Tomas; van Ee, Raymond

    2012-01-01

    Observers continually make unconscious inferences about the state of the world based on ambiguous sensory information. This process of perceptual decision-making may be optimized by learning from experience. We investigated the influence of previous perceptual experience on the interpretation of ambiguous visual information. Observers were pre-exposed to a perceptually stabilized sequence of an ambiguous structure-from-motion stimulus by means of intermittent presentation. At the subsequent re-appearance of the same ambiguous stimulus perception was initially biased toward the previously stabilized perceptual interpretation. However, prolonged viewing revealed a bias toward the alternative perceptual interpretation. The prevalence of the alternative percept during ongoing viewing was largely due to increased durations of this percept, as there was no reliable decrease in the durations of the pre-exposed percept. Moreover, the duration of the alternative percept was modulated by the specific characteristics of the pre-exposure, whereas the durations of the pre-exposed percept were not. The increase in duration of the alternative percept was larger when the pre-exposure had lasted longer and was larger after ambiguous pre-exposure than after unambiguous pre-exposure. Using a binocular rivalry stimulus we found analogous perceptual biases, while pre-exposure did not affect eye-bias. We conclude that previously perceived interpretations dominate at the onset of ambiguous sensory information, whereas alternative interpretations dominate prolonged viewing. Thus, at first instance ambiguous information seems to be judged using familiar percepts, while re-evaluation later on allows for alternative interpretations. PMID:22295095

  16. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

    PubMed

    Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

    2016-08-01

    Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

    PubMed Central

    Jonsdottir, Ingibjörg H.; Hägg, Daniel A.; Glise, Kristina; Ekman, Rolf

    2009-01-01

    Background Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. Methodology/Principal Findings Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n = 89) and controls (n = 88) showing a small but significant increase of CRP levels in the patients. Conclusions/Significance MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured. PMID:19888340

  18. Physiologic effects of prolonged conducted electrical weapon discharge in ethanol-intoxicated adults.

    PubMed

    Moscati, Ronald; Ho, Jeffrey D; Dawes, Donald M; Miner, James R

    2010-06-01

    This study examines the physiologic effects of prolonged conducted electrical weapon (CEW) exposure on alcohol-intoxicated adult subjects. Adult volunteers were recruited at a TASER International training conference. All subjects ingested mixed drinks until clinical intoxication or until a minimum breath alcohol level of 0.08 mg/dL was achieved. Blood samples for venous pH, Pco(2), bicarbonate, and lactate were measured in all subjects at baseline, immediately after alcohol ingestion, immediately after exposure to a 15-second TASER X26 discharge (Taser International Inc, Scottsdale, AZ), and 24 hours post-alcohol ingestion. Laboratory values were compared at sampling times using repeated-measure analysis of variance. A focused analysis comparing time points within groups was then performed using paired t tests. Twenty-two subjects were enrolled into the study. There was a decrease in pH and bicarbonate and an increase in lactate after alcohol ingestion. There was a further increase in lactate and drop in pH after CEW exposure. No subject experienced a significant adverse event. All values had returned to baseline levels at 24 hours except lactate, which demonstrated a small but clinically insignificant increase. Prolonged continuous CEW exposure in the setting of acute alcohol intoxication has no clinically significant effect on subjects in terms of markers of metabolic acidosis. The acidosis seen is consistent with what occurs with ethanol intoxication or moderate exertion. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  19. Technologies for Prolonging Cardiac Implantable Electronic Device Longevity.

    PubMed

    Lau, Ernest W

    2017-01-01

    Prolonged longevity of cardiac implantable electronic devices (CIEDs) is needed not only as a passive response to match the prolonging life expectancy of patient recipients, but will also actively prolong their life expectancy by avoiding/deferring the risks (and costs) associated with device replacement. CIEDs are still exclusively powered by nonrechargeable primary batteries, and energy exhaustion is the dominant and an inevitable cause of device replacement. The longevity of a CIED is thus determined by the attrition rate of its finite energy reserve. The energy available from a battery depends on its capacity (total amount of electric charge), chemistry (anode, cathode, and electrolyte), and internal architecture (stacked plate, folded plate, and spiral wound). The energy uses of a CIED vary and include a background current for running electronic circuitry, periodic radiofrequency telemetry, high-voltage capacitor reformation, constant ventricular pacing, and sporadic shocks for the cardiac resynchronization therapy defibrillators. The energy use by a CIED is primarily determined by the patient recipient's clinical needs, but the energy stored in the device battery is entirely under the manufacturer's control. A larger battery capacity generally results in a longer-lasting device, but improved battery chemistry and architecture may allow more space-efficient designs. Armed with the necessary technical knowledge, healthcare professionals and purchasers will be empowered to make judicious selection on device models and maximize the utilization of all their energy-saving features, to prolong device longevity for the benefits of their patients and healthcare systems. © 2016 Wiley Periodicals, Inc.

  20. Vestibulo-Cervico-Ocular Responses and Tracking Eye Movements after Prolonged Exposure to Microgravity

    NASA Technical Reports Server (NTRS)

    Kornilova, L. N.; Naumov, I. A.; Azarov, K. A.; Sagalovitch, S. V.; Reschke, Millard F.; Kozlovskaya, I. B.

    2007-01-01

    The vestibular function and tracking eye movements were investigated in 12 Russian crew members of ISS missions on days 1(2), 4(5-6), and 8(9-10) after prolonged exposure to microgravity (126 to 195 days). The spontaneous oculomotor activity, static torsional otolith-cervico-ocular reflex, dynamic vestibulo-cervico-ocular responses, vestibular reactivity, tracking eye movements, and gaze-holding were studied using videooculography (VOG) and electrooculography (EOG) for parallel eye movement recording. On post-flight days 1-2 (R+1-2) some cosmonauts demonstrated: - an increased spontaneous oculomotor activity (floating eye movements, spontaneous nystagmus of the typical and atypical form, square wave jerks, gaze nystagmus) with the head held in the vertical position; - suppressed otolith function (absent or reduced by one half amplitude of torsional compensatory eye counter-rolling) with the head inclined statically right- or leftward by 300; - increased vestibular reactivity (lowered threshold and increased intensity of the vestibular nystagmus) during head turns around the longitudinal body axis at 0.125 Hz; - a significant change in the accuracy, velocity, and temporal characteristics of the eye tracking. The pattern, depth, dynamics, and velocity of the vestibular function and tracking eye movements recovery varied with individual participants in the investigation. However, there were also regular responses during readaptation to the normal gravity: - suppression of the otolith function was typically accompanied by an exaggerated vestibular reactivity; - the structure of visual tracking (the accuracy of fixational eye rotations, smooth tracking, and gaze-holding) was disturbed (the appearance of correcting saccades, the transition of smooth tracking to saccadic tracking) only in those cosmonauts who, in parallel to an increased reactivity of the vestibular input, also had central changes in the oculomotor system (spontaneous nystagmus, gaze nystagmus).

  1. Prolonged exposure to 1,25(OH)2D3 and high ionized calcium induces FGF-23 production in intestinal epithelium-like Caco-2 monolayer: A local negative feedback for preventing excessive calcium transport.

    PubMed

    Rodrat, Mayuree; Wongdee, Kannikar; Panupinthu, Nattapon; Thongbunchoo, Jirawan; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2018-02-15

    Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH) 2 D 3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH) 2 D 3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH) 2 D 3 . FGF-23 exposure completely abolished the 1,25(OH) 2 D 3 -enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH) 2 D 3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial.

    PubMed

    Flanagan, Julianne C; Sippel, Lauren M; Wahlquist, Amy; Moran-Santa Maria, Megan M; Back, Sudie E

    2018-03-01

    Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition for which Prolonged Exposure (PE) therapy is highly efficacious. However, for some individuals, premature dropout and residual PTSD symptoms remain obstacles. The neuropeptide oxytocin is a promising candidate to enhance PE due to its ability to enhance 1) prosocial cognition and behavior, which are theorized to promote positive working alliance, and 2) extinction learning, which is the central mechanism of action underlying successful PE treatment. Despite a robust theoretical rationale, no studies to date have combined evidence-based psychotherapy for PTSD with oxytocin. This randomized, placebo-controlled, double-blind pilot trial examined the feasibility, safety, and preliminary efficacy of augmenting PE with oxytocin. Participants were 17 individuals with diverse index traumas. Participants self-administered intranasal oxytocin (40 IU) or matching placebo 45 min prior to each weekly PE therapy session. One adverse event occurred in the placebo group and three individuals dropped out (17.6%; 2 oxytocin group and 1 placebo group). The oxytocin group demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores, although these differences did not reach statistical significance. Although preliminary, the findings support the feasibility of oxytocin combined with PE. Adequately powered studies are necessary to determine whether oxytocin enhances PE treatment outcomes and to examine potential mechanisms, such as accelerating extinction learning, enhancing early response, and preventing premature dropout. NCT03238924. Copyright © 2017. Published by Elsevier Ltd.

  3. Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Lei; Zhuang, Jianguo; Zang, Na

    Prenatal nicotinic exposure (PNE) prolongs bronchopulmonary C-fiber (PCF)-mediated apneic response to intra-atrial bolus injection of capsaicin in rat pups. The relevant mechanisms remain unclear. Pulmonary substance P and adenosine and their receptors (neurokinin-A receptor, NK1R and ADA{sub 1} receptor, ADA{sub 1}R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) expressed on PCFs are critical for PCF sensitization and/or activation. Here, we compared substance P and adenosine in BALF and NK1R, ADA{sub 1}R, and TRPV1 expression in the nodose/jugular (N/J) ganglia (vagal pulmonary C-neurons retrogradely labeled) between Ctrl and PNE pups. We found that PNE failed to changemore » BALF substance P and adenosine content, but significantly upregulated both mRNA and protein TRPV1 and NK1R in the N/J ganglia and only NK1R mRNA in pulmonary C-neurons. To define the role of NK1R in the PNE-induced PCF sensitization, the apneic response to capsaicin (i.v.) without or with pretreatment of SR140333 (a peripheral and selective NK1R antagonist) was compared and the prolonged apnea by PNE significantly shortened by SR140333. To clarify if the PNE-evoked responses depended on action of nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, mecamylamine or methyllycaconitine (a general nAChR or a selective α7nAChR antagonist) was administrated via another mini-pump over the PNE period. Mecamylamine or methyllycaconitine eliminated the PNE-evoked mRNA and protein responses. Our data suggest that PNE is able to elevate PCF NK1R expression via activation of nAChRs, especially α7nAChR, which likely contributes to sensitize PCFs and prolong the PCF-mediated apneic response to capsaicin. - Highlights: • PNE upregulated NK1R and TRPV1 gene and protein expression in the N/J ganglia. • PNE only elevated NK1R mRNA in vagal pulmonary C-neurons. • Blockage of peripheral NK1R reduced the PNE-induced PCF sensitization. • PNE induced gene and

  4. Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

    PubMed Central

    Penagini, Roberto; Sweis, Rami; Mauro, Aurelio; Domingues, Gerson; Vales, Andres; Sifrim, Daniel

    2015-01-01

    Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients (P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management. PMID:25843078

  5. Evaluation of benzodiazepines and zolpidem in nails and their stability after prolonged exposure to chlorinated water.

    PubMed

    Moretti, Matteo; Andrello, Luisa; Visonà, Silvia; Vignali, Claudia; Groppi, Angelo; Freni, Francesca; Osculati, Antonio; Tajana, Luca; Morini, Luca

    2018-04-15

    The study aims the development and validation of a LC-MS/MS method for the identification and quantification of benzodiazepines and zolpidem in nails as alternative keratinized matrix to hair in long-term monitoring of anxiolytic and hypnotic drugs. Both fingernail and toenail samples (1-2 mm) were collected by clipping the excess overhang of the nail from volunteers and from postmortem cases. They were washed twice with organic solvents, dried under nitrogen stream, pulverized, immersed in a methanol solution (internal standard: diazepam-D5) and sonicated up to two hours. The solution was then direct injected in the LC-MS/MS system. Mass spectrometry was set in MRM mode, selecting two transitions for each substance. 32 analytes among benzodiazepines, metabolites and hypnotics were included in the list. The method fulfilled the internationally required criteria for validation. Limits of detection ranged from 0.03 pg/mg (zolpidem) to 13.1 pg/mg (bromazepam). 9 subjects under therapy were positive at 7 different benzodiazepines and/or metabolites (lorazepam, desalkylflurazepam, bromazepam, diazepam, alprazolam, lormetazepam and prazepam), while 5 molecules were measured in 4 postmortem cases (diazepam, desmethyldiazepam, delorazepam, 7-aminoclonazepam and zolpidem). In vitro experiments on eight authentic samples suggested that benzodiazepines in nails are influenced by the prolonged exposure to chlorinated water. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Prolonged Exposure Therapy With Veterans and Active Duty Personnel Diagnosed With PTSD and Traumatic Brain Injury.

    PubMed

    Wolf, Gregory K; Kretzmer, Tracy; Crawford, Eric; Thors, Christina; Wagner, H Ryan; Strom, Thad Q; Eftekhari, Afsoon; Klenk, Megan; Hayward, Laura; Vanderploeg, Rodney D

    2015-08-01

    The present study used archival clinical data to analyze the delivery and effectiveness of prolonged exposure (PE) and ancillary services for posttraumatic stress disorder (PTSD) among Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans (N = 69) with histories of mild to severe traumatic brain injury (TBI). Data from standard clinical assessments of veterans and active duty personnel treated in both inpatient and outpatient programs at 2 Department of Veteran Affairs medical centers were examined. Symptoms were assessed with self-report measures of PTSD (PTSD Checklist) and depression (Beck Depression Inventory-II) before and throughout therapy. Mixed linear models were utilized to determine the slope of reported symptoms throughout treatment, and the effects associated with fixed factors such as site, treatment setting (residential vs. outpatient), and TBI severity were examined. Results demonstrated significant decreases in PTSD, B = -3.00, 95% CI [-3.22, -2.78]; t(210) = -13.5; p < .001, and in depressive symptoms, B = -1.46, 95% CI [-1.64, -1.28]; t(192) = -8.32; p < .001. The effects of PE treatment did not differ by clinical setting and participants with moderate to severe injuries reported more rapid gains than those with a history of mild TBI. The results provide evidence that PE may well be effective for veterans with PTSD and TBI. Copyright © 2015 International Society for Traumatic Stress Studies.

  7. Defining futile life-prolonging treatments through Neo-Socratic Dialogue.

    PubMed

    Aizawa, Kuniko; Asai, Atsushi; Bito, Seiji

    2013-12-09

    In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: "What is a life-prolonging treatment?" A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient's lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the objective of treatment, its effects

  8. [Secondary traumatization/trauma among employees in palliative care units--the products of prolonged repeated exposure to suffering and death].

    PubMed

    Samson, Tali; Shvartzman, Pesach

    2012-11-01

    The palliative care philosophy accepts the dying process as a natural phase in the life cycle and provides quality end of life care for terminal patients and their family members. Prolonged exposure to the physical symptoms and pain, as well as the psychological, spiritual, and existential suffering of the dying patient, may be fertile ground for the development of post-traumatic stress symptoms among palliative care teams. Work-related positive outcomes (such as compassion, satisfaction and meaning) and work-related negative outcomes (such as compassion fatigue, secondary traumatization and burnout) can exist side by side, and the unique balance between them will determine the quality of life of the worker. This review presents the current knowledge about the prevalence and causes of work-related stress outcomes among palliative care teams and measurement tools that are available. The literature review discusses secondary traumatization in palliative care teams and relevant messages for the development of treatment options, burnout prevention programs and support interventions for professionals who lead the care for terminal patients in Israel.

  9. Association of Radon Background and Total Background Ionizing Radiation with Alzheimer's Disease Deaths in U.S. States.

    PubMed

    Lehrer, Steven; Rheinstein, Peter H; Rosenzweig, Kenneth E

    2017-01-01

    Exposure of the brain to ionizing radiation might promote the development of Alzheimer's disease (AD). Analysis of AD death rates versus radon background radiation and total background radiation in U.S. states. Total background, radon background, cosmic and terrestrial background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States and Report No. 160 - Ionizing Radiation Exposure of the Population of the United States. 2013 AD death rates by U.S. state are from the Alzheimer's Association. Radon background ionizing radiation was significantly correlated with AD death rate in 50 states and the District of Columbia (r = 0.467, p = 0.001). Total background ionizing radiation was also significantly correlated with AD death rate in 50 states and the District of Columbia (r = 0.452, p = 0.001). Multivariate linear regression weighted by state population demonstrated that AD death rate was significantly correlated with radon background (β= 0.169, p < 0.001), age (β= 0.231, p < 0.001), hypertension (β= 0.155, p < 0.001), and diabetes (β= 0.353, p < 0.001). Our findings, like other studies, suggest that ionizing radiation is a risk factor for AD. Intranasal inhalation of radon gas could subject the rhinencephalon and hippocampus to damaging radiation that initiates AD. The damage would accumulate over time, causing age to be a powerful risk factor.

  10. Cooperation between Strain-Specific and Broadly Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the Broadly Neutralizing Epitope

    PubMed Central

    Anthony, Colin; York, Talita; Bekker, Valerie; Matten, David; Selhorst, Philippe; Ferreria, Roux-Cil; Garrett, Nigel J.; Karim, Salim S. Abdool; Morris, Lynn; Wood, Natasha T.; Moore, Penny L.

    2017-01-01

    ABSTRACT V3-glycan-targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep-sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan-directed bNAbs compared to overlapping early strain-specific neutralizing antibody (ssNAb) responses to the V3/C3 region in donor CAP177. Escape from the ssNAb response occurred rapidly via an N334-to-N332 glycan switch, which took just 7.5 weeks to reach >50% frequency. In contrast, escape from the bNAbs was mediated via multiple pathways and took longer, with escape first occurring through an increase in V1 loop length, which took 46 weeks to reach 50% frequency, followed by an N332-to-N334 reversion, which took 66 weeks. Importantly, bNAb escape was incomplete, with contemporaneous neutralization observed up to 3 years postinfection. Both the ssNAb response and the bNAb response were modulated by the presence/absence of the N332 glycan, indicating an overlap between the two epitopes. Thus, selective pressure by ssNAbs to maintain the N332 glycan may have constrained the bNAb escape pathway. This slower and incomplete viral escape resulted in prolonged exposure of the bNAb epitope, which may in turn have aided the maturation of the bNAb lineage. IMPORTANCE The development of an HIV-1 vaccine is of paramount importance, and broadly neutralizing antibodies are likely to be a key component of a protective vaccine. The V3-glycan-targeting bNAb responses are among the most promising vaccine targets, as they are commonly elicited during infection. Understanding the interplay between viral evolution and the development of these antibodies provides insights that may guide immunogen design. Our work contrasted the dynamics of the early strain-specific antibodies and the later broadly neutralizing

  11. Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment.

    PubMed

    Nystedt, Astrid; Hildingsson, Ingegerd

    2014-07-16

    Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women's experiences of prolonged and normal labour. Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic and obstetric background, birth outcome and women's feelings and experiences of birth. The prevalence of prolonged labour, as defined by a documented ICD-code and inspection of partogram was calculated. Four groups were identified; women with prolonged labour as identified by documented ICD-codes or by partogram inspection but no ICD-code; women with normal labour augmented with oxytocin or not. Every fifth woman experienced a prolonged labour. The prevalence with the documented ICD-code was (13%) and without ICD-code but positive partogram was (8%). Seven percent of women with prolonged labour were not treated with oxytocin. Approximately one in three women (28%) received oxytocin augmentation despite having no evidence of prolonged labour. The length of labour differed between the four groups of women, from 7 to 23 hours.Women with a prolonged labour had a negative birth experience more often (13%) than did women who had a normal labour (3%) (P <0.00). The factors that contributed most strongly to a negative birth experience in women with prolonged labour were emergency Caesarean section (OR 9.0, 95% CI 1.2-3.0) and to strongly agree with the following statement 'My birth experience made me decide not to have any more children' (OR 41.3, 95% CI 4.9-349.6). The factors that contributed most strongly to a negative birth experience in women with normal labour were less agreement with the statement 'It was exiting to give birth' (OR 0.13, 95% CI 0.34-0.5). There is need for increased clinical skill in

  12. QTc prolongation after brain surgery.

    PubMed

    Capparelli, Federico J; Abello, Mauricio; Patricio Maskin, L; Arista, Eugenia; Hlavnicka, Alejandro; Diaz, Maria Fernanda; Varela, Daniel; Wainsztein, Nestor A

    2013-03-01

    Abnormalities observed in the electrocardiogram (ECG) after acute central nervous system (CNS) events have been reported. Our objective was to assess the incidence of heart rate-corrected QT interval (QTc) prolongation in patients admitted to the intensive care unit (ICU) after brain surgery. Admission standard 12-lead ECGs were analyzed blinded to patient data. The QT interval was measured and Bazzett's formula was used to obtain QTc. Prolonged QTc was defined as ≧450 ms. We included 114 patients in the study. The mean age was 49±17 years. Brain neoplasm was the surgical indication in 90% of the patients. The mean QTc was 470±42 ms. Prolonged QTc was found in 71% patients. The heart rate-corrected QT interval was between 450 ms and 500 ms in 52% and >500 ms in 19% of the patients. The heart rate and concentration of serum glucose were higher in the prolonged QTc group. Only 7·5% of all patients had hypokalemia (≤3 mEq/l). In the prolonged QTc group 9·2% had hypokalemia compared to 3·2% in normal QTc patients (P = 0·406). There were no significant associations between categories of QTc and the serum levels of creatinine, magnesium, calcium, sodium, or pH. Phenytoin and metoclopramide were not frequently used in patients with prolonged QTc. This study supports our hypothesis that prolonged QTc is frequently observed after a brain surgery. Hypokalemia, hypocalcaemia, and drugs such as metoclopramide or phenytoin could not explain the high incidence of prolonged QTc. Brain injury during a surgical procedure may be one of the primary causes of QTc prolongation after neurosurgery.

  13. Web-PE: Internet-Delivered Prolonged Exposure Therapy for PTSD

    DTIC Science & Technology

    2015-10-01

    order to meet the growing demand for effective and efficient treatment for posttraumatic stress disorder ( PTSD ) in a timely manner. Web-treatments...posttraumatic stress disorder ( PTSD ) in a timely manner. Effective EBTs for PTSD are available, but barriers to accessing care can deter military...Exposure, combat, psychological treatment, military, psychotherapy, trauma, posttraumatic stress , posttraumatic stress disorder 16. SECURITY

  14. Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

    NASA Technical Reports Server (NTRS)

    Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

    1998-01-01

    Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

  15. Assessment of impact of urbanisation on background radiation exposure and human health risk estimation in Kuala Lumpur, Malaysia.

    PubMed

    Sanusi, M S M; Ramli, A T; Hassan, W M S W; Lee, M H; Izham, A; Said, M N; Wagiran, H; Heryanshah, A

    2017-07-01

    Kuala Lumpur has been undergoing rapid urbanisation process, mainly in infrastructure development. The opening of new township and residential in former tin mining areas, particularly in the heavy mineral- or tin-bearing alluvial soil in Kuala Lumpur, is a contentious subject in land-use regulation. Construction practices, i.e. reclamation and dredging in these areas are potential to enhance the radioactivity levels of soil and subsequently, increase the existing background gamma radiation levels. This situation is worsened with the utilisation of tin tailings as construction materials apart from unavoidable soil pollutions due to naturally occurring radioactive materials in construction materials, e.g. granitic aggregate, cement and red clay brick. This study was conducted to assess the urbanisation impacts on background gamma radiation in Kuala Lumpur. The study found that the mean value of measured dose rate was 251±6nGyh -1 (156-392nGyh -1 ) and 4 times higher than the world average value. High radioactivity levels of 238 U (95±12Bqkg -1 ), 232 Th (191±23Bqkg -1 ,) and 40 K (727±130Bqkg -1 ) in soil were identified as the major source of high radiation exposure. Based on statistical ANOVA, t-test, and analyses of cumulative probability distribution, this study has statistically verified the dose enhancements in the background radiation. The effective dose was estimated to be 0.31±0.01mSvy -1 per man. The recommended ICRP reference level (1-20mSvy -1 ) is applicable to the involved existing exposure situation in this study. The estimated effective dose in this study is lower than the ICRP reference level and too low to cause deterministic radiation effects. Nevertheless based on estimations of lifetime radiation exposure risks, this study found that there was small probability for individual in Kuala Lumpur being diagnosed with cancer and dying of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (–)-epigallocatechin-3-gallate

    PubMed Central

    He, Yan; Cui, Jiankun; Lee, James C-M; Ding, Shinghua; Chalimoniuk, Malgorzata; Simonyi, Agnes; Sun, Albert Y; Gu, Zezong; Weisman∥, Gary A; Gibson Wood, W; Sun, Grace Y

    2011-01-01

    Excessive production of Aβ (amyloid β-peptide) has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease). Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species) in neurons through an NMDA (N-methyl-d-aspartate)-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid) release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III)-tetrakis(4-benzoic acid)-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pre-treatment of neurons with EGCG [(−)-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD. PMID:21434871

  17. Bronchopulmonary C-fibers' IL1RI contributes to the prolonged apneic response to intra-atrial injection of capsaicin by prenatal nicotinic exposure in rat pups

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Lei; Zhuang, Jianguo; Xu, Fadi, E-mail: fxu@

    Prenatal nicotinic exposure (PNE) as a SIDS model reportedly sensitizes bronchopulmonary C-fibers (PCFs), contributing to the prolonged PCF-mediated apnea in rat pups, but the relevant mechanisms are not fully understood. Pulmonary IL-1β upregulated by cigarette smoke is known to stimulate or sensitize PCFs acting via IL-1 type I receptor (IL1RI) and inhibit inspiration frequency. Because of its upregulation observed in SIDS victims, we hypothesized that PNE increased pulmonary IL-1β release and IL1RI expression in pulmonary C-neurons via action on α7 nicotinic acetylcholine receptors (α7nAChR) to induce the prolonged PCF-mediated apnea. IL-1β in BALF and IL1RI in the nodose/jugular (N/J) ganglionmore » and vagal pulmonary C-neurons retrogradely-traced were compared between Ctrl (saline) and PNE pups and among the vehicle-treated Ctrl and PNE and methyllycaconitine (a selective α7nAChR antagonist)-treated PNE pups. The effect of IL-1RI blockade (IL-1Ra) on the PCF-mediated apnea was also compared between Ctrl and PNE pups. PNE significantly elevated IL-1β in BALF and upregulated IL1RI gene and protein expression in N/J ganglia and gene in vagal pulmonary C-neurons. All of these responses were eliminated by pretreatment with blockade of α7nAChR. In addition, the prolonged PCF-mediated apnea in PNE pups was significantly shortened by right atrial bolus injection of IL-1Ra. We conclude that PNE enhances pulmonary IL-1β release and PCF IL1RI expression acting via α7nAChR in contributing to sensitization of PCFs and prolongation of the PCF-mediated apneic response. - Highlights: • PNE increased pulmonary IL-1β release and IL1R1 expression in the N/J ganglia. • PNE elevated IL1R1 mRNA in vagal pulmonary C-neurons. • Blockage of peripheral IL1R1 reduced the PNE-induced PCF sensitization. • PNE induced the changes in IL-1β and IL1R1 dependent on action of α7nAChR.« less

  18. Prolonged fatigue in Ukraine and the United States: Prevalence and risk factors

    PubMed Central

    Friedberg, Fred; Tintle, Nathan; Clark, Jake; Bromet, Evelyn J.

    2015-01-01

    Background Prolonged, severe, unalleviated fatigue may be disabling whether it occurs on its own or in conjunction with medical or psychiatric conditions. This paper compares the prevalence and correlates of prolonged fatigue in general population samples in Ukraine versus the U.S. Methods Population surveys were conducted in 2002 in both Ukraine (Ukraine World Mental Health [WMH] Survey) and the U.S. (National Comorbidity Survey-Replication; NCS-R). Both surveys administered the Composite International Diagnostic Interview (CIDI 3.0), which contained modules assessing: neurasthenia (prolonged fatigue); mood, anxiety, and alcohol/drug use disorders; chronic medical conditions; and demographic characteristics. Multivariable logistic regression was used to examine risk factors in each country. Results The lifetime prevalence of prolonged fatigue was higher in Ukraine (5.2%) than the U.S. (3.7%). In both countries, one-fifth of individuals with prolonged fatigue had no medical or DSM-IV psychiatric condition. Also in both settings, fatigue was significantly associated with sociodemographic characteristics (being female, not working, and married before) as well as early onset and adult episodes of mood/anxiety disorder. Fatigue prevalence in Ukraine increased with age, but decreased in the U.S. at age 70. Unique risk factors for fatigue in Ukraine included lower socio-economic status, Ukrainian vs Russian ethnicity, and cardiovascular disease. Unique risk factors in the U.S. were parental depression/anxiety, adult episodes of alcohol/drugs, pain conditions, and other health problems. Conclusions The lifetime prevalence of prolonged fatigue in Ukraine was 40% higher than that found in U.S. data. In addition, fatigue prevalence increased sharply with age in Ukraine perhaps due to limited social and medical resources and greater comorbidity. PMID:26807341

  19. Effects of incomplete residential histories on studies of environmental exposure with application to childhood leukaemia and background radiation.

    PubMed

    Nikkilä, Atte; Kendall, Gerald; Raitanen, Jani; Spycher, Ben; Lohi, Olli; Auvinen, Anssi

    2018-06-22

    When evaluating environmental exposures, residential exposures are often most relevant. In most countries, it is impossible to establish full residential histories. In recent publications, childhood leukaemia and background radiation have been studied with and without full residential histories. This paper investigates the consequences of lacking such full data. Data from a nationwide Finnish Case-Control study of Childhood Leukaemia and gamma rays were analysed. This included 1093 children diagnosed with leukaemia in Finland in 1990-2011. Each case was matched by gender and year of birth to three controls. Full residential histories were available. The dose estimates were based on outdoor background radiation measurements. The indoor dose rates were obtained with a dwelling type specific conversion coefficient and the individual time-weighted mean red bone marrow dose rates were calculated using age-specific indoor occupancy and the age and gender of the child. Radiation from Chernobyl fallout was included and a 2-year latency period assumed. The median separation between successive dwellings was 3.4 km and median difference in red bone marrow dose 2.9 nSv/h. The Pearson correlation between the indoor red bone marrow dose rates of successive dwellings was 0.62 (95% CI 0.60, 0.64). The odds ratio for a 10 nSv/h increase in dose rate with full residential histories was 1.01 (95% CI 0.97, 1.05). Similar odds ratios were calculated with dose rates based on only the first dwelling (1.02, 95% CI 0.99, 1.05) and only the last dwelling (1.00, 95% CI 0.98, 1.03) and for subjects who had lived only in a single dwelling (1.05, 95% CI 0.98, 1.10). Knowledge of full residential histories would always be the option of choice. However, due to the strong correlation between exposure estimates in successive dwellings and the uncertainty about the most relevant exposure period, estimation of overall exposure level from a single address is also informative. Error in dose

  20. The "PE coach" smartphone application: an innovative approach to improving implementation, fidelity, and homework adherence during prolonged exposure.

    PubMed

    Reger, Greg M; Hoffman, Julia; Riggs, David; Rothbaum, Barbara O; Ruzek, Josef; Holloway, Kevin M; Kuhn, Eric

    2013-08-01

    Prolonged exposure (PE) is an empirically supported treatment that is being disseminated broadly to providers in the Department of Veterans Affairs and Department of Defense. Innovative methods are needed to support the implementation, dissemination, and patient and provider adherence to PE. The PE Coach is a smartphone application (app) designed to mitigate barriers to PE implementation. PE Coach is installed on the patient's phone and includes a range of capabilities for use during the PE session and after each session to support the treatment. Functions include the ability to audio record treatment sessions onto the patient's device, to construct the in vivo hierarchy on the device, to record completed homework exercises, to review homework adherence, and to track symptom severity over time. The app also allows sessions and homework to be scheduled directly in the app, populating the device calendar with patient reminder notifications. In the final session, a visual display of symptom improvement and habituation to items on the in vivo hierarchy is presented. These capabilities may significantly improve convenience, provider implementation and adherence, and patient compliance with treatment. Future research is needed to test whether PE Coach is useful and effective. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  1. Prolonged environment-induced hyperthermia alters autophagy in oxidative skeletal muscle in Sus scrofa.

    PubMed

    Ganesan, Shanthi; Brownstein, Alexandra J; Pearce, Sarah C; Hudson, Matthew B; Gabler, Nicolas K; Baumgard, Lance H; Rhoads, Robert P; Selsby, Joshua T

    2018-05-01

    Prolonged heat stress represents a continuing threat to human health and agricultural production. Despite the broad, negative impact of prolonged hyperthermia little is known about underlying pathological mechanisms leading to negative health outcomes, which has limited the development of etiological interventions and left clinicians and producers with only cooling and rehydration strategies. The purpose of this investigation was to determine the extent to which prolonged environment-induced hyperthermia altered autophagy in oxidative skeletal muscle in a large animal model, serving the dual purpose of accurately modeling human physiology as well as agricultural production. We hypothesized that prolonged hyperthermia would induce autophagy in skeletal muscle, independent of the accompanying caloric restriction. To test this hypothesis pigs were treated as follows: thermoneutral (20 °C), heat stress (35 °C), or were held under thermoneutral conditions but pair-fed to the heat stress group for seven days. Upon euthanasia the red portion of the semitendinosus was collected. We found that prolonged hyperthermic exposure increased oxidative stress without a corresponding change in antioxidant enzyme activities. Hyperthermia prevented initiation of autophagy despite increased markers of nucleation, elongation and autophagosome formation. However, p62 relative protein abundance, which is inversely correlated with autophagic degradation, was strongly increased suggesting suppressed degradation of autophagosomes. Markers of mitophagy and mitochondrial abundance were largely similar between groups. These data indicate that faulty autophagy plays a key role in hyperthermic muscle dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Paternal work stress and prolonged time to pregnancy.

    PubMed

    Lee, Mi-Sun; Paek, Domyung; Eum, Ki-Do; Siegrist, Johannes; Li, Jian; Lee, Hye-Eun; Cho, Sung-Il

    2009-01-01

    The aim of this study was to explore an association between psychosocial stress at work in married men and their spouses' prolonged time to pregnancy (TTP). All married male workers of a large Korean petrochemical enterprise and their wives fulfilling the selection criteria were included. Main selection criteria were lack of use of contraceptives and experienced pregnancy in recent past. Data were available from 322 couples. Psychosocial stress at work was measured by the effort-reward imbalance questionnaire. Prolonged TTP was measured by the "TTP questionnaire". After adjustment for confounding effects of demographic and life-style characteristics and benzene exposure, delayed TTP, defined by frequency of first-cycle pregnancy, was associated with one standard deviation (SD) increase of the effort-reward ratio in the chronically stressed group of married men (OR = 0.47; 95% CI = 0.22-0.99) in logistic regression analysis. A similar, but somewhat weaker effect, was found for the overall group (OR = 0.67; 95% CI = 0.47-0.94). Paternal stress at work, as measured by effort-reward imbalance, seemed to be associated with a decreased number of conceptions in the first menstrual cycle.

  3. Recovery of Breathing and Forelimb Function after Prolonged Exposure to Repetitive Acute Intermittent Hypoxia

    DTIC Science & Technology

    2017-03-01

    breathing capacity (Aim 1) and forelimb function (Aim 2), without systemic hypertension or hippocampal pathology (Aim 3). SPECIFIC AIMS Aim 1 (Florida...benefits. On the other hand, there was no evidence for pathology ( hypertension or hippocampal pathology). We were not able to perform time-series... hypertension or hippocampal (CA1) pathology. However, we did see striking (and surprising) preliminary evidence that prolonged rAIH: 1) reduced volume of the

  4. The Association between Job-Related Psychosocial Factors and Prolonged Fatigue among Industrial Employees in Taiwan

    PubMed Central

    Tang, Feng-Cheng; Li, Ren-Hau; Huang, Shu-Ling

    2016-01-01

    Background and Objectives Prolonged fatigue is common among employees, but the relationship between prolonged fatigue and job-related psychosocial factors is seldom studied. This study aimed (1) to assess the individual relations of physical condition, psychological condition, and job-related psychosocial factors to prolonged fatigue among employees, and (2) to clarify the associations between job-related psychosocial factors and prolonged fatigue using hierarchical regression when demographic characteristics, physical condition, and psychological condition were controlled. Methods A cross-sectional study was employed. A questionnaire was used to obtain information pertaining to demographic characteristics, physical condition (perceived physical health and exercise routine), psychological condition (perceived mental health and psychological distress), job-related psychosocial factors (job demand, job control, and workplace social support), and prolonged fatigue. Results A total of 3,109 employees were recruited. Using multiple regression with controlled demographic characteristics, psychological condition explained 52.0% of the variance in prolonged fatigue. Physical condition and job-related psychosocial factors had an adjusted R2 of 0.370 and 0.251, respectively. Hierarchical multiple regression revealed that, among job-related psychosocial factors, job demand and job control showed significant associations with fatigue. Conclusion Our findings highlight the role of job demand and job control, in addition to the role of perceived physical health, perceived mental health, and psychological distress, in workers’ prolonged fatigue. However, more research is required to verify the causation among all the variables. PMID:26930064

  5. Translating QT interval prolongation from conscious dogs to humans.

    PubMed

    Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

    2017-02-01

    In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

  6. Experience with prolonged induced hypothermia in severe head injury

    PubMed Central

    Bernard, Stephen A; MacC Jones, Bruce; Buist, Michael

    1999-01-01

    Background: Recent prospective controlled trials of induced moderate hypothermia (32⌓34°C) for relatively short periods (24⌓48 h) in patients with severe head injury have suggested improvement in intracranial pressure control and outcome. It is possible that increased benefit might be achieved if hypothermia was maintained for more periods longer than 48 h, but there is little in the literature on the effects of prolonged moderate hypothermia in adults with severe head injury. We used moderate induced hypothermia (30⌓33°C) in 43 patients with severe head injury for prolonged periods (mean 8 days, range 2⌓19 days). Results: Although nosocomial pneumonia (defined in this study as both new chest radiograph changes and culture of a respiratory pathogen from tracheal aspirate) was quite common (45%), death from sepsis was rare (5%). Other findings included hypokalaemia on induction of hypothermia and a decreasing total white cell and platelet count over 10 days. There were no major cardiac arrhythmias. There was a satisfactory neurological outcome in 20 out of 43 patients (47%). Conclusion: Moderate hypothermia may be induced for more prolonged periods, and is a relatively safe and feasible therapeutic option in the treatment of selected patients with severe traumatic brain injury. Thus, further prospective controlled trials using induced hypothermia for longer periods than 48 h are warranted. PMID:11056742

  7. Identifying the translational gap in the evaluation of drug-induced QTc interval prolongation

    PubMed Central

    Chain, Anne SY; Dubois, Vincent FS; Danhof, Meindert; Sturkenboom, Miriam CJM; Della Pasqua, Oscar

    2013-01-01

    Aims Given the similarities in QTc response between dogs and humans, dogs are used in pre-clinical cardiovascular safety studies. The objective of our investigation was to characterize the PKPD relationships and identify translational gaps across species following the administration of three compounds known to cause QTc interval prolongation, namely cisapride, d, l-sotalol and moxifloxacin. Methods Pharmacokinetic and pharmacodynamic data from experiments in conscious dogs and clinical trials were included in this analysis. First, pharmacokinetic modelling and deconvolution methods were applied to derive drug concentrations at the time of each QT measurement. A Bayesian PKPD model was then used to describe QT prolongation, allowing discrimination of drug-specific effects from other physiological factors known to alter QT interval duration. A threshold of ≥10 ms was used to explore the probability of prolongation after drug administration. Results A linear relationship was found to best describe the pro-arrhythmic effects of cisapride, d,l-sotalol and moxifloxacin both in dogs and in humans. The drug-specific parameter (slope) in dogs was statistically significantly different from humans. Despite such differences, our results show that the probability of QTc prolongation ≥10 ms in dogs nears 100% for all three compounds at the therapeutic exposure range in humans. Conclusions Our findings indicate that the slope of PKPD relationship in conscious dogs may be used as the basis for the prediction of drug-induced QTc prolongation in humans. Furthermore, the risk of QTc prolongation can be expressed in terms of the probability associated with an increase ≥10 ms, allowing direct inferences about the clinical relevance of the pro-arrhythmic potential of a molecule. PMID:23351036

  8. Distinct effects of brief and prolonged adaptation on orientation tuning in primary visual cortex

    PubMed Central

    Patterson, Carlyn A.; Wissig, Stephanie C.; Kohn, Adam

    2013-01-01

    Recent stimulus history–adaptation–alters neuronal responses and perception. Previous electrophysiological and perceptual studies suggest that prolonged adaptation strengthens and makes more persistent the effects seen after briefer exposures. However, no systematic comparison has been made between the effects of adaptation lasting hundreds of milliseconds, which might arise during a single fixation, and the more prolonged adaptation typically used in imaging and perceptual studies. Here we determine how 0.4 s, 4 s, and 40 s of adaptation alters orientation tuning in primary visual cortex of anesthetized macaque monkeys, and how quickly responses recover after adapter offset. We measured responses to small (1.3 deg) and large (7.4 deg) gratings because previous work has shown that adaptation effects can depend on stimulus size. Adaptation with small gratings reduced responsivity and caused tuning to shift away from the adapter. These effects strengthened with more prolonged adaptation. For responses to large gratings, brief and prolonged adaptation produced indistinguishable effects on responsivity but caused opposite shifts in tuning preference. Recovery from adaptation was notably slower after prolonged adaptation, even when this did not induce stronger effects. We show that our results can be explained by an adaptation-induced weakening of surround suppression, the dynamics of this suppression, and differential effects of brief and prolonged adaptation across response epochs. Our findings show that effects do not simply scale with adaptation duration, and suggest that distinct strategies exist for adjusting to moment-to-moment fluctuations in input and to more persistent visual stimuli. PMID:23303933

  9. Effect of Prolonged Exposure Therapy Delivered Over 2 Weeks vs 8 Weeks vs Present-Centered Therapy on PTSD Symptom Severity in Military Personnel: A Randomized Clinical Trial.

    PubMed

    Foa, Edna B; McLean, Carmen P; Zang, Yinyin; Rosenfield, David; Yadin, Elna; Yarvis, Jeffrey S; Mintz, Jim; Young-McCaughan, Stacey; Borah, Elisa V; Dondanville, Katherine A; Fina, Brooke A; Hall-Clark, Brittany N; Lichner, Tracey; Litz, Brett T; Roache, John; Wright, Edward C; Peterson, Alan L

    2018-01-23

    Effective and efficient treatment is needed for posttraumatic stress disorder (PTSD) in active duty military personnel. To examine the effects of massed prolonged exposure therapy (massed therapy), spaced prolonged exposure therapy (spaced therapy), present-centered therapy (PCT), and a minimal-contact control (MCC) on PTSD severity. Randomized clinical trial conducted at Fort Hood, Texas, from January 2011 through July 2016 and enrolling 370 military personnel with PTSD who had returned from Iraq, Afghanistan, or both. Final follow-up was July 11, 2016. Prolonged exposure therapy, cognitive behavioral therapy involving exposure to trauma memories/reminders, administered as massed therapy (n = 110; 10 sessions over 2 weeks) or spaced therapy (n = 109; 10 sessions over 8 weeks); PCT, a non-trauma-focused therapy involving identifying/discussing daily stressors (n = 107; 10 sessions over 8 weeks); or MCC, telephone calls from therapists (n = 40; once weekly for 4 weeks). Outcomes were assessed before and after treatment and at 2-week, 12-week, and 6-month follow-up. Primary outcome was interviewer-assessed PTSD symptom severity, measured by the PTSD Symptom Scale-Interview (PSS-I; range, 0-51; higher scores indicate greater PTSD severity; MCID, 3.18), used to assess efficacy of massed therapy at 2 weeks posttreatment vs MCC at week 4; noninferiority of massed therapy vs spaced therapy at 2 weeks and 12 weeks posttreatment (noninferiority margin, 50% [2.3 points on PSS-I, with 1-sided α = .05]); and efficacy of spaced therapy vs PCT at posttreatment. Among 370 randomized participants, data were analyzed for 366 (mean age, 32.7 [SD, 7.3] years; 44 women [12.0%]; mean baseline PSS-I score, 25.49 [6.36]), and 216 (59.0%) completed the study. At 2 weeks posttreatment, mean PSS-I score was 17.62 (mean decrease from baseline, 7.13) for massed therapy and 21.41 (mean decrease, 3.43) for MCC (difference in decrease, 3.70 [95% CI,0.72 to 6.68]; P = .02

  10. Treatment initiation and dropout from prolonged exposure and cognitive processing therapy in a VA outpatient clinic.

    PubMed

    Kehle-Forbes, Shannon M; Meis, Laura A; Spoont, Michele R; Polusny, Melissa A

    2016-01-01

    Emerging data suggest that few veterans are initiating prolonged exposure (PE) and cognitive processing therapy (CPT) and dropout levels are high among those who do start the therapies. The goal of this study was to use a large sample of veterans seen in routine clinical care to 1) report the percent of eligible and referred veterans who (a) initiated PE/CPT, (b) dropped out of PE/CPT, (c) were early PE/CPT dropouts, 2) examine predictors of PE/CPT initiation, and 3) examine predictors of early and late PE/CPT dropout. We extracted data from the medical records of 427 veterans who were offered PE/CPT following an intake at a Veterans Health Administration (VHA) PTSD Clinical Team. Eighty-two percent (n = 351) of veterans initiated treatment by attending Session 1 of PE/CPT; among those veterans, 38.5% (n = 135) dropped out of treatment. About one quarter of veterans who dropped out were categorized as early dropouts (dropout before Session 3). No significant predictors of initiation were identified. Age was a significant predictor of treatment dropout; younger veterans were more likely to drop out of treatment than older veterans. Therapy type was also a significant predictor of dropout; veterans receiving PE were more likely to drop out late than veterans receiving CPT. Findings demonstrate that dropout from PE/CPT is a serious problem and highlight the need for additional research that can guide the development of interventions to improve PE/CPT engagement and adherence. (c) 2016 APA, all rights reserved).

  11. Micro-Raman spectroscopy of algae: composition analysis and fluorescence background behavior.

    PubMed

    Huang, Y Y; Beal, C M; Cai, W W; Ruoff, R S; Terentjev, E M

    2010-04-01

    Preliminary feasibility studies were performed using Stokes Raman scattering for compositional analysis of algae. Two algal species, Chlorella sorokiniana (UTEX #1230) and Neochloris oleoabundans (UTEX #1185), were chosen for this study. Both species were considered to be candidates for biofuel production. Raman signals due to storage lipids (specifically triglycerides) were clearly identified in the nitrogen-starved C. sorokiniana and N. oleoabundans, but not in their healthy counterparts. On the other hand, signals resulting from the carotenoids were found to be present in all of the samples. Composition mapping was conducted in which Raman spectra were acquired from a dense sequence of locations over a small region of interest. The spectra obtained for the mapping images were filtered for the wavelengths of characteristic peaks that correspond to components of interest (i.e., triglyceride or carotenoid). The locations of the components of interest could be identified by the high intensity areas in the composition maps. Finally, the time evolution of fluorescence background was observed while acquiring Raman signals from the algae. The time dependence of fluorescence background is characterized by a general power law decay interrupted by sudden high intensity fluorescence events. The decreasing trend is likely a result of photo-bleaching of cell pigments due to prolonged intense laser exposure, while the sudden high intensity fluorescence events are not understood. (c) 2009 Wiley Periodicals, Inc.

  12. Conservation of body calcium by increased dietary intake of potassium: A potential measure to reduce the osteoporosis process during prolonged exposure to microgravity

    NASA Technical Reports Server (NTRS)

    Nechay, Bohdan R.

    1989-01-01

    During the 1988 NASA Summer Faculty Fellowship Program, it was proposed that the loss of skeletal calcium upon prolonged exposure to microgravity could be explained, in part, by a renal maladjustment characterized by an increased urinary excretion of calcium. It was theorized that because the conservation of body fluids and electrolytes depends upon the energy of adenosine triphosphate and enzymes that control the use of its energy for renal ion transport, an induction of renal sodium and potassium-dependent adenosine triphosphatase (Na + K ATPase) by oral loading with potassium would increase the reabsorption of sodium directly and that of calcium indirectly, leading to improved hydration and to reduced calcium loss. Preliminary studies showed the following. Rats drinking water containing 0.2 M potassium chloride for six to 13 days excreted in urine 22 muEq of calcium and 135 muEq of sodium per 100 grams of body weight per day. The corresponding values for control rats drinking tap water were 43 muEq and 269 muEq respectively. Renal Na + K ATPase activity in potassium loaded rats was higher than in controls. Thus, oral potassium loading resulted in increased Na + K ATPase activity and diminished urinary excretion of calcium and of sodium as predicted by the hypothesis. An extension of these studies to humans has the potential of resulting in development of harmless, non-invasive, drug-free, convenient measures to reduce bone loss and other electrolyte and fluid problems in space travelers exposed to prolonged periods of microgravity.

  13. Ozone exposure of a weed community produces adaptive changes in seed populations of Spergula arvensis.

    PubMed

    Landesmann, Jennifer B; Gundel, Pedro E; Martínez-Ghersa, M Alejandra; Ghersa, Claudio M

    2013-01-01

    Tropospheric ozone is one of the major drivers of global change. This stress factor alters plant growth and development. Ozone could act as a selection pressure on species communities composition, but also on population genetic background, thus affecting life history traits. Our objective was to evaluate the consequences of prolonged ozone exposure of a weed community on phenotypic traits of Spergulaarvensis linked to persistence. Specifically, we predicted that the selection pressure exerted by high ozone concentrations as well as the concomitant changes in the weed community would drive population adaptive changes which will be reflected on seed germination, dormancy and longevity. In order to test seed viability and dormancy level, we conducted germination experiments for which we used seeds produced by S. arvensis plants grown within a weed community exposed to three ozone treatments during four years (0, 90 and 120 ppb). We also performed a soil seed bank experiment to test seed longevity with seeds coming from both the four-year ozone exposure experiment and from a short-term treatment conducted at ambient and added ozone concentrations. We found that prolonged ozone exposure produced changes in seed germination, dormancy and longevity, resulting in three S. arvensis populations. Seeds from the 90 ppb ozone selection treatment had the highest level of germination when stored at 75% RH and 25 °C and then scarified. These seeds showed the lowest dormancy level when being subjected to 5 ºC/5% RH and 25 ºC/75% followed by 5% RH storage conditions. Furthermore, ozone exposure increased seed persistence in the soil through a maternal effect. Given that tropospheric ozone is an important pollutant in rural areas, changes in seed traits due to ozone exposure could increase weed persistence in fields, thus affecting weed-crop interactions, which could ultimately reduce crop production.

  14. Ozone Exposure of a Weed Community Produces Adaptive Changes in Seed Populations of Spergula arvensis

    PubMed Central

    Landesmann, Jennifer B.; Gundel, Pedro E.; Martínez-Ghersa, M. Alejandra; Ghersa, Claudio M.

    2013-01-01

    Tropospheric ozone is one of the major drivers of global change. This stress factor alters plant growth and development. Ozone could act as a selection pressure on species communities composition, but also on population genetic background, thus affecting life history traits. Our objective was to evaluate the consequences of prolonged ozone exposure of a weed community on phenotypic traits of Spergula arvensis linked to persistence. Specifically, we predicted that the selection pressure exerted by high ozone concentrations as well as the concomitant changes in the weed community would drive population adaptive changes which will be reflected on seed germination, dormancy and longevity. In order to test seed viability and dormancy level, we conducted germination experiments for which we used seeds produced by S. arvensis plants grown within a weed community exposed to three ozone treatments during four years (0, 90 and 120 ppb). We also performed a soil seed bank experiment to test seed longevity with seeds coming from both the four-year ozone exposure experiment and from a short-term treatment conducted at ambient and added ozone concentrations. We found that prolonged ozone exposure produced changes in seed germination, dormancy and longevity, resulting in three S. arvensis populations. Seeds from the 90 ppb ozone selection treatment had the highest level of germination when stored at 75% RH and 25 °C and then scarified. These seeds showed the lowest dormancy level when being subjected to 5 ºC/5% RH and 25 ºC/75% followed by 5% RH storage conditions. Furthermore, ozone exposure increased seed persistence in the soil through a maternal effect. Given that tropospheric ozone is an important pollutant in rural areas, changes in seed traits due to ozone exposure could increase weed persistence in fields, thus affecting weed-crop interactions, which could ultimately reduce crop production. PMID:24086640

  15. Physiology of prolonged bed rest

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.

    1988-01-01

    Bed rest has been a normal procedure used by physicians for centuries in the treatment of injury and disease. Exposure of patients to prolonged bed rest in the horizontal position induces adaptive deconditioning responses. While deconditioning responses are appropriate for patients or test subjects in the horizontal position, they usually result in adverse physiological responses (fainting, muscular weakness) when the patient assume the upright posture. These deconditioning responses result from reduction in hydrostatic pressure within the cardiovascular system, virtual elimination of longitudinal pressure on the long bones, some decrease in total body metabolism, changes in diet, and perhaps psychological impact from the different environment. Almost every system in the body is affected. An early stimulus is the cephalic shift of fluid from the legs which increases atrial pressure and induces compensatory responses for fluid and electrolyte redistribution. Without countermeasures, deterioration in strength and muscle function occurs within 1 wk while increased calcium loss may continue for months. Research should also focus on drug and carbohydrate metabolism.

  16. Sinonasal Epithelial Wound Resealing in an In Vitro Model: Inhibition of Wound Closure with IL-4 Exposure

    PubMed Central

    Wise, Sarah K.; Den Beste, Kyle A.; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma

    2013-01-01

    Background Prolonged healing and persistent inflammation following surgery for rhinosinusitis impacts patient satisfaction and healthcare resources. Cytokines interleukin (IL)-4, 5, and 13 are important mediators in Th2 inflammatory rhinosinusitis. Decreased wound healing has been demonstrated with Th2 cytokine exposure, but this has not been extensively studied in sinonasal epithelium. We hypothesized that in vitro exposure of primary sinonasal epithelial cell cultures to Th2 inflammatory cytokine IL-4 and IL-13 would impair wound resealing and decrease expression of annexin A2 at the wound edge. Methods Following 24-hour exposure to IL-4, 5, or 13 versus controls, sterile linear mechanical wounds were created in primary sinonasal epithelial cultures (n = 12 wounds per condition). Wounds were followed for 36 hours or until complete closure and residual wound areas were calculated by image analysis. Group differences in annexin A2 were assessed by immunofluorescence labeling, confocal microscopy, and Western blots. Results Significant wound closure differences were identified across cytokine exposure groups (p<0.001). Mean percentage wound closure at the completion of the 36-hour timecourse was 98.41% ± 3.43% for control wounds versus 85.02% ± 18.46% for IL-4 exposed wounds. IL-13 did not significantly impair sinonasal epithelial wound resealing in vitro. Annexin A2 protein levels were decreased in IL-4 treated wounds when compared to control wounds (p<0.01). Conclusions Th2 cytokine IL-4 decreases sinonasal epithelial wound closure in vitro. Annexin A2 is also diminished with IL-4 exposure. This supports the hypothesis that IL-4 exposure impairs sinonasal epithelial wound healing and may contribute to prolonged healing in Th2 inflammatory rhinosinusitis. PMID:23468432

  17. Xenon Treatment Protects Against Cold Ischemia Associated Delayed Graft Function and Prolongs Graft Survival in Rats

    PubMed Central

    Zhao, H; Watts, H R; Chong, M; Huang, H; Tralau-Stewart, C; Maxwell, P H; Maze, M; George, A J T; Ma, D

    2013-01-01

    Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia–hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival. PMID:23710625

  18. Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats.

    PubMed

    Zhao, Hailin; Yoshida, Akira; Xiao, Wei; Ologunde, Rele; O'Dea, Kieran P; Takata, Masao; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

    2013-10-01

    Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

  19. Exploring physical exposures and identifying high-risk work tasks within the floor layer trade

    PubMed Central

    McGaha, Jamie; Miller, Kim; Descatha, Alexis; Welch, Laurie; Buchholz, Bryan; Evanoff, Bradley; Dale, Ann Marie

    2014-01-01

    Introduction Floor layers have high rates of musculoskeletal disorders yet few studies have examined their work exposures. This study used observational methods to describe physical exposures within floor laying tasks. Methods We analyzed 45 videos from 32 floor layers using Multimedia-Video Task Analysis software to determine the time in task, forces, postures, and repetitive hand movements for installation of four common flooring materials. We used the WISHA checklists to define exposure thresholds. Results Most workers (91%) met the caution threshold for one or more exposures. Workers showed high exposures in multiple body parts with variability in exposures across tasks and for different materials. Prolonged exposures were seen for kneeling, poor neck and low back postures, and intermittent but frequent hand grip forces. Conclusions Floor layers experience prolonged awkward postures and high force physical exposures in multiple body parts, which probably contribute to their high rates of musculoskeletal disorders. PMID:24274895

  20. Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants.

    PubMed

    Inatomi, Tadashi; Oue, Shinya; Ogihara, Tohru; Hira, Seigo; Hasegawa, Masashi; Yamaoka, Shigeo; Yasui, Masako; Tamai, Hiroshi

    2012-03-01

    The presence of microorganisms in gastric fluid in neonates at birth is postulated to reflect antenatal infection and also to be associated with the development of bronchopulmonary dysplasia (BPD). A logistic regression analysis, after controlling for other risk factors, indicated that Ureaplasma-positive infants were not at increased risk for moderate/severe BPD (adjusted odds ratio (OR): 2.58, 95% confidence interval (CI): 0.57-6.89, P = 0.12). However, the association between the presence of Ureaplasma species and the risk for moderate/severe BPD increased significantly in infants on mechanical ventilation (MV) ≥2 wk (adjusted OR: 4.17, 95% CI: 1.62-44.1, P = 0.009). An analysis using a lung injury marker indicated that Ureaplasma-positive infants with MV ≥2 wk, but not other infants, showed higher serum KL-6 levels in samples taken from cord blood, and that KL-6 levels increased time-dependently up to 4 wk of age. Antenatal exposure to Ureaplasma species induces lung injury prior to birth and synergistically contributes to the development of BPD in infants requiring prolonged MV (≥2 wk). We recovered gastric fluid specimens from 122 infants with gestational age (GA) <29 wk or birth weight <1,000 g to investigate whether these microorganisms influence respiratory outcome of BPD. A PCR analysis was used to detect urease and 16S ribosomal RNA (rRNA) genes to classify neonates into Ureaplasma-positive or Ureaplasma-negative infants.

  1. Characteristics of U.S. veterans who begin and complete prolonged exposure and cognitive processing therapy for PTSD.

    PubMed

    Mott, Juliette M; Mondragon, Sasha; Hundt, Natalie E; Beason-Smith, Melissa; Grady, Rebecca H; Teng, Ellen J

    2014-06-01

    This retrospective chart-review study examined patient-level correlates of initiation and completion of evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) among treatment-seeking U.S. veterans. We identified all patients (N = 796) in a large Veterans Affairs PTSD and anxiety clinic who attended at least 1 individual psychotherapy appointment with 1 of 8 providers trained in EBP. Within this group, 91 patients (11.4%) began EBP (either Cognitive Processing Therapy or Prolonged Exposure) and 59 patients (7.9%) completed EBP. The medical records of all EBP patients (n = 91) and a provider-matched sample of patients who received another form of individual psychotherapy (n = 66) were reviewed by 4 independent raters. Logistic regression analyses revealed that Iraq and Afghanistan veterans were less likely to begin EBP than veterans from other service eras, OR = 0.48, 95% CI = [0.24, 0.94], and veterans who were service connected for PTSD were more likely than veterans without service connection to begin EBP, OR = 2.33, 95% CI = [1.09, 5.03]. Among those who began EBP, Iraq and Afghanistan veteran status, OR = 0.09, 95% CI = [0.03, 0.30], and a history of psychiatric inpatient hospitalization, OR = 0.13, 95% CI = [0.03, 0.54], were associated with decreased likelihood of EBP completion. Published 2014. This article is a US Government work and is in the public domain in the USA.

  2. Human exposure to high natural background radiation: what can it teach us about radiation risks?

    PubMed Central

    Hendry, Jolyon H; Simon, Steven L; Wojcik, Andrzej; Sohrabi, Mehdi; Burkart, Werner; Cardis, Elisabeth; Laurier, Dominique; Tirmarche, Margot; Hayata, Isamu

    2014-01-01

    Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of 222Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case–control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case–control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors. PMID:19454802

  3. Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: recommendations for saturation divers.

    PubMed

    Deb, S K; Swinton, P A; Dolan, E

    2016-01-01

    Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised.

  4. Effects of prolonged exposure to moderate static magnetic field and its synergistic effects with alkaline pH on Enterococcus faecalis.

    PubMed

    Fan, Wei; Huang, Zhuo; Fan, Bing

    2018-02-01

    Static magnetic field (SMF) has been shown to biologically affect various microorganisms, but its effects on Enterococcus faecalis, which is associated with multiple dental infections, have not been reported yet. Besides, Enterococcus faecalis was found to be resistant to the alkaline environment provided by a major dental antimicrobial, calcium hydroxide. Therefore, the antibacterial activity of prolonged exposure to moderate SMF (170 mT) and its possible synergistic activity with alkaline pH (pH = 9) were evaluated in the study. The ability to form a biofilm under these conditions was examined by crystal violet assay. Real-time quantitative PCR was performed to evaluate the relative expression of stress (dnaK and groEL) and virulence (efaA, ace, gelE and fsrC) related genes. As the results indicated, cell proliferation was inhibited after 120 h of SMF exposure. What's more, the combined treatment of SMF and alkaline pH showed significantly improved antimicrobial action when compared to single SMF and alkaline pH treatment for more than 24 h and 72 h respectively. However, the ability to form a biofilm was also enhanced under SMF and alkaline pH treatments. SMF can induce stress response by up-regulating the expression of dnaK and elevate virulence gene expression (efaA and ace). These responses were more significant and more genes were up-regulated including groEL, gelE and fsrC when exposed to SMF and alkaline pH simultaneously. Hence, combination of SMF and alkaline pH could be a promising disinfection strategy in dental area and other areas associated with Enterococcus faecalis infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. [Prolonged exposure to atmospheric air pollution and mortality from respiratory causes].

    PubMed

    Eilstein, D

    2009-12-01

    Different designs can be used to analyze the relationships between respiratory mortality and long term exposure to atmospheric pollution: epidemiological studies (cohort, prevalence study) demonstrate the reality of the relationship and toxicological studies explain it. Cohort studies have the advantage of being able to take into account many confounding factors and thus avoid biases (which is not the case with prevalence studies), but require significant human and financial resources. They were first adopted in the US, but are now more often applied in Europe. The results are relatively consistent, as they all show a statistically significant association between an increase in particulate pollution and cardiopulmonary mortality. Mortality from lung cancer is also associated with long term exposition to particles and sometimes to ozone or nitrogen oxides. Cerebrovascular diseases and sudden death of young children have also been associated with particulate pollution. The relationships are more powerful for long term than short term exposure but are also linear and without threshold. In order to explain these effects (today the causality of the relationship is certain) there are many possible factors, particularly regarding particulate exposures: an increase in cardiovascular risk biomarkers (fibrinogen, white blood cells, and platelets), atherosclerosis, chronic inflammation of lung tissues increased by acute exposure, etc. More and more studies address the interaction between gene and environment and even epigenetic phenomena which could be responsible of these effects. Public Health impact could be quantified. The European E&H surveillance program Apheis, for example, estimated that if PM2.5 levels remained below 15 microg/m(3), a 30 year old person could see his life expectancy increased by 1 month to 2 years, depending on the studied city. Finally, mortality is not the only relevant indicator for health effects of air pollution. ISAAC studies address asthma

  6. Ecosystem Consequences of Prolonged Ozone Pollution in the Southern Sierra Nevada

    NASA Astrophysics Data System (ADS)

    Cousins, S.; Battles, J. J.; Cisneros, R.; Esperanza, A.; Swenson, D.

    2015-12-01

    While acute O3 exposure is widely known to damage plant tissues, the chronic effects on long lived organisms such as trees remain unclear. In the southern Sierra Nevada, O3 pollution has afflicted pine-dominated forests for over 40 years. Here we report the results of a long-term study of O3 impact on tree injury, growth, and mortality. Our study employed a network of forest plots along a gradient of O3 pollution with recurring measurements from 1991-2012. Over the same period and locations, summer O3 was monitored via partnership with USNPS and USFS, making this one of the longest known ecosystem studies of O3 pollution and its effects. We found that exposure at the most polluted sites declined 33%, from a W126 index of 20.12 ppm-hrs in 1992 to 13.5 ppm-hrs in 2012. The severity of foliar pollution damage at these sites also declined, from 43.9 on the 0-100 Ozone Injury Index (OII) scale to 34.2, a drop of 22%. At locations with lower O3 exposure, damage declined from OII of 16.9 to 9.2. Mean annual tree mortality rates over the 20 year period, calculated with a profile likelihood approach, were 0.5%/yr (95% CI 0.3 to 0.8 %/yr). This rate is similar to that of healthy canopy trees in similar unpolluted stands. However, low and declining tree growth rates reveal possible ecosystem impacts of prolonged exposure to pollution. Across affected sites, mean relative growth rates were 1.1%/yr in 1991-2000, and just 0.9%/yr in 2000-2011, a decline of 15.6% in the second decade. Initial analyses suggest that tree damage is positively correlated with June-October O3, as indicated by previous studies. Further analysis will explore the drivers of ecosystem impacts and roles of other natural and anthropogenic stressors, including variation in climatic water deficit. Understanding the consequences of prolonged O3 exposure on both individual trees and complex forest ecosystems helps identify the hidden environmental costs of tropospheric O3 and potential benefits of cleaner air.

  7. Quantification of Acute Vocal Fold Epithelial Surface Damage with Increasing Time and Magnitude Doses of Vibration Exposure

    PubMed Central

    Kojima, Tsuyoshi; Van Deusen, Mark; Jerome, W. Gray; Garrett, C. Gaelyn; Sivasankar, M. Preeti; Novaleski, Carolyn K.; Rousseau, Bernard

    2014-01-01

    Because the vocal folds undergo repeated trauma during continuous cycles of vibration, the epithelium is routinely susceptible to damage during phonation. Excessive and prolonged vibration exposure is considered a significant predisposing factor in the development of vocal fold pathology. The purpose of the present study was to quantify the extent of epithelial surface damage following increased time and magnitude doses of vibration exposure using an in vivo rabbit phonation model. Forty-five New Zealand white breeder rabbits were randomized to nine groups and received varying phonation time-doses (30, 60, or 120 minutes) and magnitude-doses (control, modal intensity phonation, or raised intensity phonation) of vibration exposure. Scanning electron microscopy and transmission electron microscopy was used to quantify the degree of epithelial surface damage. Results revealed a significant reduction in microprojection density, microprojection height, and depth of the epithelial surface with increasing time and phonation magnitudes doses, signifying increased epithelial surface damage risk with excessive and prolonged vibration exposure. Destruction to the epithelial cell surface may provide significant insight into the disruption of cell function following prolonged vibration exposure. One important goal achieved in the present study was the quantification of epithelial surface damage using objective imaging criteria. These data provide an important foundation for future studies of long-term tissue recovery from excessive and prolonged vibration exposure. PMID:24626217

  8. [Representation of Internal Medicine in G-DRG System - Analysis of Reasons for Prolonged Length of Stay].

    PubMed

    Siam, Kristina; Roeder, Norbert; Fölsch, Ulrich R; Spies, Hans-Friedrich

    2017-08-01

    Background  There is an ongoing discussion within the German Society of Internal Medicine (DGIM) and the Professional Association of German Internists (BDI) about the appropriate depiction and remuneration of internal medicine in the G-DRG. Method  Therefore, cases with a significantly prolonged length of stay were analyzed in a multicenter study. 124 cases from 6 hospitals were collected for evaluation. Results  The results show that the observed prolongation of hospitalization was mainly due to medical reasons. Discussion  Thus, patients with unclear symptoms and consequently need for a thorough workup could not be identified to cause longer inpatient stay. Instead, treatment complications and comorbidities led to extended hospitalization. The results also reveal prolonged hospitalization as a consequence of unsettled or delayed postdischarge care e. g. in rehabilitation facilities. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Development of a Decision Support System for Analysis and Solutions of Prolonged Standing in the Workplace

    PubMed Central

    Halim, Isa; Arep, Hambali; Kamat, Seri Rahayu; Abdullah, Rohana; Omar, Abdul Rahman; Ismail, Ahmad Rasdan

    2014-01-01

    Background Prolonged standing has been hypothesized as a vital contributor to discomfort and muscle fatigue in the workplace. The objective of this study was to develop a decision support system that could provide systematic analysis and solutions to minimize the discomfort and muscle fatigue associated with prolonged standing. Methods The integration of object-oriented programming and a Model Oriented Simultaneous Engineering System were used to design the architecture of the decision support system. Results Validation of the decision support system was carried out in two manufacturing companies. The validation process showed that the decision support system produced reliable results. Conclusion The decision support system is a reliable advisory tool for providing analysis and solutions to problems related to the discomfort and muscle fatigue associated with prolonged standing. Further testing of the decision support system is suggested before it is used commercially. PMID:25180141

  10. Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

    PubMed Central

    Chiarugi, Alberto; Pitari, Giovanni Mario; Costa, Rosa; Ferrante, Margherita; Villari, Loredana; Amico-Roxas, Matilde; Godfraind, Théophile; Bianchi, Alfredo; Salomone, Salvatore

    2002-01-01

    We investigated the effects of prolonged exposure to copper (Cu2+) on vascular functioning of isolated rat aorta. Aortic rings were exposed to CuSO4 (3–24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu2+. Exposure to 2 μM Cu2+ in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 μM PE by 30% (P<0.05) and impaired the relaxant response to 3 μM ACh or 1 μM A23187 (ACh, from 65.7±7.1 to 6.2±1.1%, n=8; A23187, from 74.6±8.2 to 12.0±0.8%, n=6; P<0.01 for both). Cu2+ exposure did not affect the relaxant response to NO-donors. Impairment of vasorelaxation appeared 3 h after incubation with 2 μM Cu2+ and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2±6.4%, n=10, P<0.01 vs Cu2+ alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. Twenty-four hour-exposure to 2 μM Cu2+ did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8±1.1 to 18.9±2.9 ng mg−1 wet weight, n=8; P<0.01. Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu2+ impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. PMID:12163352

  11. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    PubMed

    Mao, Sheng-Chun; Chang, Chih-Hua; Wu, Chia-Chen; Orejarena, M Juliana; Orejanera, Maria Juliana; Manzoni, Olivier J; Gean, Po-Wu

    2013-01-01

    Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  12. Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.

    PubMed

    Verma, Preeti; Prajapati, Sunil K; Yadav, Rajbharan; Senyschyn, Danielle; Shea, Peter R; Trevaskis, Natalie L

    2016-11-07

    hydrated proniosomes can prolong systemic drug exposure over 3 days and provide a sustained therapeutic effect. The developed proniosomes represent a novel approach to treat acute pain and inflammation with the potential to be administered as a single intravenous dose by a clinician at the time of injury or surgery that provides adequate relief for several days and reduces fluctuations in therapy. Similar systems loaded with different drugs have potential for broader application in anesthesia, anti-infective, antiemetic, and cancer therapy.

  13. Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

    PubMed

    TruneČka, P; Klempnauer, J; Bechstein, W O; Pirenne, J; Friman, S; Zhao, A; Isoniemi, H; Rostaing, L; Settmacher, U; Mönch, C; Brown, M; Undre, N; Tisone, G

    2015-07-01

    DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc.

  14. Prolonged bradycardia, asystole and outcome of high spinal cord injury patients: Risk factors and management

    PubMed Central

    Shaikh, Nissar; Rhaman, M. A.; Raza, Ali; Shabana, Adel; Malstrom, Mahommad Faisal; Al-Sulaiti, Ghanem

    2016-01-01

    Background: High spinal cord injury (HSCI) is one of the devastating traumatic injuries. 80% of these patients are young male, and 93% will have major neurological disabilities. There is a paucity of literature about prolonged bradycardia in HSCI patients. The aim of this study was to know the prevalence, risk factors, precipitating factors for prolonged bradycardia in the HSCI patients. Materials and Methods: All patients who were admitted to the Intensive Care Unit (ICU) of a tertiary hospital, with spinal cord injury above level of dorsal (D4) were enrolled in this study prospectively. Patient's demographic data, mechanism, level and type of spinal injury, associated injuries, injury severity score (ISS), spinal shock, vasopressors used, time of occurrence of bradycardia, treatment for bradycardia, precipitating as well as risk factors and outcome were recorded. Results: During the study period, a total of 138 patients were admitted to the ICU with HSCI. Majority of patients were male. The most frequently associated injury in these patients was skeletal fractures (38.4%). Most common complication was pneumonia 56 (41%). Forty-five (33%) of the total patients had prolonged bradycardia; 87% of these patients had pneumonia when bradycardia occurred. 53.4% had cardiac asystole. 29 (21%) patients had bradycardia at the time of endotracheal suctioning, whereas 27 (20%) patients developed bradycardia at the time of positioning. Majority of the patients were managed conservatively. Those HSCI patients who developed prolonged bradycardia, their ISS score was statistically higher, ICU and hospital stay was significantly higher compared with those HSCI patient who did not have prolonged bradycardia. Multivariate analysis revealed that hypotension on admission; pneumonia, and tracheostomy were risk factors for the development of prolonged bradycardia in HSCI patients. Conclusion: Prolonged bradycardia was associated with significantly higher incidence of asystole

  15. Prolonged CT urography in duplex kidney.

    PubMed

    Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

    2016-05-13

    Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

  16. Stimulation of cardiovascular adaptability during prolonged space exposure

    NASA Technical Reports Server (NTRS)

    Gorman, H. A.

    1971-01-01

    The deconditioning effects of weightlessness on the cardiovascular system of astronauts are discussed. It is believed that man cannot tolerate indefinite exposure to weightlessness without considerable circulatory deterioration. Analyses of data collected from space flights to date substantiate these beliefs, and confirm the fact that some form of compensation must be provided to keep the cardiovascular system of space travelers properly conditioned. Sequential pulsatile devices were investigated to produce periodic hydrostatic pressure gradients in the venous system of eight subhuman primates. Intermittent venous pooling of blood in the extremities triggers and stimulates the vascular reflex mechanisms of the cardiovascular system that may have significant benefits in maintaining the circulatory system in proper tone under weightless conditions. Electrocardiograms, blood pressure measurements, cardiac output and stroke volume determinations were used to evaluate the efficiency of the described technique. Results were amazingly consistent to indicate an efficient system for intermittently exercising the heart within safe and medically acceptable limits.

  17. Xenon treatment protects against cold ischemia associated delayed graft function and prolongs graft survival in rats.

    PubMed

    Zhao, H; Watts, H R; Chong, M; Huang, H; Tralau-Stewart, C; Maxwell, P H; Maze, M; George, A J T; Ma, D

    2013-08-01

    Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia-hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. Post-training Beliefs, Intentions, and Use of Prolonged Exposure Therapy by Clinicians in the Veterans Health Administration.

    PubMed

    Ruzek, J I; Eftekhari, A; Crowley, J; Kuhn, E; Karlin, B E; Rosen, C S

    2017-01-01

    To examine how changes in beliefs during the training process predict adoption of prolonged exposure therapy (PE) by veterans health administration clinicians who received intensive training in this evidence-based treatment. Participants completed a 4-day PE workshop and received expert consultation as they used PE with two or more training cases. Participants were surveyed prior to the workshop, after the workshop, after case consultation (n = 1.034), and 6 months after training (n = 810). Hierarchical regression was used to assess how pre-training factors, and changes in beliefs during different stages of training incrementally predicted post-training intent to use PE and how many patients clinicians were treating with PE 6 months after training. Post-training intent to use PE was high (mean = 6.2, SD = 0.81 on a 1-7 scale), yet most participants treated only 1 or 2 patients at a time with PE. Pre-training factors predicted intent to use and actual use of PE. Changes in beliefs during the workshop had statistically significant yet modest effects on intent and use of PE. Changes in beliefs during case consultation had substantial effects on intent and actual use of PE. Pre-training factors and changes in beliefs during training (especially during case consultation) influence clinicians' adoption of PE. Use of PE was influenced not only by its perceived clinical advantages/disadvantages, but also by contextual factors (working in a PTSD specialty clinic, perceived control over one's schedule, and ability to promote PE to patients and colleagues).

  19. Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Burroughs, S.F.; Johnson, G.J.

    beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of (14C)-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; butmore » no irreversible inhibition of alpha 2 adrenergic receptors, measured with (3H)-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist (3H)-U46619 and antagonist (3H)-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ((Ca2+)i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in (Ca2+)i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane.« less

  20. Low extracellular potassium prolongs repolarization and evokes early afterdepolarization in human induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Kuusela, Jukka; Larsson, Kim; Shah, Disheet; Prajapati, Chandra; Aalto-Setälä, Katriina

    2017-06-15

    Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K + Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K + concentration ([K + ] Ex ) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K + ] Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K + ] Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K + ] Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K + ] Ex and provide a platform to study acquired LQTS. © 2017. Published by The Company of Biologists Ltd.

  1. Exposure of human melanocytes to UVB twice and subsequent incubation leads to cellular senescence and senescence-associated pigmentation through the prolonged p53 expression.

    PubMed

    Choi, Suh-Yeon; Bin, Bum-Ho; Kim, Wanil; Lee, Eunkyung; Lee, Tae Ryong; Cho, Eun-Gyung

    2018-06-01

    Ultraviolet radiation (UVR) is a well-known factor in skin aging and pigmentation, and daily exposure to subcytotoxic doses of UVR might accelerate senescence and senescence-associated phenomena in human melanocytes. To establish an in vitro melanocyte model to mimic the conditions of repeated exposure to subcytotoxic doses of UVB irradiation and to investigate key factor(s) for melanocyte senescence and senescence-associated phenomena. Human epidermal melanocytes were exposed twice with 20 mJ/cm 2 UVB over a 24-h interval and subsequently cultivated for 2 weeks. Senescent phenotypes were addressed morphologically, and by measuring the senescence-associated β-galactosidase (SA-β-Gal) activity, cell proliferation capacity with cell cycle analysis, and melanin content. The established protocol successfully induced melanocyte senescence, and senescent melanocytes accompanied hyperpigmentation. Prolonged expression of p53 was responsible for melanocyte senescence and hyperpigmentation, and treatment with the p53-inhibitor pifithrin-α at 2-weeks post-UVB irradiation, but not at 48 h, significantly reduced melanin content along with decreases in tyrosinase levels. Melanocyte senescence model will be useful for studying the long-term effects of UVB irradiation and pigmentation relevant to physiological photoaging, and screening compounds effective for senescence-associated p53-mediated pigmentation. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  2. Study of the GERDA Phase II background spectrum

    NASA Astrophysics Data System (ADS)

    Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevzik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

    2017-09-01

    The Gerda experiment, located at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy, searches for the neutrinoless double beta (0νββ) decay of 76Ge. Gerda Phase II is aiming to reach a sensitivity for the 0νββ half life of 1026 yr in ˜ 3 years of physics data taking with 100 kg·yr of exposure and a background index of ˜ 10-3 cts/(keV·kg·yr). After 6 months of acquisition a first data release with 10.8 kg·yr of exposure is performed, showing that the design background is achieved. In this work a study of the Phase II background spectrum, the main spectral structures and the background sources will be presented and discussed.

  3. Efficacy of smoking cessation therapy alone or integrated with prolonged exposure therapy for smokers with PTSD: Study protocol for a randomized controlled trial.

    PubMed

    Powers, Mark B; Kauffman, Brooke Y; Kleinsasser, Anne L; Lee-Furman, Eunjung; Smits, Jasper A J; Zvolensky, Michael J; Rosenfield, David

    2016-09-01

    Posttraumatic stress disorder (PTSD) is related to an increased risk of smoking cessation failure. In fact, the quit rate in smokers with PTSD (23.2%) is one of the lowest of all mental disorders. Features of PTSD that contribute to smokers' progression to nicotine dependence and cessation relapse include negative affect, fear, increased arousal, irritability, anger, distress intolerance, and anxiety sensitivity. Anxiety sensitivity is higher in people with PTSD than in any other anxiety disorder except for panic disorder. High anxiety sensitivity is uniquely associated with greater odds of lapse and relapse during quit attempts. Distress intolerance, a perceived or behavioral tendency to not tolerate distress, is related to both the maintenance of PTSD and problems in quitting smoking. Prolonged exposure (PE) and interoceptive exposure (IE) reduce PTSD symptoms, distress intolerance, and anxiety sensitivity. Thus, they emerge as promising candidates to augment standard smoking cessation interventions for individuals with PTSD. The present study tests a 12-session specialized treatment for smokers with PTSD. This Integrated PTSD and Smoking Treatment (IPST) combines cognitive-behavioral therapy and nicotine replacement treatment for smoking cessation (standard care; SC) with PE to target PTSD symptoms and IE to reduce anxiety sensitivity and distress intolerance. Adult smokers (N=80) with PTSD will be randomly assigned to either: (1) IPST or (2) SC. Primary outcomes are assessed at weeks 0, 6, 8, 10, 14, 16, 22, and 30. Copyright © 2016. Published by Elsevier Inc.

  4. Elevated Radiation Exposure Associated With Above Surface Flat Detector Mini C-Arm Use.

    PubMed

    Martin, Dennis P; Chapman, Talia; Williamson, Christopher; Tinsley, Brian; Ilyas, Asif M; Wang, Mark L

    2017-11-01

    This study aims to test the hypothesis that: (1) radiation exposure is increased with the intended use of Flat Surface Image Intensifier (FSII) units above the operative surface compared with the traditional below-table configuration; (2) this differential increases in a dose-dependent manner; and (3) radiation exposure varies with body part and proximity to the radiation source. A surgeon mannequin was seated at a radiolucent hand table, positioned for volar distal radius plating. Thermoluminescent dosimeters measured exposure to the eyes, thyroid, chest, hand, and groin, for 1- and 15-minute trials from a mini C-arm FSII unit positioned above and below the operating surface. Background radiation was measured by control dosimeters placed within the operating theater. At 1-minute of exposure, hand and eye dosages were significantly greater with the flat detector positioned above the table. At 15-minutes of exposure, hand radiation dosage exceeded that of all other anatomic sites with the FSII in both positions. Hand exposure was increased in a dose-dependent manner with the flat detector in either position, whereas groin exposure saw a dose-dependent only with the flat detector beneath the operating table. These findings suggest that the surgeon's hands and eyes may incur greater radiation exposure compared with other body parts, during routine mini C-arm FSII utilization in its intended position above the operating table. The clinical impact of these findings remains unclear, and future long-term radiation safety investigation is warranted. Surgeons should take precautions to protect critical body parts, particularly when using FSII technology above the operating with prolonged exposure time.

  5. The role of nitric oxide synthase in reduced vasocontractile responsiveness induced by prolonged α1-adrenergic receptor stimulation in rat thoracic aorta

    PubMed Central

    Gürdal, Hakan; Can, Alp; Uğur, Mehmet

    2005-01-01

    Prolonged exposure (6–12 h) of rat aorta to alpha1-adrenergic receptor (α1AR) agonist phenylephrine (Phe) leads to a decrease in α1AR-mediated vasoconstriction. This reduced responsiveness to α1AR stimulation was strongly dependent on the intactness of the endothelium. We examined the effect of Phe on nitric oxide synthase (NOS) activity by measuring the conversion of [3H]L-arginine to [3H]L-citrulline in rat aorta or in endothelial cells isolated from rat aorta. Phe stimulation increased NOS activity in control aortas. This response was antagonized by prazosin. However, Phe increased neither the activity of NOS nor intracellular Ca2+ in the isolated endothelial cells from the control aortas, whereas acetylcholine (Ach) was able to stimulate both responses in these cells. This result suggests that Phe stimulates α1AR on vascular smooth muscle cells and has an indirect influence on endothelial cells to increase NOS activity. In Phe-exposed aortic rings, basal NOS activity was found to have increased compared to vehicle-exposed control rings. Stimulation with Phe or Ach caused a small increase over basal NOS activity in these preparations. Prolonged exposure to Phe also caused an enhancement of Ach-mediated vasorelaxation in rat aorta. Immunoblot and reverse transcription–polymerase chain reaction experiments showed that prolonged exposure of rat aorta to Phe resulted in an increased expression of eNOS, but not iNOS. This increase was antagonized by nonselective antagonist prazosin. Immunohistochemical staining experiments also showed that expression of eNOS increased in endothelial cells after Phe exposure of the aortas. These results, all together, showed that prolonged exposure of rat aorta to α1AR agonist Phe enhanced the expression of eNOS and basal NOS activity, which probably causes a decreased vasocontractile response to Phe or to other agonists such as 5HT (5-hydroxytryptamine) in rat aorta. This phenomenon can be considered more as a functional

  6. Prolonged menstrual cycles in female workers exposed to ethylene glycol ethers in the semiconductor manufacturing industry.

    PubMed

    Hsieh, G-Y; Wang, J-D; Cheng, T-J; Chen, P-C

    2005-08-01

    It has been shown that female workers exposed to ethylene glycol ethers (EGEs) in the semiconductor industry have higher risks of spontaneous abortion, subfertility, and menstrual disturbances, and prolonged waiting time to pregnancy. To examine whether EGEs or other chemicals are associated with long menstrual cycles in female workers in the semiconductor manufacturing industry. Cross-sectional questionnaire survey during the annual health examination at a wafer manufacturing company in Taiwan in 1997. A three tiered exposure-assessment strategy was used to analyse the risk. A short menstrual cycle was defined to be a cycle less than 24 days and a long cycle to be more than 35 days. There were 606 valid questionnaires from 473 workers in fabrication jobs and 133 in non-fabrication areas. Long menstrual cycles were associated with workers in fabrication areas compared to those in non-fabrication areas. Using workers in non-fabrication areas as referents, workers in photolithography and diffusion areas had higher risks for long menstrual cycles. Workers exposed to EGEs and isopropanol, and hydrofluoric acid, isopropanol, and phosphorous compounds also showed increased risks of a long menstrual cycle. Exposure to multiple chemicals, including EGEs in photolithography, might be associated with long menstrual cycles, and may play an important role in a prolonged time to pregnancy in the wafer manufacturing industry; however, the prevalence in the design, possible exposure misclassification, and chance should be considered.

  7. Comparing Virtual Reality Exposure Therapy to Prolonged Exposure in the Treatment of Soldiers with PTSD

    DTIC Science & Technology

    2014-06-01

    Type I alpha should be discussed in relation to the findings for multiple primary hypothesis tests conducted . o The hypotheses indicated in the...memory during exposure. However, there is limited research on the effectiveness of either treatment with active duty military personnel and there are...VRE or were assigned to a minimal attention wait list. All assessments were conducted by a psychologist blind to treatment group. External

  8. [Brain function recovery after prolonged posttraumatic coma].

    PubMed

    Klimash, A V; Zhanaidarov, Z S

    2016-01-01

    To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

  9. [Pathophysiology of prolonged hypokinesia].

    PubMed

    Kovalenko, E A

    1976-01-01

    Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

  10. The impact of prolonged violent video-gaming on adolescent sleep: an experimental study.

    PubMed

    King, Daniel L; Gradisar, Michael; Drummond, Aaron; Lovato, Nicole; Wessel, Jason; Micic, Gorica; Douglas, Paul; Delfabbro, Paul

    2013-04-01

    Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep. © 2012 European Sleep Research Society.

  11. Prolonged post-hyperventilation apnea in two young adults with hyperventilation syndrome

    PubMed Central

    2013-01-01

    Background The prognosis of hyperventilation syndrome (HVS) is generally good. However, it is important to proceed with care when treating HVS because cases of death following hyperventilation have been reported. This paper was done to demonstrate the clinical risk of post-hyperventilation apnea (PHA) in patients with HVS. Case presentation We treated two patients with HVS who suffered from PHA. The first, a 21-year-old woman, had a maximum duration of PHA of about 3.5 minutes and an oxygen saturation (SpO2) level of 60%. The second patient, a 22-year-old woman, had a maximum duration of PHA of about 3 minutes and an SpO2 level of 66%. Both patients had loss of consciousness and cyanosis. Because there is no widely accepted regimen for treating patients with prolonged PHA related to HVS, we administered artificial ventilation to both patients using a bag mask and both recovered without any after effects. Conclusion These cases show that some patients with HVS develop prolonged PHA or severe hypoxia, which has been shown to lead to death in some cases. Proper treatment must be given to patients with HVS who develop PHA to protect against this possibility. If prolonged PHA or severe hypoxemia arises, respiratory assistance using a bag mask must be done immediately. PMID:23594702

  12. Cochlear Damages Caused by Vibration Exposure

    PubMed Central

    Moussavi Najarkola, Seyyed Ali; Khavanin, Ali; Mirzaei, Ramazan; Salehnia, Mojdeh; Muhammadnejad, Ahad

    2013-01-01

    Background Many industrial devices have an excessive vibration which can affect human body systems. The effect of vibration on cochlear histology has been as a debatable problem in occupational health and medicine. Objectives Due to limitation present in human studies, the research was conducted to survey the influence of vibration on cochlear histology in an animal model. Materials and Methods Twelve albino rabbits were experimented as: Vibration group (n = 6; exposed to 1.0 m.s-2 r.m.s vertical whole-body vibration at 4 - 8 Hz for 8 hours per day during 5 consecutive days) versus Control group (n = 6; the same rabbits without vibration exposure). After finishing the exposure scenario, all rabbits were killed by CO2 inhalation; their cochleae were extracted and fixed in 10% formaldehyde for 48 hours, decalcified by 10% nitric acid for 24 hours. Specimens were dehydrated, embedded, sectioned 5 µm thick and stained with Hematoxylin and Eosin for light microscopy observations. Results Severely hydropic degenerated and vacuolated inner hair cells (IHCs) were observed in vibration group compared to the control group. Inter and intracellular edema was appeared in supporting cells (SC). Nuclei of outer hair cells (OHCs) seemed to be pyknotic. Slightly thickened basilar membrane (BM) was probably implied to inter cellular edematous. Tectorial Membrane (TM) was not affected pathologically. Conclusions Whole-body vibration could cause cochlear damages in male rabbits, though vibration-induced auditory functional effects might be resulted as subsequent outcome of prolonged high level vibration exposures. PMID:24616783

  13. The impacts of repeated cold exposure on insects.

    PubMed

    Marshall, Katie E; Sinclair, Brent J

    2012-05-15

    Insects experience repeated cold exposure (RCE) on multiple time scales in natural environments, yet the majority of studies of the effects of cold on insects involve only a single exposure. Three broad groups of experimental designs have been employed to examine the effects of RCE on insect physiology and fitness, defined by the control treatments: 'RCE vs cold', which compares RCE with constant cold conditions; 'RCE vs warm', which compares RCE with constant warm conditions; and 'RCE vs matched cold' which compares RCE with a prolonged period of cold matched by time to the RCE condition. RCE are generally beneficial to immediate survival, and increase cold hardiness relative to insects receiving a single prolonged cold exposure. However, the effects of RCE depend on the study design, and RCE vs warm studies cannot differentiate between the effects of cold exposure in general vs RCE in particular. Recent studies of gene transcription, immune function, feeding and reproductive output show that the responses of insects to RCE are distinct from the responses to single cold exposures. We suggest that future research should attempt to elucidate the mechanistic link between physiological responses and fitness parameters. We also recommend that future RCE experiments match the time spent at the stressful low temperature in all experimental groups, include age controls where appropriate, incorporate a pilot study to determine time and intensity of exposure, and measure sub-lethal impacts on fitness.

  14. Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong

    NASA Astrophysics Data System (ADS)

    Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward

    2017-11-01

    Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights

  15. Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong.

    PubMed

    Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward

    2017-11-01

    Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights

  16. Can polychlorinated biphenyl (PCB) signatures and enantiomer fractions be used for source identification and to age date occupational exposure?

    PubMed

    Megson, David; Focant, Jean-Françios; Patterson, Donald G; Robson, Matthew; Lohan, Maeve C; Worsfold, Paul J; Comber, Sean; Kalin, Robert; Reiner, Eric; O'Sullivan, Gwen

    2015-08-01

    Detailed polychlorinated biphenyl (PCB) signatures and chiral Enantiomer Fractions (EFs) of CB-95, CB-136 and CB-149 were measured for 30 workers at a transformer dismantling plant. This was undertaken to identify sources of exposure and investigate changes to the PCB signature and EFs over different exposure periods. Approximately 1.5 g of serum was extracted and PCB signatures were created through analysis by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS) and EFs calculated following analysis by gas chromatography with high resolution mass spectrometry (GC-HRMS). A total of 84 PCBs were identified in the serum samples with concentrations of the 7 indicator PCBs ranging from 11-350 ng g(-1) of serum (1.2-39 μg g(-1) lipid). The PCB signatures were interpreted using principal component analysis (PCA) which was able to distinguish workers with background or recent minimal exposure from those with prolonged occupational exposure. Occupationally exposed individuals had a similar PCB profile to Aroclor A1260. However, individuals with prolonged exposure had depleted proportions of several PCB congeners that are susceptible to metabolism (CB-95, CB-101 and CB-151) and elevated proportions of PCBs that are resistant to metabolism (CB-74, CB-153, CB-138 and CB-180). The results also identified a third group of workers with elevated proportions of CB-28, CB-60, CB-66, CB-74, CB-105 and CB-118 who appeared to have been exposed to an additional source of PCBs. The results show near complete removal of the CB-95 E2 enantiomer in some samples, indicating that bioselective metabolism or preferential excretion of one enantiomer occurs in humans. By considering PCB concentrations along with detailed congener specific signatures it was possible to identify different exposure sources, and gain an insight into both the magnitude and duration of exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy.

    PubMed

    Amoroso, Timothy; Workman, Michael

    2016-07-01

    Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments. The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials. It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges' g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges' g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD. © The Author(s) 2016.

  18. Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jimenez-Jimenez, F.J.; Mateo, D.; Gimenez-Roldan, S.

    1992-01-01

    Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedatingmore » the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.« less

  19. Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

    PubMed Central

    Jose, Sophie; Hamzah, Lisa; Campbell, Lucy J.; Hill, Teresa; Fisher, Martin; Leen, Clifford; Gilson, Richard; Walsh, John; Nelson, Mark; Hay, Phillip; Johnson, Margaret; Chadwick, David; Nitsch, Dorothea; Jones, Rachael; Sabin, Caroline A.; Post, Frank A.; Ainsworth, Jonathan; Anderson, Jane; Babiker, Abdel; Chadwick, David; Delpech, Valerie; Dunn, David; Fisher, Martin; Gazzard, Brian; Gilson, Richard; Gompels, Mark; Hay, Phillip; Hill, Teresa; Johnson, Margaret; Kegg, Stephen; Leen, Clifford; Nelson, Mark; Orkin, Chloe; Palfreeman, Adrian; Phillips, Andrew; Pillay, Deenan; Post, Frank; Sabin, Caroline; Sachikonye, Memory; Schwenk, Achim; Walsh, John; Hill, Teresa; Huntington, Susie; Josie, Sophie; Phillips, Andrew; Sabin, Caroline; Thornton, Alicia; Dunn, David; Glabay, Adam; Orkin, C.; Garrett, N.; Lynch, J.; Hand, J.; de Souza, C.; Fisher, M.; Perry, N.; Tilbury, S.; Churchill, D.; Gazzard, B.; Nelson, M.; Waxman, M.; Asboe, D.; Mandalia, S.; Delpech, V.; Anderson, J.; Munshi, S.; Korat, H.; Poulton, M.; Taylor, C.; Gleisner, Z.; Campbell, L.; Babiker, Abdel; Dunn, David; Glabay, Adam; Gilson, R.; Brima, N.; Williams, I.; Schwenk, A.; Ainsworth, J.; Wood, C.; Miller, S.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Puradiredja, D.; Walsh, J.; Weber, J.; Ramzan, F.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Gompels, M.; Allan, S.; Palfreeman, A.; Moore, A.; Chadwick, D.; Wakeman, K.; Kegg, Stephen; Main, Paul; Mitchell; Hunter; Sachikonye, Memory; Hay, Phillip; Dhillon, Mandip

    2014-01-01

    Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided. PMID:24585896

  20. Management of children with prolonged diarrhea

    PubMed Central

    Giannattasio, Antonietta; Guarino, Alfredo; Lo Vecchio, Andrea

    2016-01-01

    Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded. PMID:26962439

  1. Management of children with prolonged diarrhea.

    PubMed

    Giannattasio, Antonietta; Guarino, Alfredo; Lo Vecchio, Andrea

    2016-01-01

    Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded.

  2. Home-based detoxification for neonatal abstinence syndrome reduces length of hospital admission without prolonging treatment.

    PubMed

    Smirk, Cameron L; Bowman, Ellen; Doyle, Lex W; Kamlin, Omar

    2014-06-01

    Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome, secondary to in utero chemical exposure and characterised by tremor, irritability and feed intolerance. It often requires prolonged hospital treatment and separation of families. Outpatient therapy may reduce this burden, but current literature is sparse. This review aimed to evaluate the safety and efficacy of our home-based detoxification programme and compare it with standard inpatient care. Infants requiring treatment for NAS between January 2004 and December 2010 were reviewed. Data on demographics, drug exposure, length of stay and type of therapy were compared between infants selected for home-based therapy and those treated conventionally. Of the 118 infants who were admitted for treatment of NAS, 38 (32%) were managed at home. Infants receiving home-based detoxification had shorter hospital stays (mean 19 days vs. 39 days), with no increase in total duration of treatment (mean 36 days vs. 41 days), and were more likely to be breastfeeding on discharge from hospital care (45% vs. 22%). In selected infants, home-based detoxification is associated with reduced hospital stays and increased rates of breastfeeding, without prolonging therapy. Safety of the infants remains paramount, which precludes many from entering such a programme. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  3. An overactivated ATR/CHK1 pathway is responsible for the prolonged G2 accumulation in irradiated AT cells

    NASA Technical Reports Server (NTRS)

    Wang, Xiang; Khadpe, Jay; Hu, Baocheng; Iliakis, George; Wang, Ya

    2003-01-01

    Induction of checkpoint responses in G1, S, and G2 phases of the cell cycle after exposure of cells to ionizing radiation (IR) is essential for maintaining genomic integrity. Ataxia telangiectasia mutated (ATM) plays a key role in initiating this response in all three phases of the cell cycle. However, cells lacking functional ATM exhibit a prolonged G2 arrest after IR, suggesting regulation by an ATM-independent checkpoint response. The mechanism for this ataxia telangiectasia (AT)-independent G2-checkpoint response remains unknown. We report here that the G2 checkpoint in irradiated human AT cells derives from an overactivation of the ATR/CHK1 pathway. Chk1 small interfering RNA abolishes the IR-induced prolonged G2 checkpoint and radiosensitizes AT cells to killing. These results link the activation of ATR/CHK1 with the prolonged G2 arrest in AT cells and show that activation of this G2 checkpoint contributes to the survival of AT cells.

  4. TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: PHYSIOLOGICAL REACTIVITY TO TRAUMA IMAGERY AS AN OBJECTIVE MEASURE OF TREATMENT RESPONSE.

    PubMed

    Wangelin, Bethany C; Tuerk, Peter W

    2015-12-01

    Physiological reactivity to trauma-related cues is a primary symptom of PTSD and can be assessed objectively using script-driven imagery paradigms. However, subjective self-reported symptom measures are the most common outcome indices utilized in PTSD treatment trials and clinic settings. We examined physiological reactivity during a short trauma imagery task as an objective index of response to PTSD treatment, optimized for use in routine clinical care settings. Participants were 35 male combat veterans receiving prolonged exposure (PE) therapy in a Veterans Affairs outpatient clinic. In addition to traditional subjective self-reported and clinician-rated symptom measures, patients also completed a script-driven imagery task in which heart rate (HR) and skin conductance (SC) were recorded at three assessment points across treatment. We examined changes in subjective symptom measures and objective trauma-specific physiological reactivity over the course of PE, and investigated the association between pretreatment physiological reactivity and treatment response. Patients who completed PE showed significantly diminished HR and SC reactivity to trauma imagery across therapy. Additionally, individuals showing greater trauma-specific HR reactivity at pretreatment showed greater reductions in subjectively reported PTSD symptoms at posttreatment. Findings support the utility of physiological reactivity during trauma imagery as an objective outcome measure that has the potential to be incorporated into evidence-based PTSD treatment in routine clinical settings, or prospective studies related to the individualization of care at pretreatment. © 2015 Wiley Periodicals, Inc.

  5. Noise exposure in convertible automobiles.

    PubMed

    Mikulec, A A; Lukens, S B; Jackson, L E; Deyoung, M N

    2011-02-01

    To quantify the noise exposure received while driving a convertible automobile with the top open, compared with the top closed. Five different convertible automobiles were driven, with the top both closed and open, and noise levels measured. The cars were tested at speeds of 88.5, 104.6 and 120.7 km/h. When driving with the convertible top open, the mean noise exposure ranged from 85.3 dB at 88.5 km/h to 89.9 dB at 120.7 km/h. At the tested speeds, noise exposure increased by an average of 12.4-14.6 dB after opening the convertible top. Driving convertible automobiles at speeds exceeding 88.5 km/h, with the top open, may result in noise exposure levels exceeding recommended limits, especially when driving with the convertible top open for prolonged periods.

  6. Prolonged pain and disability are common after rib fractures.

    PubMed

    Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

    2013-05-01

    The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Bisphenol A exposure and cardiac electrical conduction in excised rat hearts.

    PubMed

    Posnack, Nikki Gillum; Jaimes, Rafael; Asfour, Huda; Swift, Luther M; Wengrowski, Anastasia M; Sarvazyan, Narine; Kay, Matthew W

    2014-04-01

    Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. The goal of our study was to measure the effect of BPA (0.1-100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1-100 μM BPA), prolonged action potential duration (1-100 μM BPA), and delayed atrioventricular conduction (10-100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA's effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations.

  8. Prolonged delirium misdiagnosed as a mood disorder.

    PubMed

    Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

    2017-01-01

    Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

  9. Clinical factors and incidence of prolonged fever in neurosurgical patients.

    PubMed

    Wang, Zhuo; Shen, Meifen; Qiao, Meizhen; Zhang, Haiyin; Tang, Zaixiang

    2017-02-01

    To describe the incidence of prolonged fever in patients admitted to the neurosurgery department, and the corresponding risk indicators. Prolonged fever was defined as a temperature higher than 38·3°C lasting more than five days. Prolonged fever is a common phenomenon and could lead to worsened outcomes in specific patient groups, especially for those with brain injury. However, the studies on prolonged fever in neurosurgical patients are limited and insufficient. A retrospective observational study. Retrospective data were collected from 1 January 2014 to 31 December 2014, at the neurosurgical department of a large teaching hospital. We performed univariate and multivariate analyses to identify independent indicators for prolonged fever vs. short-term fever. Among 2845 patients, prolonged fever occurred in 466 (16%). The older patients were associated with longer duration of mechanical ventilation and hospital stay. It predominantly occurred in patients with subarachnoid haemorrhage (SAH) and traumatic brain injury. Patients receiving antibiotic treatment tended to manifest prolonged fever more frequently. Multivariate analysis revealed that the use of antibiotics, central venous catheter and prolonged mechanical ventilation were independent risk predictors for prolonged fever. Patients diagnosed with brain tumour seemed to be not associated with prolonged fever. Prolonged fever is the common complication in neurosurgical patients. The risks of prolonged fever in patients are attributed to antibiotic therapy, use of central venous catheter and prolonged mechanical ventilation. Indicators of prolonged fever are helpful for better identification of high-risk patients and fever control. A better reveal on the epidemiology and predictable factors of prolonged fever in neurosurgical patients will provide a better understanding on those patients who are most at risk, and therefore contribute to fever control and better outcome. © 2016 John Wiley & Sons Ltd.

  10. Physiological responses of mules on prolonged exposure to high altitude (3 650 m)

    NASA Astrophysics Data System (ADS)

    Riar, S. S.; Shankar Bhat, K.; Sen Gupta, J.

    1982-06-01

    Eight healthy male animals were inducted and kept for 2 1/2 years at 3 650 m altitude and subjected to normal work schedules. Physiological measurements viz. heart rate, blood pressure, minute ventilation, oxygen consumption, respiration rate, hemoglobin, packed cell haematocrit volume and eosinophil count were made on these animals at periodic intervals. On acute induction to an altitude of 3 650 m these animals demonstrated a sudden increase in tidal volume, a decrease in Rf and no change in VE, suggesting a decreased dead space/tidal volume ratio at altitude. However, all these changes stabilised within 3 weeks but on prolongation of stay, the physical state of these animals was adversely affected. The respiratory adjustments occurring on return to sea level appear to be a response to thermal stress. The initial increase in heart rate and blood pressure stabilised by the 2nd week.

  11. QT interval prolongation associated with sibutramine treatment

    PubMed Central

    Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

    2006-01-01

    Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

  12. Background radiation: natural and man-made.

    PubMed

    Thorne, M C

    2003-03-01

    A brief overview and comparison is given of dose rates arising from natural background radiation and the fallout from atmospheric testing of nuclear weapons. Although there are considerable spatial variations in exposure to natural background radiation, it is useful to give estimates of worldwide average overall exposures from the various components of that background. Cosmic-ray secondaries of low linear energy transfer (LET), mainly muons and photons, deliver about 280 microSv a(-1). Cosmic-ray neutrons deliver about another 100 microSv a(-1). These low- and high-LET exposures are relatively uniform to the whole body. The effective dose rate from cosmogenic radionuclides is dominated by the contribution of 12 microSv a(-1) from 14C. This is due to relatively uniform irradiation of all organs and tissues from low-energy beta particles. Primordial radionuclides and their progeny (principally the 238U and 232Th series, and 40K) contribute about 480 microSv a(-1) of effective dose by external irradiation. This is relatively uniform photon irradiation of the whole body. Internally incorporated 40K contributes a further 165 microSv a(-1) of effective dose in adults, mainly from beta particles, but with a significant gamma component. Equivalent doses from 40K are somewhat higher in muscle than other soft tissues, but the distinction is less than a factor of three. Uranium and thorium series radionuclides give rise to an average effective dose rate of around 120 microSv a(-1). This includes a major alpha particle component, and exposures of radiosensitive tissues in lung, liver, kidney and the skeleton are recognised as important contributors to effective dose. Overall, these various sources give a worldwide average effective dose rate of about 1160 microSv a(-1). Exposure to 222Rn, 220Rn and their short-lived progeny has to be considered separately. This is very variable both within and between countries. For 222Rn and its progeny, a worldwide average effective dose

  13. A potential mechanism for the impairment of nitric oxide formation caused by prolonged oral exposure to arsenate in rabbits.

    PubMed

    Pi, Jingbo; Horiguchi, Satomi; Sun, Yang; Nikaido, Masatoshi; Shimojo, Nobuhiro; Hayashi, Toshio; Yamauchi, Hiroshi; Itoh, Ken; Yamamoto, Masayuki; Sun, Guifan; Waalkes, Michael P; Kumagai, Yoshito

    2003-07-01

    change occurred in cardiac L-arginine levels. These results suggest that prolonged exposure of rabbits to oral arsenate may impair the bioavailability of BH(4) in endothelial cells and, as a consequence, disrupt the balance between NO and O2(.-) produced from endothelial NOS, such that enhanced free radicals are produced at the expense of NO.

  14. Dioxin Exposure Initiative

    EPA Pesticide Factsheets

    The Dioxin Exposure Initiative (DEI) is no longer active. This page contains a summary of the dioxin exposure initiative with illustrations, contact and background information.Originally supported by scientist Matthew Lorber, who retired in Mar 2017.

  15. Screening for Older Emergency Department Inpatients at Risk of Prolonged Hospital Stay: The Brief Geriatric Assessment Tool

    PubMed Central

    Launay, Cyrille P.; de Decker, Laure; Kabeshova, Anastasiia; Annweiler, Cédric; Beauchet, Olivier

    2014-01-01

    Background The aims of this study were 1) to confirm that combinations of brief geriatric assessment (BGA) items were significant risk factors for prolonged LHS among geriatric patients hospitalized in acute care medical units after their admission to the emergency department (ED); and 2) to determine whether these combinations of BGA items could be used as a prognostic tool of prolonged LHS. Methods Based on a prospective observational cohort design, 1254 inpatients (mean age ± standard deviation, 84.9±5.9 years; 59.3% female) recruited upon their admission to ED and discharged in acute care medical units of Angers University Hospital, France, were selected in this study. At baseline assessment, a BGA was performed and included the following 6 items: age ≥85years, male gender, polypharmacy (i.e., ≥5 drugs per day), use of home-help services, history of falls in previous 6 months and temporal disorientation (i.e., inability to give the month and/or year). The LHS in acute care medical units was prospectively calculated in number of days using the hospital registry. Results Area under receiver operating characteristic (ROC) curves of prolonged LHS of different combinations of BGA items ranged from 0.50 to 0.57. Cox regression models revealed that combinations defining a high risk of prolonged LHS, identified from ROC curves, were significant risk factors for prolonged LHS (hazard ratio >1.16 with P>0.010). Kaplan-Meier distributions of discharge showed that inpatients classified in high-risk group of prolonged LHS were discharged later than those in low-risk group (P<0.003). Prognostic value for prolonged LHS of all combinations was poor with sensitivity under 77%, a high variation of specificity (from 26.6 to 97.4) and a low likelihood ratio of positive test under 5.6. Conclusion Combinations of 6-item BGA tool were significant risk factors for prolonged LHS but their prognostic value was poor in the studied sample of older inpatients. PMID:25333271

  16. Mechanisms of Change in Cognitive Processing Therapy and Prolonged Exposure Therapy for PTSD: Preliminary Evidence for the Differential Effects of Hopelessness and Habituation

    PubMed Central

    Resick, Patricia A.

    2013-01-01

    The present study examined two potential mechanisms of change, hopelessness cognitions and habituation, in a randomized controlled trial of cognitive processing therapy (CPT) and prolonged exposure therapy (PE) for posttraumatic stress disorder (PTSD). Participants were 171 adult women with a current primary diagnosis of sexual assault related PTSD. The potential mechanisms were examined by evaluating the intraindividual change in hopelessness within the course of both treatments and subjective units distress (SUDS) ratings (a proxy for habituation) within the course of PE. The effects of intraindividual change in the proposed mechanisms were then examined on within-treatment changes in PTSD symptoms. Findings indicated that the participants assigned to the CPT treatment had significantly greater pre-post reductions in hopelessness than those assigned to PE and that the changes in hopelessness predicted changes in PTSD symptoms (R2 = .24). Intraindividual changes in SUDS ratings for participants in the PE treatment condition also predicted changes in PTSD symptoms and did so independently of the effect of changes in hopelessness. Future research should examine these mechanisms using more intensive methods of data collection that would permit the demonstration of temporality of change. PMID:24363472

  17. Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: A prospective study that accounts for weight change.

    PubMed

    Lee, Duk-Hee; Lind, P Monica; Jacobs, David R; Salihovic, Samira; van Bavel, Bert; Lind, Lars

    2016-01-01

    Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case-control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change. Plasma concentrations of 3 OC pesticides (p,p'-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases. The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides <25th percentile, adjusted hazard ratios (HRs) in those with 25th-<75th and ≥75th percentiles were 3.5 (95% confidence interval: 1.5-8.5) and 3.2 (1.1-7.6), respectively (Ptrend=0.04). Among 506 subjects who maintained or gained body weight, adjusted HRs were 6.9 and 11.6 (1.4-92.6) among the elderly in the 25th-<75th and ≥75th percentiles compared to <25th percentile (Ptrend<0.01). This prospective study demonstrates that background exposure to OC pesticides are linked to the risk of developing cognitive impairment in elderly. The role of the chronic exposure to low dose OC pesticides in the development of dementia should be further evaluated in other populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u.ac.jp; Yoshimi, Masaki; Kadota, Yoshito

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered amore » dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.« less

  19. A multi-site single blind clinical study to compare the effects of prolonged exposure, eye movement desensitization and reprocessing and waiting list on patients with a current diagnosis of psychosis and co morbid post traumatic stress disorder: study protocol for the randomized controlled trial Treating Trauma in Psychosis.

    PubMed

    de Bont, Paul A J M; van den Berg, David P G; van der Vleugel, Berber M; de Roos, Carlijn; Mulder, Cornelis L; Becker, Eni S; de Jongh, Ad; van der Gaag, Mark; van Minnen, Agnes

    2013-05-23

    Trauma contributes to psychosis and in psychotic disorders post-traumatic stress disorder (PTSD) is often a comorbid disorder. A problem is that PTSD is underdiagnosed and undertreated in people with psychotic disorders. This study's primary goal is to examine the efficacy and safety of prolonged exposure and eye movement desensitization and reprocessing (EMDR) for PTSD in patients with both psychotic disorders and PTSD, as compared to a waiting list. Secondly, the effects of both treatments are determined on (a) symptoms of psychosis, in particular verbal hallucinations, (b) depression and social performance, and (c) economic costs. Thirdly, goals concern links between trauma exposure and psychotic symptomatology and the prevalence of exposure to traumatic events, and of PTSD. Fourthly predictors, moderators, and mediators for treatment success will be explored. These include cognitions and experiences concerning treatment harm, credibility and burden in both participants and therapists. A short PTSD-screener assesses the possible presence of PTSD in adult patients (21- to 65- years old) with psychotic disorders, while the Clinician Administered PTSD Scale interview will be used for the diagnosis of current PTSD. The M.I.N.I. Plus interview will be used for diagnosing lifetime psychotic disorders and mood disorders with psychotic features. The purpose is to include consenting participants (N = 240) in a multi-site single blind randomized clinical trial. Patients will be allocated to one of three treatment conditions (N = 80 each): prolonged exposure or EMDR (both consisting of eight weekly sessions of 90 minutes each) or a six-month waiting list. All participants are subjected to blind assessments at pre-treatment, two months post treatment, and six months post treatment. In addition, participants in the experimental conditions will have assessments at mid treatment and at 12 months follow-up. The results from the post treatment measurement can be considered

  20. Inflammation and airway hyperresponsiveness after chlorine exposure are prolonged by Nrf2 deficiency in mice.

    PubMed

    Ano, Satoshi; Panariti, Alice; Allard, Benoit; O'Sullivan, Michael; McGovern, Toby K; Hamamoto, Yoichiro; Ishii, Yukio; Yamamoto, Masayuki; Powell, William S; Martin, James G

    2017-01-01

    Chlorine gas (Cl 2 ) is a potent oxidant and trigger of irritant induced asthma. We explored NF-E2-related factor 2 (Nrf2)-dependent mechanisms in the asthmatic response to Cl 2 , using Nrf2-deficient mice, buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis and sulforaphane (SFN), a phytochemical regulator of Nrf2. Airway inflammation and airway hyperresponsiveness (AHR) were assessed 24 and 48h after a 5-min nose-only exposure to 100ppm Cl 2 of Nrf2-deficient and wild type Balb/C mice treated with BSO or SFN. Animals were anesthetized, paralyzed and mechanically ventilated (FlexiVent™) and challenged with aerosolized methacholine. Bronchoalveolar lavage (BAL) was performed and lung tissues were harvested for assessment of gene expression. Cl 2 exposure induced a robust AHR and an intense neutrophilic inflammation that, although similar in Nrf2-deficient mice and wild-type mice at 24h after Cl 2 exposure, were significantly greater at 48h post exposure in Nrf2-deficient mice. Lung GSH and mRNA for Nrf2-dependent phase II enzymes (NQO-1 and GPX2) were significantly lower in Nrf2-deficient than wild-type mice after Cl 2 exposure. BSO reduced GSH levels and promoted Cl 2 -induced airway inflammation in wild-type mice, but not in Nrf2-deficient mice, whereas SFN suppressed Cl 2 -induced airway inflammation in wild-type but not in Nrf2-deficient mice. AHR was not affected by either BSO or SFN at 48h post Cl 2 exposure. Nrf2-dependent phase II enzymes play a role in the resolution of airway inflammation and AHR after Cl 2 exposure. Moderate deficiency of GSH affects the magnitude of acute inflammation but not AHR. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

    PubMed Central

    Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

    2010-01-01

    Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

  2. The Need for Self-Report Data in the Assessment of Stuttering Therapy Efficacy: Repetitions and Prolongations of Speech. The Stuttering Syndrome

    ERIC Educational Resources Information Center

    Guntupalli, Vijaya K.; Kalinowski, Joseph; Saltuklaroglu, Tim

    2006-01-01

    Background: Bloodstein reviewed hundreds of studies that investigated the efficacy of therapeutic protocols for ameliorating the stuttering syndrome. Surprisingly, almost all were effective in significantly reducing overtly perceptible behaviours such as repetitions and prolongations of speech sounds. These results seem highly improbable…

  3. Prolonged second stage of labor is associated with low Apgar score.

    PubMed

    Altman, Maria; Sandström, Anna; Petersson, Gunnar; Frisell, Thomas; Cnattingius, Sven; Stephansson, Olof

    2015-11-01

    There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 min. All nulliparous women (n = 32,796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 min <7 and <4. We found that the overall rates of 5 min Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 h from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 min generally increased with length of second stage of labor: 1 to <2 h: OR 1.78 (95% CI 1.19-2.66); 2 to <3 h: OR 1.66 (1.05-2.62); 3 to <4 h: OR 2.08 (1.29-3.35); and ≥4 h: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 min Apgar score.

  4. Modeling background radiation in Southern Nevada

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haber, Daniel A.; Burnley, Pamela C.; Adcock, Christopher T.

    Aerial gamma ray surveys are an important tool for national security, scientific, and industrial interests in determining locations of both anthropogenic and natural sources of radioactivity. There is a relationship between radioactivity and geology and in the past this relationship has been used to predict geology from an aerial survey. The purpose of this project is to develop a method to predict the radiologic exposure rate of the geologic materials by creating a high resolution background model. The intention is for this method to be used in an emergency response scenario where the background radiation envi-ronment is unknown. Two studymore » areas in Southern Nevada have been modeled using geologic data, images from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), geochemical data, and pre-existing low resolution aerial surveys from the National Uranium Resource Evaluation (NURE) Survey. Using these data, geospatial areas that are homogenous in terms of K, U, and Th, referred to as background radiation units, are defined and the gamma ray exposure rate is predicted. The prediction is compared to data collected via detailed aerial survey by the Department of Energy's Remote Sensing Lab - Nellis, allowing for the refinement of the technique. By using geologic units to define radiation background units of exposed bedrock and ASTER visualizations to subdivide and define radiation background units within alluvium, successful models have been produced for Government Wash, north of Lake Mead, and for the western shore of Lake Mohave, east of Searchlight, NV.« less

  5. Modeling background radiation in Southern Nevada

    DOE PAGES

    Haber, Daniel A.; Burnley, Pamela C.; Adcock, Christopher T.; ...

    2017-02-06

    Aerial gamma ray surveys are an important tool for national security, scientific, and industrial interests in determining locations of both anthropogenic and natural sources of radioactivity. There is a relationship between radioactivity and geology and in the past this relationship has been used to predict geology from an aerial survey. The purpose of this project is to develop a method to predict the radiologic exposure rate of the geologic materials by creating a high resolution background model. The intention is for this method to be used in an emergency response scenario where the background radiation envi-ronment is unknown. Two studymore » areas in Southern Nevada have been modeled using geologic data, images from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), geochemical data, and pre-existing low resolution aerial surveys from the National Uranium Resource Evaluation (NURE) Survey. Using these data, geospatial areas that are homogenous in terms of K, U, and Th, referred to as background radiation units, are defined and the gamma ray exposure rate is predicted. The prediction is compared to data collected via detailed aerial survey by the Department of Energy's Remote Sensing Lab - Nellis, allowing for the refinement of the technique. By using geologic units to define radiation background units of exposed bedrock and ASTER visualizations to subdivide and define radiation background units within alluvium, successful models have been produced for Government Wash, north of Lake Mead, and for the western shore of Lake Mohave, east of Searchlight, NV.« less

  6. Heart Rate Variability Frequency Domain Alterations among Healthy Nurses Exposed to Prolonged Work Stress.

    PubMed

    Borchini, Rossana; Veronesi, Giovanni; Bonzini, Matteo; Gianfagna, Francesco; Dashi, Oriana; Ferrario, Marco Mario

    2018-01-11

    The deregulation of the autonomic nervous system assessed through the heart rate variability (HRV) analysis is a promising pathway linking work stress and cardiovascular diseases. We aim to investigate the associations between HRV High Frequency (HF) and Low Frequency (LF) powers and work stress in a sample of 36 healthy nurses. Perceived work stress was assessed twice one year apart, using the Job Content and Effort Reward Imbalance questionnaires. This allows to classify nurses in three exposure groups: "prolonged high stress" (PHS), "recent high stress" (RHS) and "stable low stress" (SLS). A 24-h ECG monitoring was later performed during a working day (WD) and a subsequent resting day (RD). Statistically significantly lower ( p < 0.02) HF and LF means were found in PHS and RHS nurses during the working periods. In the subsequent resting periods, HF means showed increases over time in the RHS (beta = +0.41, p < 0.05), but not in PHS nurses. LF means did not show any substantial increases in the resting periods, in the PHS group with geometric means lower when compared to SLS, in the non-working and resting periods. Our study evidences that both prolonged and recent perceived high work stress were associated with a reduction of HF and LF powers during work. In addition, prolonged stress was associated with a lack of recovery during not-working and resting periods.

  7. Does UTI cause prolonged jaundice in otherwise well infants?

    PubMed

    Chowdhury, Tanzila; Kisat, Hamudi; Tullus, Kjell

    2015-07-01

    The symptoms of urinary tract infections in infants are very non-specific and have historically included prolonged hyperbilirubinaemia. We studied the results of routine urine samples in 319 infants with prolonged jaundice. Convincing findings of UTI was not found in any of these children even if one of them was treated with antibiotics after four consecutive urine cultures with different bacteria. A urine culture might thus not be an appropriate investigation in a child with prolonged jaundice without any other symptoms of UTI. • The symptoms of UTI in infancy are very non-specific. • Old studies suggest that prolonged hyperbilirubinaemia is one such symptom; more modern studies give more conflicting results. What is New: • Our study could not confirm that children with prolonged jaundice have an increased risk of UTI. • Routine urine testing is thus not needed in otherwise healthy infants with prolonged jaundice.

  8. Assessing the outcomes of prolonged cessation-induction and aid-to-cessation trials: floating prolonged abstinence.

    PubMed

    Aveyard, Paul; Wang, Dechao; Connock, Martin; Fry-Smith, Anne; Barton, Pelham; Moore, David

    2009-05-01

    A Society for Research on Nicotine and Tobacco working group recommended outcome measures for cessation-induction trials and aid-to-cessation trials. Cessation-induction trials aim to motivate unwilling quitters to make a quit attempt. Aid-to-cessation trials give either medication or behavioral interventions to increase the rate at which willing quitters succeed in their attempts. Nicotine-assisted reduction programs combine features of both types of interventions by giving nicotine replacement to unwilling quitters. Treatment can be prolonged more than a year, quit attempts can occur and succeed early or late in the program, and renewed quit attempts are an inherent part of the program. Conventional outcome measures are tied to a fixed but arbitrary point in follow-up and cannot capture the true outcome: Prolonged cessation anchored to the point at which a person makes a successful quit attempt. We propose that the outcome should be counted from the successful quit attempt that began during the treatment period and continues for a defined period, ideally 6 months. In particular, if a trial compared a short reduction program with a long reduction program, it would not be possible to obtain an unbiased assessment of the outcome of such a trial using a measure tied to a fixed point in follow-up. Floating prolonged abstinence could provide such an assessment and is suitable for either prolonged cessation-induction trial or combined cessation-induction and aid-to-cessation trials.

  9. The U.N. Population Fund: Background and the U.S. Funding Debate

    DTIC Science & Technology

    2008-01-11

    programs to promote expanded opportunities for the education of women and girls, to end gender discrimination and violence against women, and to...UNFPA annual reports, 1997-2006. CRS-5 5 Obstetric fistula occurs from prolonged child labor, particularly when labor lasts two days or more. When a...Problems in the World: Obstetric Fistula: Background Information and Responses, by Tiaji Salaam-Blyther. UNFPA Program Priorities. Currently, UNFPA

  10. Prolonged whole body immersion in cold water: hormonal and metabolic changes.

    PubMed

    Smith, D J; Deuster, P A; Ryan, C J; Doubt, T J

    1990-03-01

    To characterize metabolic and hormonal responses during prolonged whole body immersion, 16 divers wearing dry suits completed four immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 meters of sea water. One immersion began in the AM (1000 h) and one began in the PM (2200 h) to evaluate diurnal variations. Venous blood samples were obtained before and after completion of each immersion. Cortisol and ACTH levels demonstrated diurnal variation, with larger increases occurring after PM immersions. A greater than three-fold postimmersion increase occurred in norepinephrine (NE). There were significant increases in triiodothyronine (T3) uptake and epinephrine, but no change in T3, thyroxine, thyrotrophic hormone, and dopamine. Postimmersion free fatty acid levels increased 409% from preimmersion levels; glucose levels declined, and lactate increased significantly. Only changes in NE correlated significantly with changes in rectal temperature. In summary, when subjects are immersed in cold water for prolonged periods, with a slow rate of body cooling afforded by thermal protection and intermittent exercise, hormonal and metabolic changes occur that are similar in direction and magnitude to short-duration unprotected exposures. Except for cortisol and ACTH, none of the other measured variables exhibited diurnal alterations.

  11. Prolonged ictal aphasia: a diagnosis to consider.

    PubMed

    Herskovitz, Moshe; Schiller, Yitzhak

    2012-11-01

    Aphasia is a common symptom encountered by clinical neurologists. It is usually caused by strokes or lesions involving language regions of the brain, yet prolonged aphasia is rarely the sole manifestation of a simple partial status epilepticus. We report six patients, who suffered from prolonged ictal aphasia. All but one patient had a structural lesion in the left hemisphere, only three suffered from clinical seizures during or shortly prior to the aphasic episode. All patients had ictal patterns on the electroencephalogram (EEG), four of whom had periodic lateralized epileptiform discharges, and five showed frequent recurrent electrographic seizures during the aphasic state. The aphasia lasted several days in all patients, and it resolved after administration of antiepileptic drug treatment. In conclusion, prolonged ictal aphasia is a rare but important treatable cause of aphasia. Surface EEG recordings should be obtained in all patients with unexplained prolonged aphasia to diagnose this rare but treatable entity. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  12. Prolonged length of stay in hospitalized internal medicine patients.

    PubMed

    Barba, Raquel; Marco, Javier; Canora, Jesús; Plaza, Susana; Juncos, Sara Nistal; Hinojosa, Juan; Bailon, Manuel Mendez; Zapatero, Antonio

    2015-12-01

    Targeting patients with prolonged hospitalizations may represent an effective strategy for reducing average hospital length of stay (LOS). We sought to characterize predictors of prolonged hospitalization among internal medicine patients in an effort to guide future improvement efforts. We conducted a retrospective cohort study using administrative data of internal medicine patients from all hospitals of the Spanish Public Health Service between January 1st, 2005 and December 31st, 2013. Multivariable logistic regression was performed to assess the association between sociodemographic and clinical variables and prolonged LOS, defined as >30days. Of 5,275,139 discharges, 166,470 (3.2%) had a prolonged LOS. Prolonged hospitalizations accounted for 17.4% of total inpatient days and contributed 0.5days to an average LOS of 9.8days during the study period. Prolonged hospitalizations were associated with younger age (odds ratio [OR]: 0.97 per 10-year increase in age, 95% confidence interval [CI]: 0.96-0.98) and male gender (OR 0.88 IC95% 0.87-0.89). Compared to patients without prolonged LOS, prolonged LOS patients were more likely to require a palliative care consult (OR: 2.48, 95% CI: 2.39-2.58), surgery (OR: 6.9 95% CI: 6.8-7.0); and be discharged to a post-acute-care facility (OR: 2.91, 95% CI: 2.86-2.95). Prolonged hospitalizations in a small proportion of patients were an important contributor to overall LOS and particularly affected complex hospital stays who were not discharged home. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  13. Issue Paper on Metal Exposure Assessment

    EPA Pesticide Factsheets

    This paper explores the best approaches for characterizing exposure pathways and routes, estimating the most relevant exposure concentrations, linking exposure to dose, and coping with natural or background concentrations.

  14. Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; Shibasaki, M.; Wilson, T. E.; Cui, J.; Levine, B. D.

    2003-01-01

    Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

  15. A study of the effects of long-term exposure to fuels and fluids on the behavior of advanced composite materials

    NASA Technical Reports Server (NTRS)

    Tanimoto, E. Y.

    1981-01-01

    The periodic testing and evaluation of graphite/epoxy and Kevlar/epoxy material systems after subjecting test specimens to prolonged exposure to several laboratory-controlled environments deemed typical of normal aircraft operations is discussed. It is noted that specimen immersion in water or water-based fluids resulted in the greatest effect on the mechanical properties tested. Also, the environmental fluids showed a tendency to affect Kevlar/epoxy systems at an earlier exposure period than the graphite/epoxy systems. Results also indicate mechanical property strength retention generally being lower for the Kevlar/epoxy systems when compared to the corresponding graphite/epoxy systems in similar environments, after prolonged exposure.

  16. Prolonged QRS Widening After Aripiprazole Overdose.

    PubMed

    Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

    2018-05-05

    Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

  17. A detailed description of the short-term musculoskeletal and cognitive effects of prolonged standing for office computer work.

    PubMed

    Baker, Richelle; Coenen, Pieter; Howie, Erin; Lee, Jeremy; Williamson, Ann; Straker, Leon

    2018-07-01

    Due to concerns about excessive sedentary exposure for office workers, alternate work positions such as standing are being trialled. However, prolonged standing may have health and productivity impacts, which this study assessed. Twenty adult participants undertook two hours of laboratory-based standing computer work to investigate changes in discomfort and cognitive function, along with muscle fatigue, movement, lower limb swelling and mental state. Over time, discomfort increased in all body areas (total body IRR [95% confidence interval]: 1.47[1.36-1.59]). Sustained attention reaction time (β = 18.25[8.00-28.51]) deteriorated, while creative problem solving improved (β = 0.89[0.29-1.49]). There was no change in erector spinae, rectus femoris, biceps femoris or tibialis anterior muscle fatigue; low back angle changed towards less  lordosis, pelvis movement increased, lower limb swelling increased and mental state decreased. Body discomfort was positively correlated with mental state. The observed changes suggest replacing office work sitting with standing should be done with caution. Practitioner Summary: Standing is being used to replace sitting by office workers; however, there are health risks associated with prolonged standing. In a laboratory study involving 2 h prolonged standing discomfort increased (all body areas), reaction time and mental state deteriorated while creative problem-solving improved. Prolonged standing should be undertaken with caution.

  18. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cros, C., E-mail: caroline.cros@hotmail.co.uk; Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com; Moors, J.

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau ofmore » each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects

  19. Occupational Solvent Exposure and Brain Function: An fMRI Study

    PubMed Central

    Carpenter, David M.; Eaves, Emily L.; Ng, Johnny; Ganeshalingam, Nimalya; Weisel, Clifford; Qian, Hua; Lange, Gudrun; Fiedler, Nancy L.

    2011-01-01

    Background: Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown. Objectives: We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers. Methods: Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure. Results: Solvent-exposed workers’ performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices—areas serving working memory function and attention—was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers. Conclusions: This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology

  20. Aging leads to prolonged duration of inflammation-induced depression-like behavior caused by Bacillus Calmette-Guérin.

    PubMed

    Kelley, Keith W; O'Connor, Jason C; Lawson, Marcus A; Dantzer, Robert; Rodriguez-Zas, Sandra L; McCusker, Robert H

    2013-08-01

    Geriatric depression is a costly health issue, but little is known about its physiological underpinnings. Systemic inflammation sensitizes the innate immune system of aged animals and humans, but it is unknown if chronic, low-grade infections affect the duration of depressive-like behaviors. In this report, we infected adult (4-6 months) and aged (20-24 months) Balb/c mice with an attenuated strain of Mycobacterium bovis, Bacillus Calmette-Guérin (BCG), to induce a chronic infection. We then measured depression-like behaviors that have construct, face and predictive validity for human inflammation-associated clinical depression. Exposure to BCG caused acute sickness responses in both adult and aged mice. However, sickness behavior was prolonged in aged mice, as assessed by both locomotor and rearing activity. Two measures of depression-like behavior, which were tests involving sucrose preference and tail suspension, both showed that adult mice displayed depression-like behaviors at one day and seven days after exposure to BCG. However, aged mice continued to express both of these depression-like behaviors at three weeks following infection. Infection with BCG caused an increase in tryptophan catabolism, as evidenced by a significant rise in the plasma kynurenine/tryptophan ratio that peaked at 7 days post-infection. In aged mice, greater tryptophan catabolism persisted longer and remained elevated at 21 days post-infection. This finding is consistent with the prolonged duration of depression-like behaviors in aged mice. These are the first data using a chronic infection model to establish that recovery from inflammation-induced depression-like behavior and tryptophan catabolism are prolonged in aged animals. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Adapting to warmer climate through prolonged maize grain filling period in the US Midwest

    NASA Astrophysics Data System (ADS)

    Zhu, P.; Zhuang, Q.; Jin, Z.

    2017-12-01

    Climate warming is expected to negatively impact the US food productivity. How to adapt to the future warmer environment and meet the rising food requirement becomes unprecedented urgent. Continuous satellite observational data provides an opportunity to examine the historic responses of crop plants to climate variation. Here 16 years crop growing phases information across US Midwest is generated based on satellite observations. We found a prolonged grain-filling period during 2000-2015, which could partly explain the increasing trend in Midwest maize yield. This longer grain-filling period might be resulted from the adoption of longer maturity group varieties or more resistant varieties to temperature variation. Other management practice changes like advance in planting date could be also an effective way of adapting future warmer climate through lowering the possibility of exposure to heat and drought stresses. If the progress in breeding technology enables the maize grain-filling period to prolong with the current rate, the maize grain filling length could be longer and maize yield in Midwest could adapt to future climate despite of the warming.

  2. Lactate and pH evaluation in exhausted humans with prolonged TASER X26 exposure or continued exertion.

    PubMed

    Ho, Jeffrey D; Dawes, Donald M; Cole, Jon B; Hottinger, Julie C; Overton, Kenneth G; Miner, James R

    2009-09-10

    Safety concerns about TASER Conducted Electrical Weapon (CEW) use and media reports of deaths after exposure have been expressed. CEWs are sometimes used on exhausted subjects to end resistance. The alternative is often a continued struggle. It is unclear if CEW use is metabolically different than allowing a continued struggle. We sought to determine if CEW exposure on exhausted humans caused worsening acidosis when compared with continued exertion. This was a prospective study of human volunteers recruited during a CEW training course. Volunteers were from several different occupations and represented a wide range of ages and body mass index characteristics. Medical histories, baseline pH and lactate values were obtained. Patients were assigned to one of four groups: 2 control groups consisting of Exertion only and CEW Exposure only, and the 2 experimental groups that were Exertion plus CEW Exposure and Exertion plus additional Exertion. Blood sampling occurred after Exertion and after any CEW exposure. This was repeated every 2-min until 20 min after protocol completion. Descriptive statistics were used to compare the four groups. The experimental groups and the control groups were compared individually at each time point using Wilcoxon rank sum tests. Lactate and pH association was assessed using multiple linear regression. Forty subjects were enrolled. There were no median pH or lactate differences between CEW Exposure groups at baseline, or between Exertion protocol groups immediately after completion. The CEW Exposure only group had higher pH and lower lactate values at all time points after exposure than the Exertion only group. After completing the Exertion protocol, there was no difference in the pH or lactate values between the continued Exertion group and the CEW Exposure group at any time points. Subjects who had CEW Exposure only had higher pH and lower lactate values than subjects who completed the Exertion protocol only. CEW exposure does not appear

  3. Prior exposure to corticosterone markedly enhances and prolongs the neuroinflammatory response to systemic challenge with LPS

    PubMed Central

    Michalovicz, Lindsay T.; Miller, Julie V.; Castranova, Vincent; Miller, Diane B.

    2018-01-01

    Systemic exposure to the inflammagen and bacterial endotoxin lipopolysaccharide (LPS) has been widely used to evaluate inflammation and sickness behavior. While many inflammatory conditions occur in the periphery, it is well established that peripheral inflammation can affect the brain. Neuroinflammation, the elaboration of proinflammatory mediators in the CNS, commonly is associated with behavioral symptoms (e.g., lethargy, anhedonia, anorexia, depression, etc.) termed sickness behavior. Stressors have been shown to interact with and alter neuroinflammatory responses and associated behaviors. Here, we examined the effects of the stress hormone, corticosterone (CORT), as a stressor mimic, on neuroinflammation induced with a single injection (2mg/kg, s.c.) or inhalation exposure (7.5 μg/m3) of LPS or polyinosinic:polycytidylic acid (PIC; 12mg/kg, i.p.) in adult male C57BL/6J mice. CORT was given in the drinking water (200 mg/L) for 1 week or every other week for 90 days followed by LPS. Proinflammatory cytokine expression (TNFα, IL-6, CCL2, IL-1β, LIF, and OSM) was measured by qPCR. The activation of the neuroinflammation downstream signaling activator, STAT3, was assessed by immunoblot of pSTAT3Tyr705. The presence of astrogliosis was assessed by immunoassay of GFAP. Acute exposure to LPS caused brain-wide neuroinflammation without producing astrogliosis; exposure to CORT for 1 week caused marked exacerbation of the LPS-induced neuroinflammation. This neuroinflammatory “priming” by CORT was so pronounced that sub-neuroinflammatory exposures by inhalation instigated neuroinflammation when paired with prior CORT exposure. This effect also was extended to another common inflammagen, PIC (a viral mimic). Furthermore, a single week of CORT exposure maintained the potential for priming for 30 days, while intermittent exposure to CORT for up to 90 days synergistically primed the LPS-induced neuroinflammatory response. These findings highlight the possibility for an

  4. Carotid Baroreflex Function During Prolonged Exercise

    NASA Technical Reports Server (NTRS)

    Raven, P. B.

    1999-01-01

    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  5. Mobile phone signal exposure triggers a hormesis-like effect in Atm+/+ and Atm-/- mouse embryonic fibroblasts.

    PubMed

    Sun, Chuan; Wei, Xiaoxia; Fei, Yue; Su, Liling; Zhao, Xinyuan; Chen, Guangdi; Xu, Zhengping

    2016-11-18

    Radiofrequency electromagnetic fields (RF-EMFs) have been classified by the International Agency for Research on Cancer as possible carcinogens to humans; however, this conclusion is based on limited epidemiological findings and lacks solid support from experimental studies. In particular, there are no consistent data regarding the genotoxicity of RF-EMFs. Ataxia telangiectasia mutated (ATM) is recognised as a chief guardian of genomic stability. To address the debate on whether RF-EMFs are genotoxic, we compared the effects of 1,800 MHz RF-EMF exposure on genomic DNA in mouse embryonic fibroblasts (MEFs) with proficient (Atm +/+ ) or deficient (Atm -/- ) ATM. In Atm +/+ MEFs, RF-EMF exposure for 1 h at an average special absorption rate of 4.0 W/kg induced significant DNA single-strand breaks (SSBs) and activated the SSB repair mechanism. This effect reduced the DNA damage to less than that of the background level after 36 hours of exposure. In the Atm -/- MEFs, the same RF-EMF exposure for 12 h induced both SSBs and double-strand breaks and activated the two repair processes, which also reduced the DNA damage to less than the control level after prolonged exposure. The observed phenomenon is similar to the hormesis of a toxic substance at a low dose. To the best of our knowledge, this study is the first to report a hormesis-like effect of an RF-EMF.

  6. Responses of older men with and without chronic obstructive pulmonary disease to prolonged ozone exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gong, H. Jr.; Shamoo, D.A.; Anderson, K.R.

    1997-01-01

    We tested responses to ozone (O{sub 3}) under simulated {open_quotes}worst-case{close_quotes} ambient exposure conditions. Subjects included 9 men who had severe chronic obstructive pulmonary disease (COPD) with subnormal carbon monoxide diffusing capacity (i.e., an emphysemic component) and 10 age-matched healthy men. Each subject was exposed to 0.24 ppm O{sub 3} and to clean air (control) in an environmentally controlled chamber at 24{degrees}C and 40% relative humidity. Exposures were randomized, they occurred 1 wk apart, and they lasted 4 h. During each half-hour interval, light exercise occurred (e.e., average ventilation 20 l/mm) for 15 min. during both control and O{sub 3} exposures,more » group mean symptom intensity and specific airway resistance (SRaw) increased, whereas forced expiratory performance decreased. The healthy subgroup`s mean arterial oxygen saturation (SaO{sub 2}) rose slightly, and the COPD subgroup`s mean SaO{sub 2} declined slightly, during exercise. Group mean forced expiratory volume in 1 s (FEV{sub 1.0}) declined significantly in O{sub 3} exposures, compared with controls (p {approx}.01). Mean excess FEV{sub 1.0} loss after 4 h in O{sub 3} (relative to control) was 8% of the preexposure value in the COPD subgroup, compared with 3% in the healthy subgroup (p > .05 [nonsignificant]). Overall FEV{sub 1.0} loss during O{sub 3} exposures, including exercise effects, averaged 19% in the COPD subgroup, compared with 2% in the healthy subgroup (p < .001). Symptoms, SRaw, and SaO{sub 2} responses, as well as healthy subjects` postexposure bronchial reactivity, differed little between O{sub 3}-exposed and control subjects. We therefore concluded that in older men with or without severe COPD, O{sub 3} causes lung dysfunction under {open_quotes}worst-case{close_quotes} ambient exposure conditions, despite older subjects` comparative unresponsiveness to O{sub 3}. 30 refs., 2 figs., 2 tabs.« less

  7. Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury.

    PubMed

    Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

    2016-10-14

    To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.

  8. Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury

    PubMed Central

    Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

    2016-01-01

    AIM To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. METHODS Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage. PMID:27784962

  9. Visual Function Changes after Laser Exposure.

    DTIC Science & Technology

    1984-04-01

    degeneration induced by prolonged exposure to flourescent light. Using the ERG as a criterion response Noell et al (5) showed that the damage action...without photoreceptors. Exp Neurol 1972;34:446-454 15. Bennett 11H, Dyer RF, Dunn JD. Light-induced retinal degeneration : effect upon light-dark...20. Lemmon V, Anderson VV. Behavioral effects of retinal degeneration . Exp Neurol 1979;63:35-49 21. Wright A, Sperling HG. Psychophysical biochemical

  10. Pulmonary fibrosis and exposure to steel welding fume.

    PubMed

    Cosgrove, M P

    2015-12-01

    Arc welders who have been exposed to high concentrations of steel welding fume for prolonged periods of time may develop pulmonary fibrosis but the nature of the fibrotic changes has been debated over the last 80 years without any clear international consensus. To characterize the nature of the pulmonary fibrosis that develops in response to steel welding fume exposure and to provide a working hypothesis that would explain the findings of the existing research, to provide a platform for future research and to inform future occupational and clinical management of welders with pulmonary effects from welding fume. Review of the world literature on pulmonary fibrosis and welding of steel in all languages using PubMed, with further secondary search of references in the articles found in the primary search. Google and Reference Manager were used as further confirmatory search tools. Only case series and case reports were found but these provided consistent evidence that the consequence of exposure to steel welding fume at high levels for a prolonged period of time is a type of pulmonary fibrosis similar to, and possibly the same as, respiratory bronchiolitis which eventually develops into desquamative interstitial pneumonia with ongoing exposure. Steel welding fume may cause an occupational respiratory bronchiolitis which may develop into de squamative interstitial pneumonia with ongoing exposure. This concept may explain the difficulties in interpreting the wider literature on welding fume and lung function at lower exposures and may also explain the increased risk of lung cancer in welders. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Prolonged breast-feeding and mortality up to two years post-partum among HIV-positive women in Zambia

    PubMed Central

    Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Semrau, Katherine; Vwalika, Cheswa; Tsai, Wei-Yann; Aldrovandi, Grace M.; Thea, Donald M.

    2005-01-01

    Background A previously reported association between prolonged lactation and maternal mortality has generated concern that breast-feeding may be detrimental for HIV-positive women. Methods As part of a trial conducted in Lusaka, Zambia, 653 HIV-positive women were randomly assigned either to a counseling program that encouraged abrupt cessation of breast-feeding at 4 months (group A) or to a program that encouraged prolonged breast-feeding for the duration of the woman’s own informed choice (group B). We examined whether mortality up to 2 years post-partum increased with breast-feeding for a longer duration. Results There was no difference in mortality 12 months after delivery between 326 HIV-positive women randomly assigned to short breast-feeding [group A: 4.93%; 95% confidence interval (CI), 2.42–7.46] versus 327 women assigned to long breast-feeding (group B: 4.89%; 95% CI, 2.38–7.40). Analysis based on actual practice, rather than random assignment, also demonstrated no increased mortality due to breast-feeding. Conclusions Although HIV-related mortality was high in this cohort of untreated HIV-positive women, prolonged lactation was not associated with increased mortality. PMID:16184038

  12. Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp; Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp; Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp

    2014-07-01

    Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min formore » 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.« less

  13. Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.

    PubMed

    Casey, Michael J; Wen, Xuerong; Kayler, Liise K; Aiyer, Ravi; Scornik, Juan C; Meier-Kriesche, Herwig-Ulf

    2014-08-15

    When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal. We retrospectively examined subjects transplanted at a single center between July 1, 1999 and December 1, 2009 with a non-death-related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only. We found 102 subjects with non-death-related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups, respectively (P=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% CI [1.37-24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group. These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.

  14. Development and Validation of a Simplified Renal Replacement Therapy Suitable for Prolonged Field Care in a Porcine (Sus scrofa) Model of Acute Kidney Injury

    DTIC Science & Technology

    2018-03-01

    of a Simplified Renal Replacement Therapy Suitable for Prolonged Field Care in a Porcine (Sus scrofa) Model of Acute Kidney Injury. PRINCIPAL...and methods, results - include tables/figures, and conclusions/applications.) Objectives/Background: Acute kidney injury (AKI) is a serious

  15. Olfactory cortical adaptation facilitates detection of odors against background.

    PubMed

    Kadohisa, Mikiko; Wilson, Donald A

    2006-03-01

    Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output.

  16. Increased beta-adrenergic responsiveness induced by 14 days exposure to simulated microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Polet, J. L.; Engelke, K. A.; Hoffler, G. W.; Lane, L. D.; Blomqvist, C. G.

    1995-01-01

    Increased sensitivity of end-organ responses to neuroendocrine stimuli as a result of prolonged exposure to the relative inactivity of microgravity has recently been hypothesized. This notion is based on the inverse relationship between circulating norepinephrine and beta-adrenoreceptor sensitivity. The beta-adrenoreceptor activity is reduced in individuals who have elevated plasma norepinephrine as a result of regular exposure to upright posture and physical exercise. In contrast, adrenoreceptor hypersensitivity has been reported in patients with dysautonomias in which circulating catecholamines are absent or reduced. Taken together, these studies and the observation that circulating plasma norepinephrine has been reduced during spaceflight and in groundbased simulations of microgravity prompt the suggestion that adrenoreceptor hypersensitivity may be a consequence of the adaptation to spaceflight. We conducted an experiment designed to measure cardiovascular responses to adrenoreceptor agonists in human subjects before and after prolonged exposure to 6 deg head-down tilt (HDT) to test the hypothesis that adaptation to microgravity increases adrenoreceptor responsiveness, and that this adaptation is associated with reduced levels of circulating norepinephrine.

  17. Tolerance and Withdrawal From Prolonged Opioid Use in Critically Ill Children

    PubMed Central

    Anand, Kanwaljeet J. S.; Willson, Douglas F.; Berger, John; Harrison, Rick; Meert, Kathleen L.; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J. L.; Prodhan, Parthak; Dean, J. Michael; Nicholson, Carol

    2012-01-01

    OBJECTIVE After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS Relevant manuscripts published in the English language were searched in Medline by using search terms “opioid,” “opiate,” “sedation,” “analgesia,” “child,” “infant-newborn,” “tolerance,” “dependency,” “withdrawal,” “analgesic,” “receptor,” and “individual opioid drugs.” Clinical and preclinical studies were reviewed for data synthesis. RESULTS Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal. PMID:20403936

  18. Prolonged partial cardiopulmonary bypass in rats.

    PubMed

    Alexander, B; Al Ani, H R

    1983-07-01

    Membrane oxygenators have been shown to be atraumatic during cardiopulmonary bypass. A novel design for a membrane tubing oxygenator originated in this laboratory was used for prolonged partial supportive cardiopulmonary bypass in lambs and displayed excellent biocompatability characteristics. This was miniaturized, to result in a prime volume of 12 ml, in order to investigate the feasibility of prolonged partial supportive cardiopulmonary bypass in rats. The performance of this miniaturized circuit over perfusion periods up to 6 hr is described, with particular reference to hematological changes.

  19. A Systematic Review of the Use of Buccal Midazolam in the Emergency Treatment of Prolonged Seizures in Adults with Learning Disabilities

    ERIC Educational Resources Information Center

    Marshall, Thomas

    2007-01-01

    Background: Buccal midazolam is widely used in children for the emergency treatment of epilepsy, and these children are graduating into adult learning disability services. Aims: The aim of this paper was to appraise the evidence for buccal midazolam as a treatment for prolonged seizures in adults with learning disabilities. Method: A literature…

  20. Aircraft and background noise annoyance effects

    NASA Technical Reports Server (NTRS)

    Willshire, K. F.

    1984-01-01

    To investigate annoyance of multiple noise sources, two experiments were conducted. The first experiment, which used 48 subjects, was designed to establish annoyance-noise level functions for three community noise sources presented individually: jet aircraft flyovers, air conditioner, and traffic. The second experiment, which used 216 subjects, investigated the effects of background noise on aircraft annoyance as a function of noise level and spectrum shape; and the differences between overall, aircraft, and background noise annoyance. In both experiments, rated annoyance was the dependent measure. Results indicate that the slope of the linear relationship between annoyance and noise level for traffic is significantly different from that of flyover and air conditioner noise and that further research was justified to determine the influence of the two background noises on overall, aircraft, and background noise annoyance (e.g., experiment two). In experiment two, total noise exposure, signal-to-noise ratio, and background source type were found to have effects on all three types of annoyance. Thus, both signal-to-noise ratio, and the background source must be considered when trying to determine community response to combined noise sources.

  1. Venetoclax does not prolong the QT interval in patients with hematological malignancies: an exposure-response analysis.

    PubMed

    Freise, Kevin J; Dunbar, Martin; Jones, Aksana K; Hoffman, David; Enschede, Sari L Heitner; Wong, Shekman; Salem, Ahmed Hamed

    2016-10-01

    Venetoclax (ABT-199/GDC-0199) is a selective first-in-class B cell lymphoma-2 inhibitor being developed for the treatment of hematological malignancies. The aim of this study was to determine the potential of venetoclax to prolong the corrected QT (QTc) interval and to evaluate the relationship between systemic venetoclax concentration and QTc interval. The study population included 176 male and female patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 105) or non-Hodgkin's lymphoma (n = 71) enrolled in a phase 1 safety, pharmacokinetic, and efficacy study. Electrocardiograms were collected in triplicate at time-matched points (2, 4, 6, and 8 h) prior to the first venetoclax administration and after repeated venetoclax administration to achieve steady state conditions. Venetoclax doses ranged from 100 to 1200 mg daily. Plasma venetoclax samples were collected after steady state electrocardiogram measurements. The mean and upper bound of the 2-sided 90 % confidence interval (CI) QTc change from baseline were <5 and <10 ms, respectively, at all time points and doses (<400, 400, and >400 mg). Three subjects had single QTc values >500 ms and/or ΔQTc > 60 ms. The effect of venetoclax concentration on both ΔQTc and QTc was not statistically significant (P > 0.05). At the mean maximum concentrations achieved with therapeutic (400 mg) and supra-therapeutic (1200 mg) venetoclax doses, the estimated drug effects on QTc were 0.137 (90 % CI [-1.01 to 1.28]) and 0.263 (90 % CI [-1.92 to 2.45]) ms, respectively. Venetoclax does not prolong QTc interval even at supra-therapeutic doses, and there is no relationship between venetoclax concentrations and QTc interval.

  2. Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress.

    PubMed

    Zou, Yingxin; Liu, Yuxiang; Ruan, Minghua; Feng, Xu; Wang, Jiachun; Chu, Zhiyong; Zhang, Zesheng

    2015-10-01

    This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process.

  3. Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress

    PubMed Central

    ZOU, YINGXIN; LIU, YUXIANG; RUAN, MINGHUA; FENG, XU; WANG, JIACHUN; CHU, ZHIYONG; ZHANG, ZESHENG

    2015-01-01

    This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process. PMID:26239097

  4. Prolongation structures of nonlinear evolution equations

    NASA Technical Reports Server (NTRS)

    Wahlquist, H. D.; Estabrook, F. B.

    1975-01-01

    A technique is developed for systematically deriving a 'prolongation structure' - a set of interrelated potentials and pseudopotentials - for nonlinear partial differential equations in two independent variables. When this is applied to the Korteweg-de Vries equation, a new infinite set of conserved quantities is obtained. Known solution techniques are shown to result from the discovery of such a structure: related partial differential equations for the potential functions, linear 'inverse scattering' equations for auxiliary functions, Backlund transformations. Generalizations of these techniques will result from the use of irreducible matrix representations of the prolongation structure.

  5. Adaptation to prolonged bedrest in man: A compendium of research. [bibliographies on clinical medicine and human pathology

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Greenleaf, C. J.; Vanderveer, D.; Dorchak, K. J.

    1976-01-01

    A compilation of major studies that describe the clinical observations and elucidate the physiological mechanisms of the adaptive process of man undergoing prolonged bed rest is presented. Additional studies are included that provide background information in the form of reviews or summaries of the process. Wherever possible a detailed annotation is provided under the subheadings: (1) purpose, (2) procedure and methods, (3) results, and (4) conclusions. Additional references are provided in a selected bibliography.

  6. Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

    PubMed

    Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

    2017-10-03

    The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

  7. Yield of prolonged wireless pH monitoring in achalasia patients successfully treated with pneumatic dilation

    PubMed Central

    Franchina, Marianna; Elvevi, Alessandra; Pugliese, Delia; Tenca, Andrea; Conte, Dario; Penagini, Roberto

    2016-01-01

    Background Gastro-oesophageal reflux disease (GORD) is a long-term complication of achalasia treatments. The aim of our study was to evaluate the yield of prolonged wireless pH monitoring in patients with successfully treated achalasia and its influence on proton pump inhibitor (PPI) use. Methods Twenty-five patients with achalasia who underwent prolonged wireless pH monitoring after a successful treatment with pneumatic dilation were enrolled. pH variables were analysed in the first 24 hours of monitoring to determine if tracings were indicative of GORD; the same variables were analysed in the following 24-hour period in order to obtain a worst-day diagnosis of GORD. PPI therapy before and after the test was recorded. Results Five out of 25 patients had GORD diagnosis during the first day of monitoring and four of them had oesophagitis at endoscopy. During the following days of monitoring four more patients had a diagnosis of GORD. Out of the 25 patients, PPIs were started after the test in six asymptomatic GORD-positive ones, whereas prescription of PPIs was stopped without detrimental effect on symptoms in three GORD-negative patients. Conclusions Prolonged wireless pH monitoring is a useful test to be added to endoscopy in order to evaluate GORD and to optimise antisecretory treatment in successfully treated achalasia patients. PMID:29026592

  8. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    PubMed Central

    Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

    2016-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

  9. The Shift of ERG B-Wave Induced by Hours' Dark Exposure in Rodents

    PubMed Central

    Li, Dake; Fang, Qi; Yu, Hongbo

    2016-01-01

    Purpose Dark adaptation can induce a rapid functional shift in the retina, and after that, the retinal function is believed to remain stable during the continuous dark exposure. However, we found that electroretinograms (ERG) b-waves gradually shifted during 24 hours’ dark exposure in rodents. Detailed experiments were designed to explore this non-classical dark adaptation. Methods In vivo ERG recording in adult and developing rodents after light manipulations. Results We revealed a five-fold decrease in ERG b-waves in adult rats that were dark exposed for 24 hours. The ERG b-waves significantly increased within the first hour’s dark exposure, but after that decreased continuously and finally attained steady state after 1 day’s dark exposure. After 3 repetitive, 10 minutes’ light exposure, the dark exposed rats fully recovered. This recovery effect was eye-specific, and light exposure to one eye could not restore the ERGs in the non-exposed eye. The prolonged dark exposure-induced functional shift was also reflected in the down-regulation on the amplitude of intensity-ERG response curve, but the dynamic range of the responsive light intensity remained largely stable. Furthermore, the ERG b-wave shifts occurred in and beyond classical critical period, and in both rats and mice. Importantly, when ERG b-wave greatly shifted, the amplitude of ERG a-wave did not change significantly after the prolonged dark exposure. Conclusions This rapid age-independent ERG change demonstrates a generally existing functional shift in the retina, which is at the entry level of visual system. PMID:27517462

  10. The Shift of ERG B-Wave Induced by Hours' Dark Exposure in Rodents.

    PubMed

    Li, Dake; Fang, Qi; Yu, Hongbo

    2016-01-01

    Dark adaptation can induce a rapid functional shift in the retina, and after that, the retinal function is believed to remain stable during the continuous dark exposure. However, we found that electroretinograms (ERG) b-waves gradually shifted during 24 hours' dark exposure in rodents. Detailed experiments were designed to explore this non-classical dark adaptation. In vivo ERG recording in adult and developing rodents after light manipulations. We revealed a five-fold decrease in ERG b-waves in adult rats that were dark exposed for 24 hours. The ERG b-waves significantly increased within the first hour's dark exposure, but after that decreased continuously and finally attained steady state after 1 day's dark exposure. After 3 repetitive, 10 minutes' light exposure, the dark exposed rats fully recovered. This recovery effect was eye-specific, and light exposure to one eye could not restore the ERGs in the non-exposed eye. The prolonged dark exposure-induced functional shift was also reflected in the down-regulation on the amplitude of intensity-ERG response curve, but the dynamic range of the responsive light intensity remained largely stable. Furthermore, the ERG b-wave shifts occurred in and beyond classical critical period, and in both rats and mice. Importantly, when ERG b-wave greatly shifted, the amplitude of ERG a-wave did not change significantly after the prolonged dark exposure. This rapid age-independent ERG change demonstrates a generally existing functional shift in the retina, which is at the entry level of visual system.

  11. Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

    PubMed Central

    Keller, David M.; Low, David A.; Davis, Scott L.; Hastings, Jeff

    2011-01-01

    Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ∼34°C and skin surface cooling ∼12–15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ∼30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals. PMID:21454746

  12. Mechanisms of zolpidem-induced long QT syndrome: acute inhibition of recombinant hERG K+ channels and action potential prolongation in human cardiomyocytes derived from induced pluripotent stem cells

    PubMed Central

    Jehle, J; Ficker, E; Wan, X; Deschenes, I; Kisselbach, J; Wiedmann, F; Staudacher, I; Schmidt, C; Schweizer, PA; Becker, R; Katus, HA; Thomas, D

    2013-01-01

    Background and Purpose Zolpidem, a short-acting hypnotic drug prescribed to treat insomnia, has been clinically associated with acquired long QT syndrome (LQTS) and torsade de pointes (TdP) tachyarrhythmia. LQTS is primarily attributed to reduction of cardiac human ether-a-go-go-related gene (hERG)/IKr currents. We hypothesized that zolpidem prolongs the cardiac action potential through inhibition of hERG K+ channels. Experimental Approach Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record hERG currents from Xenopus oocytes and from HEK 293 cells. In addition, hERG protein trafficking was evaluated in HEK 293 cells by Western blot analysis, and action potential duration (APD) was assessed in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. Key Results Zolpidem caused acute hERG channel blockade in oocytes (IC50 = 61.5 μM) and in HEK 293 cells (IC50 = 65.5 μM). Mutation of residues Y652 and F656 attenuated hERG inhibition, suggesting drug binding to a receptor site inside the channel pore. Channels were blocked in open and inactivated states in a voltage- and frequency-independent manner. Zolpidem accelerated hERG channel inactivation but did not affect I–V relationships of steady-state activation and inactivation. In contrast to the majority of hERG inhibitors, hERG cell surface trafficking was not impaired by zolpidem. Finally, acute zolpidem exposure resulted in APD prolongation in hiPSC-derived cardiomyocytes. Conclusions and Implications Zolpidem inhibits cardiac hERG K+ channels. Despite a relatively low affinity of zolpidem to hERG channels, APD prolongation may lead to acquired LQTS and TdP in cases of reduced repolarization reserve or zolpidem overdose. PMID:23061993

  13. Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

    PubMed

    Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno

    2012-01-01

    Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.

  14. Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice.

    PubMed

    Horiguchi, Hyogo; Oguma, Etsuko

    2016-12-01

    Acute exposure to cadmium (Cd), a toxic heavy metal, causes systemic inflammation characterized by neutrophilia. To elucidate the mechanism of neutrophilia induced by Cd, we investigated the induction of granulocyte colony-stimulating factor (G-CSF), which regulates neutrophil production, in mice with acute Cd toxicity, and compared it with mice injected with lipopolysaccharide (LPS) as an inducer of general inflammatory responses. We injected BALB/c mice with Cd at 2.5 mg/kg i.p. or LPS at 0.5 mg/kg i.p. and sampled the peripheral blood and organs at time points up to 24 h. In Cd-treated mice, the peripheral neutrophil count increased steadily up to 24 h, whereas LPS-treated mice showed a more rapid increase with a peak at 12 h. The serum G-CSF level increased gradually to reach a plateau at 12-18 h in Cd-treated mice, but LPS-treated mice showed a marked increase, reaching a peak at 2-3 h. A gradual elevation of G-CSF mRNA expression up to 24 h was detected by real-time PCR in the livers of Cd-treated mice, but in LPS-treated mice its highest expression was observed in the liver with a rapid increase at 2 h. By in situ hybridization using G-CSF RNA probes, hepatic Kupffer cells were identified as G-CSF-producing cells in the liver. These results indicated that Cd has a characteristic effect of delayed induction of G-CSF in the liver, causing systemic inflammation accompanied by prolonged neutrophilia.

  15. A review of ropinirole prolonged release in Parkinson’s disease

    PubMed Central

    Nashatizadeh, Muhammad M; Lyons, Kelly E; Pahwa, Rajesh

    2009-01-01

    Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson’s disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily “off” time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD. PMID:19503779

  16. Prolonged Effects of Acute Stress on Decision-Making under Risk: A Human Psychophysiological Study

    PubMed Central

    Yamakawa, Kaori; Ohira, Hideki; Matsunaga, Masahiro; Isowa, Tokiko

    2016-01-01

    This study investigates the prolonged effects of physiological responses induced by acute stress on risk-taking in decision-making. Participants were divided into a Stress group (N = 14) and a Control group (N = 12). The Trier Social Stress Test was administered as an acute stressor, and reading was administered as a control task; thereafter, participants performed a decision-making task in which they needed to choose a sure option or a gamble option in Gain and Loss frame trials 2 h after (non-) exposure to the stressor. Increased cortisol, adrenaline, heart rate (HR), and subjective stress levels validated acute stress manipulation. Stressed participants made fewer risky choices only in the Gain domain, whereas no effect of stress was shown in the Loss domain. Deceleration of HR reflecting attention was greater for Gains compared with Losses only in the Stress group. Risk avoidance was determined by increased levels of cortisol caused by acute stress. These results suggest that processes regarding glucocorticoid might be involved in the prolonged effects of acute stress on the evaluation of risks and the monitoring of outcomes in decision-making. PMID:27679566

  17. Granularity of the Diffuse Background Observed

    NASA Technical Reports Server (NTRS)

    Gruber, D. E.; MacDonald, D.; Rothschild, R. E.; Boldt, E.; Mushotzky, R. F.; Fabian, A. C.

    1995-01-01

    First results are reported from a program for measuring the field-to-field fluctuation level of the cosmic diffuse background by using differences between the two background positions of each deep exposure with the High Energy X-ray Timing Experiment (HEXTE) instrument on the Remote X Ray Timing Explorer (RXTE). With 8 million live seconds accumulated to date a fluctuation level on the 15-25 keV band is observed which is consistent with extrapolations from the High Energy Astrophysical Observatory-1 (HEAO-1) measurements. Positive results are expected eventually at higher energies. Models of (active galactic nuclei) AGN origin will eventually be constrained by this program.

  18. EXPOSURE METHODOLOGIES AND SYSTEMS FOR LONG-TERM CHEMICAL CARCINOGENICITY STUDIES WITH SMALL FISH SPECIES

    EPA Science Inventory

    Testing waterborne chemical carcinogens in fish models requires accurate, reliable, and reproducible exposures. Because carcinogenesis is a chronic toxicological process and is often associated with prolonged latency periods, systems must accommodate lengthy in-life test periods ...

  19. Predictive Associations of Music, Anxiety, and Sedative Exposure on Mechanical Ventilation Weaning Trials

    PubMed Central

    Hetland, Breanna; Lindquist, Ruth; Weinert, Craig R.; Peden-McAlpine, Cynthia; Savik, Kay; Chlan, Linda

    2017-01-01

    Background Weaning from mechanical ventilation requires increased respiratory effort, which can heighten anxiety and later prolong the need for mechanical ventilation. Objectives To examine the predictive associations of music intervention, anxiety, sedative exposure, and patients’ characteristics on time to initiation and duration of weaning trials of patients receiving mechanical ventilation. Methods A descriptive, correlational design was used for a secondary analysis of data from a randomized trial. Music listening was defined as self-initiated, patient-directed music via headphones. Anxiety was measured daily with a visual analog scale. Sedative exposure was operationalized as a daily sedation intensity score and a sedative dose frequency. Analyses consisted of descriptive statistics, graphing, survival analysis, Cox proportional hazards regression, and linear regression. Results Of 307 patients, 52% were women and 86% were white. Mean age was 59.3 (SD, 14.4) years, mean Acute Physiology and Chronic Health Evaluation III score was 62.9 (SD, 21.6), mean duration of ventilatory support was 8 (range, 1–52) days, and mean stay in the intensive care unit was 18 (range, 2–71) days. Music listening, anxiety levels, and sedative exposure did not influence time to initial weaning trial or duration of trials. Clinical factors of illness severity, days of weaning trials, and tracheostomy placement influenced weaning patterns in this sample. Conclusions Prospective studies of music intervention and other psychophysiological factors during weaning from mechanical ventilation are needed to better understand factors that promote successful weaning. PMID:28461543

  20. A review on natural background radiation

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Gholami, Mehrdad; Setayandeh, Samaneh

    2013-01-01

    The world is naturally radioactive and approximately 82% of human-absorbed radiation doses, which are out of control, arise from natural sources such as cosmic, terrestrial, and exposure from inhalation or intake radiation sources. In recent years, several international studies have been carried out, which have reported different values regarding the effect of background radiation on human health. Gamma radiation emitted from natural sources (background radiation) is largely due to primordial radionuclides, mainly 232Th and 238U series, and their decay products, as well as 40K, which exist at trace levels in the earth's crust. Their concentrations in soil, sands, and rocks depend on the local geology of each region in the world. Naturally occurring radioactive materials generally contain terrestrial-origin radionuclides, left over since the creation of the earth. In addition, the existence of some springs and quarries increases the dose rate of background radiation in some regions that are known as high level background radiation regions. The type of building materials used in houses can also affect the dose rate of background radiations. The present review article was carried out to consider all of the natural radiations, including cosmic, terrestrial, and food radiation. PMID:24223380

  1. Fluorescent light exposure incites acute and prolonged immune responses in zebrafish (Danio rerio) skin.

    PubMed

    Gonzalez, Trevor J; Lu, Yuan; Boswell, Mikki; Boswell, William; Medrano, Geraldo; Walter, Sean; Ellis, Samuel; Savage, Markita; Varga, Zoltan M; Lawrence, Christian; Sanders, George; Walter, Ronald B

    2018-06-01

    Artificial light produces an emission spectrum that is considerably different than the solar spectrum. Artificial light has been shown to affect various behavior and physiological processes in vertebrates. However, there exists a paucity of data regarding the molecular genetic effects of artificial light exposure. Previous studies showed that one of the commonly used fluorescent light source (FL; 4100K or "cool white") can affect signaling pathways related to maintenance of circadian rhythm, cell cycle progression, chromosome segregation, and DNA repair/recombination in the skin of male Xiphophorus maculatus. These observations raise questions concerning the kinetics of the FL induced gene expression response, and which biological functions become modulated at various times after light exposure. To address these questions, we exposed zebrafish to 4100K FL and utilized RNA-Seq to assess gene expression changes in skin at various times (1 to 12h) after FL exposure. We found 4100K FL incites a robust early (1-2h) transcriptional response, followed by a more protracted late response (i.e., 4-12h). The early transcriptional response involves genes associated with cell migration/infiltration and cell proliferation as part of an overall increase in immune function and inflammation. The protracted late transcriptional response occurs within gene sets predicted to maintain and perpetuate the inflammatory response, as well as suppression of lipid, xenobiotic, and melatonin metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Chemical exposure in occupational settings and related health risks: a neglected area of research in Pakistan.

    PubMed

    Kamal, Atif; Malik, Riffat Naseem; Fatima, Noreen; Rashid, Audil

    2012-07-01

    In Pakistan a huge number of workers is routinely exposed to various types of chemical contaminants but there is a dearth of information as to the impact of these agents, due to a lack of a routine surveillance system and proper reporting. Prolonged and sometimes acute occupational exposures to varied organic chemicals may result in numerous health related problems. Studies from all over the world have shown adverse health outcomes of chemicals that are commonly used in various occupations. Such chemical exposures are not just confined to the workplace, but the residents surrounding industrial sites also face significant health risks due to indirect chemical exposure. Occupational exposure is a multidimensional risk factor that varies from one occupation to another, and is associated with health decline in workers. Common determinants of workplace hazards include improper, or lack of use of self-protective equipment, active and passive exposure to cigarette smoke as well as the socio-demographic and economic background of workers. There may be more than one cause of occupational stress and psychophysical disturbance among workers such as workload, lower salaries, and lack of social and medical facilities; indeed, their general health is poor. Therefore, in Pakistan, it is particularly important to focus on these issues and set rules and regulations to create occupational hazard awareness among workers, which will promote health safety at work places. If priorities are given to the correct use of self-protective equipment, adopting proper hygiene at the workplace and to avoid smoking, occupational exposures and consequent health risks may be minimized significantly. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Why are we prolonging QT interval monitoring?

    PubMed

    Barrett, Trina

    2015-01-01

    At present, monitoring of the QT interval (QTI) is not a standard practice in the medical intensive care unit setting, where many drugs that prolong the QTI are administered. This literature review looked at the current research for evidence-based standards to support QTI monitoring of patients with risk factors for QTI prolongation, which can result in life-threatening arrhythmias such as torsade de pointes. The objective of this article is to establish the existence of evidence-based standards for monitoring of the QTI and to raise awareness in the nursing profession of the need for such monitoring among patients who are at high risk for prolonged QTI. To determine whether published standards for QTI monitoring exist, a search was conducted of the bibliographic databases CINAHL, EBSCOhost, Medline, PubMed, Google Scholar, and the Cochrane Library for the years 2013 and 2014. Also, a survey was conducted to determine whether practice standards for QTI monitoring are being implemented at 4 major hospitals in the Memphis area, including a level 1 trauma center. The database search established the existence of published guidelines that support the need for QTI monitoring. Results of the hospital survey indicated that direct care nurses were not aware of the need to identify high-risk patients, drugs with the potential to prolong QTI that were being administered to their patients, or evidence-based standards for QTI monitoring. Review of the research literature underscored the need for QTI monitoring among high-risk patients, that is, those with genetic conditions that predispose them to QTI prolongation, those with existing cardiac conditions being treated with antiarrhythmic medications, or those who are prescribed any new medication classified as high risk on the basis of clinical research. This need is especially crucial in intensive care unit settings, where many antiarrhythmic medications are administered.

  4. A pilot and feasibility randomised controlled study of Prolonged Exposure Treatment and supportive counselling for post-traumatic stress disorder in adolescents: a third world, task-shifting, community-based sample.

    PubMed

    Rossouw, Jaco; Yadin, Elna; Alexander, Debra; Mbanga, Irene; Jacobs, Tracy; Seedat, Soraya

    2016-11-17

    There is a dearth of empirical evidence on the effectiveness of pharmacological and nonpharmacological treatments for adolescents with post-traumatic stress disorder (PTSD) in developing country settings. The primary aim of this study was to demonstrate that Prolonged Exposure Treatment for Adolescents (PE-A) and supportive counselling (SC) are implementable by nurses in a South African context. A secondary aim was to perform a preliminary analysis of the effectiveness of registered nurses delivering either PE-A or SC treatment to adolescents with PTSD. It is hypothesised that PE-A will be superior to SC in terms of improvements in PTSD symptoms and depression. A pilot, single-blind, randomised clinical trial of 11 adolescents with PTSD. Nurses previously naïve to Prolonged Exposure (PE) Treatment and SC provided these treatments at the adolescents' high schools. Data collection lasted from March 2013 to October 2014. Participants received twelve 60-90-min sessions of PE (n = 6) or SC (n = 5). All outcomes were assessed before treatment, at mid-treatment, immediately after treatment completion and at 12-month follow-up. The primary outcome, PTSD symptom severity, was assessed with the Child PTSD Symptom Scale-Interview (CPSS-I) (range, 0-51; higher scores indicate greater severity). The secondary outcome, depression severity, was assessed with the Beck Depression Inventory (BDI) (range, 0-41; higher scores indicate greater severity). Data were analysed as intention to treat. During treatment, participants in both the PE-A and SC treatment arms experienced significant improvement on the CPSS-I as well as on the BDI. There was a significant difference between the PE-A and SC groups in maintaining PTSD and depression at the 12-month post-treatment assessment, with the participants in the PE-A group maintaining their gains both on PTSD and depression measures. The treatment was adequately implemented by the nurses and well-tolerated by the participants

  5. Differential effect of exposure-based therapy and cognitive therapy on post-traumatic stress disorder symptom clusters: A randomized controlled trial.

    PubMed

    Horesh, Danny; Qian, Meng; Freedman, Sara; Shalev, Arieh

    2017-06-01

    A question remains regarding differential effects of exposure-based versus non-exposure-based therapies on specific post-traumatic stress disorder (PTSD) symptom clusters. Traumatized emergency room patients were randomized to receive prolonged exposure (PE) or cognitive therapy (CT) without exposure. PE/CT had no differential effect on individual symptom clusters, and change in total PTSD score remained significant even after controlling for the reductions in all three symptom clusters. In addition, baseline levels of PTSD avoidance/intrusion/hyperarousal did not moderate the effects of PE and CT on total PTSD symptom scores. Taken together, these findings challenge the notion that PE and CT are specifically, and differentially, useful in treating one particular PTSD symptom cluster. Despite their different theoretical backgrounds and techniques, the notion that PE and CT (without exposure) target different PTSD symptoms was not confirmed in this study. Thus, both interventions may in fact be equally effective for treating intrusion, avoidance and hyperarousal symptoms. Baseline levels of avoidance, intrusion and hyperarousal may not be good a priori indicators for PTSD treatment selection. The effect of PE and CT on PTSD as a whole does not seem to depend on a reduction in any specific symptom cluster. These findings indicate that exposure and non-exposure interventions may lead to similar results in terms of reductions in specific PTSD symptoms. It is quite possible that individual PTSD clusters may respond to therapy in an inter-related fashion, with one cluster affecting the other. © 2016 The British Psychological Society.

  6. Effects of prolonged exposure of lettuce seeds to HZE particles on orbital stations

    NASA Astrophysics Data System (ADS)

    Nevzgodina, L. V.; Maksimova, E. N.; Kaminskaya, E. V.

    In a study of the biological effects of cosmic HZE particles, lettuce (Lactuca sativa) seeds were flown on the orbital stations Salyut 6 and 7 for varying periods of time (from 40 to 457 days). The dependence of the biological damage on flight duration, physical parameters and the fact of passage of an HZE particle through the seed was estimated using the criterion of the frequency of aberrant cells. The arrangement of the flight biological container Biobloc made it possible to trace the location of tracks of individual HZE particles with Z>=6 and LET 200 keV/um. In seeds hit by HZE particles, for all exposure times, a statistically significant much higher yield of aberrant cells and also of cells containing multiple chromosome aberrations was observed than in the control material. The frequency of aberrant cells is markedly higher (by a factor of 1,5) in seeds hit than in non-hit ones. The changes of the yield of aberrant cells as a function of the absorbed dose (3.2-63.4 mGy) and the fluence (4.8-44.2 particles/cm2) are linear for the exposure duration ranging from 40 to 457 days.

  7. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice

    PubMed Central

    Deshpande, Krutika T.; Liu, Shinlan; McCracken, Jennifer M.; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N.; Richard, Zachary C.; O’Neil, Maura F.; Pritchard, Michele T.

    2016-01-01

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure. PMID:26751492

  8. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

    PubMed

    Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

    2015-12-02

    Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

  9. Brain glycogen decreases during prolonged exercise

    PubMed Central

    Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2011-01-01

    Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

  10. Exposure-lag-response in Longitudinal Studies: Application of Distributed Lag Non-linear Models in an Occupational Cohort.

    PubMed

    Neophytou, Andreas M; Picciotto, Sally; Brown, Daniel M; Gallagher, Lisa E; Checkoway, Harvey; Eisen, Ellen A; Costello, Sadie

    2018-02-13

    Prolonged exposures can have complex relationships with health outcomes, as timing, duration, and intensity of exposure are all potentially relevant. Summary measures such as cumulative exposure or average intensity of exposure may not fully capture these relationships. We applied penalized and unpenalized distributed lag non-linear models (DLNMs) with flexible exposure-response and lag-response functions in order to examine the association between crystalline silica exposure and mortality from lung cancer and non-malignant respiratory disease in a cohort study of 2,342 California diatomaceous earth workers, followed 1942-2011. We also assessed associations using simple measures of cumulative exposure assuming linear exposure-response and constant lag-response. Measures of association from DLNMs were generally higher than from simpler models. Rate ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3 during lag years 31-50 prior to the age of observed cases were 1.47 (95% confidence interval (CI) 0.92, 2.35) for lung cancer and 1.80 (95% CI: 1.14, 2.85) for non-malignant respiratory disease. Rate ratios from the simpler models for the same exposure scenario were 1.15 (95% CI: 0.89-1.48) and 1.23 (95% CI: 1.03-1.46) respectively. Longitudinal cohort studies of prolonged exposures and chronic health outcomes should explore methods allowing for flexibility and non-linearities in the exposure-lag-response. © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  11. A comparative study of QT prolongation with serotonin reuptake inhibitors.

    PubMed

    Ojero-Senard, Ana; Benevent, Justine; Bondon-Guitton, Emmanuelle; Durrieu, Geneviève; Chebane, Leila; Araujo, Melanie; Montastruc, Francois; Montastruc, Jean-Louis

    2017-10-01

    QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the "suspected" SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD. In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90-3.87]) or escitalopram (2.50 [2.11-2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients. This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.

  12. Comparative Benchmark Dose Modeling as a Tool to Make the First Estimate of Safe Human Exposure Levels to Lunar Dust

    NASA Technical Reports Server (NTRS)

    James, John T.; Lam, Chiu-wing; Scully, Robert R.

    2013-01-01

    Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.

  13. Evaluation of the CNS and cardiovascular effects of prolonged exposure to bromotrifluromethane (CBrF3)

    NASA Technical Reports Server (NTRS)

    Geller, I.; Garcia, C.; Gleiser, C.; Haines, R., Jr.; Hamilton, M.; Hartmann, R., Jr.; Mendez, V.; Samuels, A.; Miguel, M. S.

    1981-01-01

    The proposed use of bromotrifluoromethane (CBrF3) as a fire extinguishant in aircraft, spacecraft and submarines has stimulated increasing interest and research in the toxicological properties of this compound. In a spacecraft, because of its unique recirculating life support system, the introduction of CBrF3 by leakage or intentional discharge, will result in continuous exposure of crewman to low concentrations of this compound for periods of up to 7 days, or possibly even longer. The effects of low concentrations of CBrF3, under continuous exposure conditions, on the CNS and cardiovascular systems of animals to enable an assessment of these risks were investigated.

  14. Development of a reservoir type prolonged release system with felodipine via simplex methodology

    PubMed Central

    IOVANOV, RAREŞ IULIU; TOMUŢĂ, IOAN; LEUCUŢA, SORIN EMILIAN

    2016-01-01

    Background and aims Felodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method. Methods The first step of the Simplex method was to study the influence of the granules coating method on the felodipine release. Furthermore the influence of the coating polymer type, the percent of the coating polymer and the percent of pore forming agent in the coating on the felodipine release were studied. Afterwards these two steps of the experimental design the percent of Surelease applied on the felodipine loaded granules and the percent of pore former in the polymeric coating formulation variables were studied. The in vitro dissolution of model drug was performed in phosphate buffer solution (pH 6.5) with 1% sodium lauryl sulfate. The released drug quantification was done using an HPLC method. The release kinetics of felodipine from the final granules was assessed using different mathematical models. Results A 12 hours release was achieved using granules with the size between 315–500 μm coated with 45% Surelease with different pore former ratios in the coating via the top-spray method. Conclusion We have prepared prolonged release coated granules with felodipine using a fluid bed system based on the Simplex method. The API from the studied final formulations was released over a 12 hours period and the release kinetics of the model drug substance from the optimized preparations fitted best the Higuchi and Peppas kinetic models. PMID:27004036

  15. Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study

    PubMed Central

    Kertai, Miklos D.; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P.; Daubert, James P.; Podgoreanu, Mihai V.

    2016-01-01

    Background We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. Methods All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as >440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes – involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes–was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. Results After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). Conclusion The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery. PMID:26858093

  16. Nanoconjugation prolongs endosomal signaling of the epidermal growth factor receptor and enhances apoptosis

    NASA Astrophysics Data System (ADS)

    Wu, L.; Xu, F.; Reinhard, B. M.

    2016-07-01

    mediated apoptosis at effective concentrations that do not induce apoptosis in the case of free EGF. Overall, these findings indicate nanoconjugation as a rational strategy for modifying signaling that acts by modulating the temporo-spatial distribution of the activated EGF-EGFR ligand-receptor complex. Electronic supplementary information (ESI) available: DLS data of NP-EGF in growth medium; MTT cell viability assay; validation of MW-NP uptake; positive controls for pharmacological inhibitors; EEA1 background for NP-EGF incubated with cell lysate; phosphorylation for EGF-Alexa647; live cell dynamic colocalization movie of MDA-MB-468 cells expressing Rab5a-GFP (green) 4.5 h after exposure to 8 pM NP-EGF (red). See DOI: 10.1039/c6nr02974d

  17. QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update.

    PubMed

    Beach, Scott R; Celano, Christopher M; Sugrue, Alan M; Adams, Caitlin; Ackerman, Michael J; Noseworthy, Peter A; Huffman, Jeff C

    Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications. We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients. In this nonsystematic review, we aimed to carefully and intensively identify new articles by utilizing a structured PubMed search from 2012-present. QT prolongation remains an imperfect, though well-established marker of risk for TdP. Among antidepressant medications, citalopram does appear to prolong the QT interval more than other selective serotonin reuptake inhibitors, though the clinical significance of this prolongation remains unclear. Escitalopram appears to prolong the QT interval to a lesser extent. Haloperidol carries a risk for QT prolongation, but the assertion that intravenous haloperidol is inherently riskier may be confounded by its primary use in medically ill populations. Among atypical antipsychotic agents, ziprasidone-and possibly iloperidone-is associated with the greatest QT prolongation, whereas aripiprazole appears safest from this standpoint. The evidence for clinically meaningful QT prolongation with most classes of psychiatric agents remains minimal. The most important risk-reducing intervention clinicians can make is undertaking a careful analysis of other QT risk factors when prescribing psychiatric medications. Copyright © 2017 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Supplementation of Ascorbic Acid in Weanling Horses Following Prolonged Transportation

    PubMed Central

    Ralston, Sarah; Stives, Michelle

    2012-01-01

    Simple Summary Horses normally synthesize adequate amounts of ascorbic acid (vitamin C) in their liver to meet their needs for the vitamin. However, prolonged stress results in low plasma concentrations and reduced immune function. Weanling horses were supplemented with ascorbic acid for 5 or 10 days or no ascorbic acid (4 per group) following 50+ hours of transportation. Supplementation caused increases in plasma concentrations but both supplemented groups had decreased plasma ascorbic acid for 1 to 3 weeks following cessation of supplementation, possibly due to suppressed synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided. Abstract Though horses synthesize ascorbic acid in their liver in amounts that meet their needs under normal circumstances, prolonged stress results in low plasma concentrations due to enhanced utilization and renal excretion and can reduce immune function. It was hypothesized that plasma ascorbic acid could be maintained in weanling horses by oral supplementation following prolonged transportation. Weanlings were supplemented with no ascorbic acid (Tx 0: n = 4), 5 grams ascorbic acid twice daily for 5 days (Tx 1: n = 4) or for 10 days (Tx 2: n = 4) following >50 hours of transportation. Supplementation caused slight (P < 0.2) increases in plasma ascorbic acid concentrations. Both supplemented groups had decreased (P < 0.05) plasma concentrations for 1 to 3 weeks following cessation of supplementation, possibly due to increased renal excretion or suppressed hepatic synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided. PMID:26486916

  19. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain.

    PubMed

    Gerlofs-Nijland, Miriam E; van Berlo, Damien; Cassee, Flemming R; Schins, Roel P F; Wang, Kate; Campbell, Arezoo

    2010-05-17

    The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-kappaB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-alpha and TNF Receptor-subtype I (TNF-RI). Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to

  20. How Long Will I Be Blue? Prolonged Skin Staining Following Sentinel Lymph Node Biopsy Using Intradermal Patent Blue Dye

    PubMed Central

    Gumus, Metehan; Gumus, Hatice; Jones, Sue E; Jones, Peter A; Sever, Ali R; Weeks, Jennifer

    2013-01-01

    Summary Background Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. Patients and Methods 236 consecutive patients who had undergone breast conserving surgery and SLNB for breast cancer were reviewed prospectively from January 2007 to December 2009. Results Of the 236 patients, 2 had undergone bilateral surgery, and 41 had been examined in consecutive yearly reviews. Blue discoloration remained visible at the injection site after 12, 24, and > 36 months in 36.5, 23.6, and 8.6% of the patients, respectively. Conclusion The use of patent blue for identification of the sentinel lymph node in patients undergoing breast cancer surgery may result in prolonged discoloration of the skin at the injection site. PMID:24415970

  1. Recovery from welding-fume-exposure-induced MRI T1 signal intensities after cessation of welding-fume exposure in brains of cynomolgus monkeys.

    PubMed

    Han, Jeong Hee; Chung, Yong Hyun; Park, Jung Duck; Kim, Choong Yong; Yang, Seoung Oh; Khang, Hyun Soo; Cheong, Hae Kwan; Lee, Jong Seong; Ha, Chang Soo; Song, Chang-Woo; Kwon, Il Hoon; Sung, Jae Hyuck; Heo, Jeong Doo; Kim, Na-Young; Huang, Mingai; Cho, Myung Haing; Yu, Il Je

    2008-09-01

    The shortening of the MRI T1 relaxation time, indicative of a high signal intensity in a T1-weighted MRI, is known as a useful biomarker for Mn exposure after short-term welding-fume exposure. A previous monkey experimental study found that the T1 relaxation times decreased time-dependently after exposure, and a visually detectable high signal intensity appeared after 150 days of exposure. The nadir for the shortening of the T1 relaxation time was also previously found to correspond well with the blood Mn concentration in welders, suggesting a correlation between a prolonged high blood Mn concentration and shortened T1 relaxation time. Accordingly, to clarify the clearance of the brain Mn concentration after the cessation of welding-fume exposure, cynomolgus monkeys were assigned to 3 groups-unexposed, low dose (31 mg/m(3) total suspended particulate (TSP), 0.9 mg Mn/m(3)), and high dose (62 mg/m(3) TSP, 1.95 mg Mn/m(3))-and exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day for 8 mo in an inhalation chamber system equipped with an automatic fume generator. After reaching the peak MRI T1 signal intensity (shortest T1 relaxation time), the monkeys were allowed to recover by ceasing the welding-fume exposure. Within 2 mo, the MRI T1 signal intensities for the exposed monkeys returned to nearly the same level as those for the unexposed monkeys, indicating the potential for recovery from a high MRI T1 signal intensity induced by welding-fume exposure, even after prolonged exposure. Clearance of the Mn tissue concentration was also demonstrated in the globus pallidus, plus other tissues from the brain, liver, spleen, and blood. In contrast, there was no clearance of the lung concentrations of Mn, indicating that a soluble form of Mn was transported to the blood and brain. Therefore, the solubility of Mn in welding fumes would appear to be an important determinant as regards the retention of blood Mn levels and brain tissue Mn

  2. New technique to prevent prolonged air leak: use of 'Tachosuture' technique.

    PubMed

    Nishida, Tatsuya; Mikami, Iwao; Fujii, Yoshitaka

    2017-02-01

    Prolonged air leak (defined as air leak >7 days), caused by pulmonary resection or alveolar-pleural fistula, increases postoperative morbidity, prolongs hospital stay and increases healthcare costs. We describe a new technique ('Tachosuture' technique) to prevent prolonged air leak. The key point of this new technique is that air leak is classified into three types and an absorbable suture is added to a TachoSil ® patch in each type to prevent detachment from the lung parenchyma. Between August 2013 and March 2016, 40 patients underwent thoracoscopic surgery using 'Tachosuture' technique. Postoperative air leak always stopped within 3 days (95% confidence interval for the absence of prolonged air leak: 92.5-100%). It is considered that this simple technique is useful to prevent prolonged air leak.

  3. Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood

    PubMed Central

    Huang, Lianyan; Yang, Guang

    2014-01-01

    Background Recent studies in rodents suggest that repeated and prolonged anesthetic exposure at early stages of development leads to cognitive and behavioral impairments later in life. However, the underlying mechanism remains unknown. In this study, we tested whether exposure to general anesthesia during early development will disrupt the maturation of synaptic circuits and compromise learning-related synaptic plasticity later in life. Methods Mice received ketamine/xylazine (20/3 mg/kg) anesthesia for one or three times, starting at either early [postnatal day 14 (P14)] or late (P21) stages of development (n=105). Control mice received saline injections (n=34). At P30, mice were subjected to rotarod motor training and fear conditioning. Motor learning-induced synaptic remodeling was examined in vivo by repeatedly imaging fluorescently-labeled postsynaptic dendritic spines in the primary motor cortex before and after training using two-photon microscopy. Results Three exposures to ketamine/xylazine anesthesia between P14–18 impair the animals’ motor learning and learning-dependent dendritic spine plasticity [new spine formation, 8.4 ± 1.3% (mean ± SD) versus 13.4 ± 1.8%, P = 0.002] without affecting fear memory and cell apoptosis. One exposure at P14 or three exposures between P21–25 has no effects on the animals’ motor learning or spine plasticity. Finally, enriched motor experience ameliorates anesthesia-induced motor learning impairment and synaptic deficits. Conclusion Our study demonstrates that repeated exposures to ketamine/xylazine during early development impair motor learning and learning-dependent dendritic spine plasticity later in life. The reduction in synaptic structural plasticity may underlie anesthesia-induced behavioral impairment. PMID:25575163

  4. Multiple exposures to swine barn air induce lung inflammation and airway hyper-responsiveness

    PubMed Central

    Charavaryamath, Chandrashekhar; Janardhan, Kyathanahalli S; Townsend, Hugh G; Willson, Philip; Singh, Baljit

    2005-01-01

    Background Swine farmers repeatedly exposed to the barn air suffer from respiratory diseases. However the mechanisms of lung dysfunction following repeated exposures to the barn air are still largely unknown. Therefore, we tested a hypothesis in a rat model that multiple interrupted exposures to the barn air will cause chronic lung inflammation and decline in lung function. Methods Rats were exposed either to swine barn (8 hours/day for either one or five or 20 days) or ambient air. After the exposure periods, airway hyper-responsiveness (AHR) to methacholine (Mch) was measured and rats were euthanized to collect bronchoalveolar lavage fluid (BALF), blood and lung tissues. Barn air was sampled to determine endotoxin levels and microbial load. Results The air in the barn used in this study had a very high concentration of endotoxin (15361.75 ± 7712.16 EU/m3). Rats exposed to barn air for one and five days showed increase in AHR compared to the 20-day exposed and controls. Lungs from the exposed groups were inflamed as indicated by recruitment of neutrophils in all three exposed groups and eosinophils and an increase in numbers of airway epithelial goblet cells in 5- and 20-day exposure groups. Rats exposed to the barn air for one day or 20 days had more total leukocytes in the BALF and 20-day exposed rats had more airway epithelial goblet cells compared to the controls and those subjected to 1 and 5 exposures (P < 0.05). Bronchus-associated lymphoid tissue (BALT) in the lungs of rats exposed for 20 days contained germinal centers and mitotic cells suggesting activation. There were no differences in the airway smooth muscle cell volume or septal macrophage recruitment among the groups. Conclusion We conclude that multiple exposures to endotoxin-containing swine barn air induce AHR, increase in mucus-containing airway epithelial cells and lung inflammation. The data also show that prolonged multiple exposures may also induce adaptation in AHR response in the exposed

  5. Prolonged sexual abstinence after childbirth: gendered norms and perceived family health risks. Focus group discussions in a Tanzanian suburb

    PubMed Central

    2013-01-01

    Background Prolonged sexual abstinence after childbirth is a socio-cultural practice with health implications, and is described in several African countries, including Tanzania. This study explored discourses on prolonged postpartum sexual abstinence in relation to family health after childbirth in low-income suburbs of Dar es Salaam, Tanzania. Methods Data for the discourse analysis were collected through focus group discussions with first-time mothers and fathers and their support people in Ilala, Dar es Salaam, Tanzania. Results In this setting, prolonged sexual abstinence intended at promoting child health was the dominant discourse in the period after childbirth. Sexual relations after childbirth involved the control of sexuality for ensuring family health and avoiding the social implications of non-adherence to sexual abstinence norms. Both abstinence and control were emphasised more with regard to women than to men. Although the traditional discourse on prolonged sexual abstinence for protecting child health was reproduced in Ilala, some modern aspects such as the use of condoms and other contraceptives prevailed in the discussion. Conclusion Discourses on sexuality after childbirth are instrumental in reproducing gender-power inequalities, with women being subjected to more restrictions and control than men are. Thus, interventions that create openness in discussing sexual relations and health-related matters after childbirth and mitigate gendered norms suppressing women and perpetuating harmful behaviours are needed. The involvement of males in the interventions would benefit men, women, and children through improving the gender relations that promote family health. PMID:23316932

  6. Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials

    PubMed Central

    2011-01-01

    Background The emergence of multi-drug resistant Gram-negatives (MDRGNs) coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion. Methods Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models. Results Fourteen randomized controlled trials (RCTs) were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37) or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06) compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws. Conclusions No clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed. PMID:21696619

  7. Exposure and non-fear emotions: A randomized controlled study of exposure-based and rescripting-based imagery in PTSD treatment.

    PubMed

    Langkaas, Tomas Formo; Hoffart, Asle; Øktedalen, Tuva; Ulvenes, Pål G; Hembree, Elizabeth A; Smucker, Mervin

    2017-10-01

    Interventions involving rescripting-based imagery have been proposed as a better approach than exposure-based imagery when posttraumatic stress disorder (PTSD) is associated with emotions other than fear. Prior research led to the study's hypotheses that (a) higher pretreatment non-fear emotions would predict relatively better response to rescripting as compared to exposure, (b) rescripting would be associated with greater reduction in non-fear emotions, and (c) pretreatment non-fear emotions would predict poor response to exposure. A clinically representative sample of 65 patients presenting a wide range of traumas was recruited from patients seeking and being offered PTSD treatment in an inpatient setting. Subjects were randomly assigned to 10 weeks of treatment involving either rescripting-based imagery (Imagery Rescripting; IR) or exposure-based imagery (Prolonged Exposure; PE). Patients were assessed on outcome and emotion measures at pretreatment, posttreatment and 12 months follow-up. Comparison to control benchmarks indicated that both treatments were effective, but no outcome differences between them appeared. None of the initial hypotheses were supported. The results from this study challenge previous observations and hypotheses about exposure mainly being effective for fear-based PTSD and strengthen the notion that exposure-based treatment is a generally effective treatment for all types of PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Exposure Measurement Error in PM2.5 Health Effects Studies: A Pooled Analysis of Eight Personal Exposure Validation Studies

    EPA Science Inventory

    Background: Exposure measurement error is a concern in long-term PM2.5 health studies using ambient concentrations as exposures. We assessed error magnitude by estimating calibration coefficients as the association between personal PM2.5 exposures from validation studies and typ...

  9. Validation of Open-Heart Intraoperative Risk score to predict a prolonged intensive care unit stay for adult patients undergoing cardiac surgery with cardiopulmonary bypass

    PubMed Central

    Tribuddharat, Sirirat; Sathitkarnmanee, Thepakorn; Ngamsaengsirisup, Kriangsak; Wongbuddha, Chawalit

    2018-01-01

    Background A prolonged stay in an intensive care unit (ICU) after cardiac surgery with cardiopulmonary bypass (CPB) increases the cost of care as well as morbidity and mortality. Several predictive models aim at identifying patients at risk of prolonged ICU stay after cardiac surgery with CPB, but almost all of them involve a preoperative assessment for proper resource management, while one – the Open-Heart Intraoperative Risk (OHIR) score – focuses on intra-operative manipulatable risk factors for improving anesthetic care and patient outcome. Objective We aimed to revalidate the OHIR score in a different context. Materials and methods The ability of the OHIR score to predict a prolonged ICU stay was assessed in 123 adults undergoing cardiac surgery (both coronary bypass graft and valvular surgery) with CPB at two tertiary university hospitals between January 2013 and December 2014. The criteria for a prolonged ICU stay matched a previous study (ie, a stay longer than the median). Results The area under the receiver operating characteristic curve of the OHIR score to predict a prolonged ICU stay was 0.95 (95% confidence interval 0.90–1.00). The respective sensitivity, specificity, positive predictive value, and accuracy of an OHIR score of ≥3 to discriminate a prolonged ICU stay was 93.10%, 98.46%, 98.18%, and 95.9%. Conclusion The OHIR score is highly predictive of a prolonged ICU stay among intraopera-tive patients undergoing cardiac surgery with CPB. The OHIR comprises of six risk factors, five of which are manipulatable intraoperatively. The OHIR can be used to identify patients at risk as well as to improve the outcome of those patients. PMID:29379295

  10. Prolonged ketamine exposure induces increased activity of the GluN2B-containing N-methyl-d-aspartate receptor in the anterior cingulate cortex of neonatal rats.

    PubMed

    Kokane, Saurabh S; Gong, Kerui; Jin, Jianhui; Lin, Qing

    2017-09-01

    Ketamine is a commonly used anesthetic among pediatric patients due to its high efficacy. However, it has been demonstrated by several preclinical studies that, widespread accelerated programmed death of neurons (neuroapoptosis) occurs due to prolonged or repeated exposure to ketamine specifically in the neonatal brain. Therefore, an emphasis on understanding the molecular mechanisms underlying this selective vulnerability of the neonatal brain to ketamine-induced neuroapoptosis becomes important in order to identify potential therapeutic targets, which would help prevent or at least ameliorate this neuroapoptosis. In this study, we demonstrated that repeated ketamine administration (6 injections of 20mg/kg dose given over 12h time period) in neonatal (postnatal day 7; PND 7) Sprague-Dawley rats induced a progressive increase in N-methyl-d-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) in the neurons of the anterior cingulate cortex (ACC) for up to 6h after the last ketamine dose. Specifically, we observed that the increased EPSCs were largely mediated by GluN2B-containing NMDARs in the neurons of the ACC. Along with increased synaptic transmission, there was also a significant increase in the expression of the GluN2B-containing NMDARs as well. Taken together, these results showed that after repeated exposure to ketamine, the synaptic transmission mediated by GluN2B-containing NMDARs was significantly increased in the neonatal brain. This was significant as it showed for the first time that ketamine had subunit-specific effects on GluN2B-containing NMDARs, potentially implicating the involvement of these subunits in the increased vulnerability of immature neurons of the neonatal brain to ketamine-induced neuroapoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Estimating pediatric general anesthesia exposure: Quantifying duration and risk.

    PubMed

    Bartels, Devan Darby; McCann, Mary Ellen; Davidson, Andrew J; Polaner, David M; Whitlock, Elizabeth L; Bateman, Brian T

    2018-05-02

    Understanding the duration of pediatric general anesthesia exposure in contemporary practice is important for identifying groups at risk for long general anesthesia exposures and designing trials examining associations between general anesthesia exposure and neurodevelopmental outcomes. We performed a retrospective cohort analysis to estimate pediatric general anesthesia exposure duration during 2010-2015 using the National Anesthesia Clinical Outcomes Registry. A total of 1 548 021 pediatric general anesthetics were included. Median general anesthesia duration was 57 minutes (IQR: 28-86) with 90th percentile 145 minutes. Children aged <1 year had the longest median exposure duration (79 minutes, IQR: 39-119) with 90th percentile 210 minutes, and 13.7% of this very young cohort was exposed for >3 hours. High ASA physical status and care at a university hospital were associated with longer exposure times. While the vast majority (94%) of children undergoing general anesthesia are exposed for <3 hours, certain groups may be at increased risk for longer exposures. These findings may help guide the design of future trials aimed at understanding neurodevelopmental impact of prolonged exposure in these high-risk groups. © 2018 John Wiley & Sons Ltd.

  12. Nickel on the market: a baseline survey of articles in 'prolonged contact' with skin.

    PubMed

    Ringborg, Evelina; Lidén, Carola; Julander, Anneli

    2016-08-01

    In April 2014, the European Chemicals Agency defined the concept of 'prolonged contact with skin' as used in the EU nickel restriction. To establish a baseline of nickel-releasing items on the Swedish market conforming with the EU nickel restriction according to the definition of 'prolonged contact' with the skin. We performed a limited market survey in Stockholm, Sweden. Items with metallic parts that come into contact with the skin, except those explicitly mentioned in the legal text, were chosen. The dimethylglyoxime (DMG) test was used to evaluate nickel release. One hundred and forty-one items belonging to one of three categories - accessories, utensils for needlework, painting and writing (called utensils), and electronic devices - were tested in the study. Forty-four percent of all items were DMG test-positive (releasing nickel), and 9% gave a doubtful DMG test result. The large proportion of nickel-releasing items in the present study shows clearly that broader parts of industry need to take action to prevent nickel allergy. The high proportion of DMG test-positive items indicates that there is still much work to be done to reduce the nickel exposure of the population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

    NASA Technical Reports Server (NTRS)

    Baevsky, R. M.; Bennett, B. S.; Bungo, M. W.; Charles, J. B.; Goldberger, A. L.; Nikulina, G. A.

    1997-01-01

    This article presents selected findings obtained with Holter monitoring from two crew members of the expedition, performed during a 175-day space mission on board orbital space station "MIR." Using mathematical processing of daily cardiointervals files, 5-minute sections of records were analyzed consecutively. Then, the average daily values of indices, the average-per-every-eight-hours values (morning, evening, night) and mean values per hour were computed. The results of analysis showed that prolonged exposure of man to microgravity conditions leads to important functional alteration in human neuroautonomic regulatory mechanisms. Both crew members had significant increase of heart rate, the rise of stress index, the decrease in power of the spectrum in the range of respiratory sinus arrhythmia. These marked signs of activation of the sympathetic section of the vegetative nervous system showed individual variations. The analysis of the daily collection of cardiointervals with Holter monitoring allows us to understand and forecast the functional feasibilities of the human organism under a variety of stress conditions associated with acute and chronic microgravity exposure.

  14. Wash and Wean: Bathing Patients Undergoing Weaning Trials During Prolonged Mechanical Ventilation

    PubMed Central

    Happ, Mary Beth; Tate, Judith A.; Swigart, Valerie A.; DiVirgilio-Thomas, Dana; Hoffman, Leslie A.

    2010-01-01

    BACKGROUND Bathing is a fundamental nursing care activity performed for or with the self-assistance of critically ill patients. Few studies address caregiver and/or patient-family perspectives about bathing activity during weaning from prolonged mechanical ventilation. OBJECTIVE To describe practices and beliefs about bathing patients during weaning from prolonged mechanical ventilation (PMV). METHODS Secondary analysis of qualitative data (observational field notes, interviews, and clinical record review) from a larger ethnographic study involving 30 patients weaning from PMV and the clinicians who cared for them using basic qualitative description. RESULTS Bathing, hygiene, and personal care were highly valued and equated with “good” nursing care by families and nurses. Nurses and respiratory therapists reported “working around” bath time and promoted conducting weaning trials before or after bathing. Patients were nevertheless bathed during weaning trials despite clinicians expressed concerns for energy conservation. Clinicians’ recognized individual patient response to bathing during PMV weaning trials. CONCLUSION Bathing is a central care activity for PMV patients and a component of daily work processes in the ICU. Bathing requires assessment of patient condition and activity tolerance and nurse-respiratory therapist negotiation and accommodation with respect to the initiation and/or continuation of PMV weaning trials during bathing. Further study is needed to validate the impact (or lack of impact) of various timing strategies for bathing PMV patients. PMID:20561877

  15. Radiation burdens for humans on prolonged exomagnetospheric voyages.

    PubMed

    Moore, F D

    1992-03-01

    The severity of radiation exposure for astronauts outside the magnetosphere poses a critical unanswered question bearing on the use of manned vehicles in extended exploration of the solar system (moon, Mars). Such prolonged exomagnetospheric voyages (1-3 years) enter a radiologic environment more severe than that of low earth orbit, an annual dose equivalent in the range of 0.3-0.5 Sv (30-50 rem), and a lifetime excess cancer fatality risk of 3-5% due to low linear-energy-transfer components of galactic cosmic radiation alone. To this calculus must be added estimates for high-atomic-number, high-energy particles, the probability of solar particle events, and the limited effectiveness of shielding. For a 3-year Mars voyage these could elevate the dose equivalent to 1.5-2.25 Sv (150-225 rem) total (0.5-0.75 Sv [50-75 rem] annual) and risks to 5-9% excess cancer fatality. Both the mission (civilian scientific research) and the alternatives (unmanned robotic devices) enter the policy decision here. This paper presents a brief review of pertinent physical and biological data and of research urgently needed before reaching a decision on this question.

  16. Prolonged restricted sitting effects in UH-60 helicopters.

    PubMed

    Games, Kenneth E; Lakin, Joni M; Quindry, John C; Weimar, Wendi H; Sefton, JoEllen M

    2015-01-01

    Advances in flight technologies and the demand for long-range flight have increased mission lengths for U.S. Army Black Hawk UH-60 crewmembers. Prolonged mission times have increased reports of pilot discomfort and symptoms of paresthesia thought to be due to UH-60 seat design and areas of locally high pressure. Discomfort created by the seat-system decreases situational awareness, putting aviators and support crew at risk of injury. Therefore, the purpose of this study was to examine the effects of prolonged restricted sitting in a UH-60 on discomfort, sensory function, and vascular measures in the lower extremities. There were 15 healthy men (age = 23.4 ± 3.1 yr) meeting physical flight status requirements who sat in an unpadded, UH-60 pilot's seat for 4 h while completing a common cognitive task. During the session, subjective discomfort, sensory function, and vascular function were measured. Across 4 h of restricted sitting, subjective discomfort increased using the Category Partitioning Scale (30.27 point increase) and McGill Pain Questionnaire (8.53 point increase); lower extremity sensory function was diminished along the S1 dermatome; and skin temperature decreased on both the lateral (2.85°C decrease) and anterior (2.78°C decrease) aspects of the ankle. The results suggest that prolonged sitting in a UH-60 seat increases discomfort, potentially through a peripheral nervous or vascular system mechanism. Further research is needed to understand the etiology and onset of pain and paresthesia during prolonged sitting in UH-60 pilot seats. Games KE, Lakin JM, Quindry JC, Weimar WH, Sefton JM. Prolonged restricted sitting effects in UH-60 helicopters.

  17. Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

    PubMed

    Ogundele, Olalekan M; Ebenezer, Philip J; Lee, Charles C; Francis, Joseph

    2017-06-14

    Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (p<0.001), hippocampal (p<0.001) and cortical (p<0.05) IGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; p<0.001), and changes in neurotransmitters (VGLUT2, Tyrosine hydroxylase, GABA, ChAT). Furthermore, naïve stressed rats recorded a significant decrease in post-synaptic marker (PSD-95; p<0.01) and synaptic regulator (CaMKIIα; p<0.001). As part of the synaptic response to a decrease in brain CaMKIIα, small ion conductance channel (KCa2.2) was upregulated in the brain of naïve stressed rats (p<0.01). After a PET, an increase in IGF-1 (p<0.05) and IGF-1R was recorded in the Stress-PET group (p<0.001). As such, hippocampal (p<0.001), but not cortical (ns) synaptophysin expression increased in Stress-PET. Although PSD-95

  18. Mitochondrial Genetic Background Modifies the Relationship between Traffic-Related Air Pollution Exposure and Systemic Biomarkers of Inflammation

    PubMed Central

    Wittkopp, Sharine; Staimer, Norbert; Tjoa, Thomas; Gillen, Daniel; Daher, Nancy; Shafer, Martin; Schauer, James J.; Sioutas, Constantinos; Delfino, Ralph J.

    2013-01-01

    Background Mitochondria are the main source of reactive oxygen species (ROS). Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD). We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin. Objective We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production) in this panel (38 subjects and 417 observations). Methods Inflammation biomarkers were measured weekly in each subject (≤12 weeks), including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx), carbon monoxide (CO), organic carbon, elemental and black carbon (EC, BC); and particulate matter mass, three size fractions (<0.25 µm, 0.25–2.5 µm, and 2.5–10 µm in aerodynamic diameter). Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH), and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models. Results IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH), and with mass and oxidative potential of quasi-ultrafine particles <0.25 µm. These associations were stronger for haplogroup H than haplogroup U. Conclusions Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects. PMID:23717615

  19. Soudan Low Background Counting Facility (SOLO)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Attisha, Michael; Viveiros, Luiz de; Gaitksell, Richard

    2005-09-08

    The Soudan Low Background Counting Facility (SOLO) has been in operation at the Soudan Mine, MN since March 2003. In the past two years, we have gamma-screened samples for the Majorana, CDMS and XENON experiments. With individual sample exposure times of up to two weeks we have measured sample contamination down to the 0.1 ppb level for 238U / 232Th, and down to the 0.25 ppm level for 40K.

  20. Prolonged anticholinergic delirium following antihistamine overdose.

    PubMed

    Scott, James; Pache, David; Keane, Greg; Buckle, Helen; O'Brien, Natalie

    2007-06-01

    A case of anticholinergic delirium in a female adolescent is described, exploring the pharmacokinetic reasons for the prolonged time course and reviewing the management provided. A 14 year old female hospitalised for depression ingested large quantities of promethazine and cyproheptadine. A severe anticholinergic delirium ensued which resolved after six days, much longer than the expected duration. The likely cause of the prolonged delirium was the interaction of promethazine and fluvoxamine through the inhibition of the CYP2D6 enzyme. The patient's young age, the severity of the poisoning and the use of drugs with anticholinergic properties to manage the delirium may also have contributed. The delirium may have been reversed had a cholinesterase inhibitor been provided soon after the overdose.

  1. The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue

    PubMed Central

    Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C.

    2016-01-01

    Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt

  2. The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

    PubMed

    Ng, Deborah Hl; Wong, Joshua Gx; Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C

    2016-01-01

    Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt

  3. [Factors related to the QT prolongation in chronic renal failure].

    PubMed

    Kurosu, M; Ando, Y; Akimoto, T; Ono, S; Kusano, E; Asano, Y

    1999-04-01

    QT prolongation, a risk factor for arrhythmia and cardiac death, is observed in uremic patients. Though hypocalcemia, autonomic nerve dysfunction and cardiac hypertrophy are assumed to cause the uremic QT prolongation, the exact mechanism remains unspecified. We therefore examined factors related to the QT interval in chronic renal failure (CRF). Corrected QT interval (QTc) was significantly prolonged in CRF just before the induction of dialysis therapy (group A) compared with nephrotic syndrome with the intact or mildly impaired renal function (group B). QTc was also prolonged in acute renal failure (group C). Cardio-thoracic ratio, serum albumin and Ca correlated with QTc in group A, but not in B or C. A single HD session in group A failed to shorten QTc, despite a significant increase in serum Ca++. Autonomic dysfunction did not appear to be a major determinant of QT prolongation, since QTc was not different between diabetics and non-diabetics in group A and in chronic HD patients (group D). In group D, QTc did not correlate with SV1 + RV5 on ECG or left ventricular wall thickness (LVWT) on echocardiography. In another group of chronic HD patients (group E), there was no significant correlation between QTc and the parameters of left ventricular mass, plasma brain natriuretic peptide (BNP). However, in the patients subjected to repeated echocardiography in group D, QTc and LVWT changed in parallel. In a retrospective analysis of QTc in group D, QTc was maximally prolonged at the time of starting HD therapy, and gradually improved in the following 1-5 years in both diabetics and non-diabetics. In contrast, chronic CAPD patients (group F) revealed no improvement of QTc. Thus, uremic QT prolongation cannot be explained simply by any of the previously assumed factors, but appears to be affected by multiple factors, which are partially correctable by chronic HD therapy.

  4. Prolonged morphine treatment alters δ opioid receptor post-internalization trafficking.

    PubMed

    Ong, E W; Xue, L; Olmstead, M C; Cahill, C M

    2015-01-01

    The δ opioid receptor (DOP receptor) undergoes internalization both constitutively and in response to agonists. Previous work has shown that DOP receptors traffic from intracellular compartments to neuronal cell membranes following prolonged morphine treatment. Here, we examined the effects of prolonged morphine treatment on the post-internalization trafficking of DOP receptors. Using primary cultures of dorsal root ganglia neurons, we measured the co-localization of endogenous DOP receptors with post-endocytic compartments following both prolonged and acute agonist treatments. A departure from the constitutive trafficking pathway was observed following acute DOP receptor agonist-induced internalization by deltorphin II. That is, the DOP receptor underwent distinct agonist-induced post-endocytic sorting. Following prolonged morphine treatment, constitutive DOP receptor trafficking was augmented. SNC80 following prolonged morphine treatment also caused non-constitutive DOP receptor agonist-induced post-endocytic sorting. The μ opioid receptor (MOP receptor) agonist DAMGO induced DOP receptor internalization and trafficking following prolonged morphine treatment. Finally, all of the alterations to DOP receptor trafficking induced by both DOP and MOP receptor agonists were inhibited or absent when those agonists were co-administered with a DOP receptor antagonist, SDM-25N. The results support the hypothesis that prolonged morphine treatment induces the formation of MOP-DOP receptor interactions and subsequent augmentation of the available cell surface DOP receptors, at least some of which are in the form of a MOP/DOP receptor species. The pharmacology and trafficking of this species appear to be unique compared to those of its individual constituents. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The Authors. British

  5. Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit

    PubMed Central

    Tran, Lee; Hanavan, Paul D.; Campbell, Latoya E.; De Filippis, Elena; Lake, Douglas F.; Coletta, Dawn K.; Roust, Lori R.; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

    2016-01-01

    Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = – 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish

  6. Prolonged Exposure of Primary Human Muscle Cells to Plasma Fatty Acids Associated with Obese Phenotype Induces Persistent Suppression of Muscle Mitochondrial ATP Synthase β Subunit.

    PubMed

    Tran, Lee; Hanavan, Paul D; Campbell, Latoya E; De Filippis, Elena; Lake, Douglas F; Coletta, Dawn K; Roust, Lori R; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

    2016-01-01

    Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = - 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish

  7. Cardiac Teratogenicity in Mouse Maternal Phenylketonuria: Defining phenotype parameters and genetic background influences

    PubMed Central

    Seagraves, Nikki J.; McBride, Kim L.

    2012-01-01

    Maternal phenylketonuria (MPKU) is a syndrome including cardiovascular malformations (CVMs), microcephaly, intellectual impairment, and small for gestational age, caused by in-utero exposure to elevated serum phenylalanine (Phe) due to PKU in the mother. It is becoming a public health concern as more women with PKU reach child bearing age. Although a mouse model of PKU, BTBR Pahenu2, has been available for 20 years, it has not been well utilized for studying MPKU. We used this model to delineate critical parameters in Phe cardiovascular teratogenicity and study the effect of genetic background. Dosing and timing experiments were performed with the BTBR Pahenu2 mouse. A dose response curve was noted, with CVM rates at maternal serum Phe levels <360 μM (control), 360 – 600 μM (low), 600 – 900 μM (mid), and >900μM (high) of 11.86%, 16.67%, 30.86%, and 46.67% respectively. A variety of CVMs were noted on the BTBR background, including double outlet right ventricle (DORV), aortic arch artery (AAA)abnormalities, and ventricular septal defects (VSDs). Timed exposure experiments identified a teratogenic window from embryonic day 8.5-13.5, with higher rates of conotruncal and valve defects occurring in early exposure time and persistent truncus arteriosus (PTA) and aortic arch branching abnormalities occurring with late exposure. Compared to the BTBR strain, N10+ Pahenu2 congenics on the C3H/HeJ background had higher rates of CVMs in general and propensity to left ventricular outflow tract (LVOT) malformations, while the C57B/L6 background had similar CVM rates but predominately AAA abnormalities. We have delineated key parameters of Phe cardiovascular teratogenicity, demonstrated the utility of this MPKU model on different mouse strains, and shown how genetic background profoundly affects the phenotype. PMID:22951387

  8. Prolonged social withdrawal disorder: a hikikomori case in Spain.

    PubMed

    Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

    2014-09-01

    The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

  9. The significance of nanomaterial post-exposure responses in Daphnia magna standard acute immobilisation assay: Example with testing TiO2 nanoparticles.

    PubMed

    Novak, Sara; Jemec Kokalj, Anita; Hočevar, Matej; Godec, Matjaž; Drobne, Damjana

    2018-05-15

    One of the most widely used aquatic standarized tests for the toxicity screening of chemicals is the acute toxicity test with the freshwater crustacean Daphnia magna, which has also been applied in the toxicity screening of manufactured nanoparticles (NPs). However, in the case of non-soluble NPs most of the results of this test have showed no effect. The aim of the work presented here was to modify the standardized test by the least possible extent to make it more sensitive for non-soluble particles. The standard acute immobilisation assay with daphnids was modified by prolonging the exposure period and by measuring additional endpoints. Daphnids were exposed to TiO 2 NPs in a standard acute test (48h of exposure), a standard acute test (48h of exposure) followed by 24h recovery period in clean medium or a prolonged exposure in the NPs solutions totaling 72h. Together with immobility, the adsorption of NPs to body surfaces was also observed as an alternative measure of the NPs effects. Our results showed almost no effect of TiO 2 NPs on D. magna after the 48h standard acute test, while immobility was increased when the exposure period to TiO 2 NPs was prolonged from 48h to 72h. Even when daphnids were transferred to clean medium for additional 24h after 48h of exposure to TiO 2 NPs the immobility increased. We conclude that by transferring the daphnids to clean medium at the end of the 48h exposure to TiO 2 NPs, the delayed effects of the tested material can be seen. This methodological step could improve the sensitivity of D. magna test as a model in nanomaterial environmental risk assessment. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Occupational heat exposure among municipal workers.

    PubMed

    Uejio, Christopher K; Morano, Laurel Harduar; Jung, Jihoon; Kintziger, Kristina; Jagger, Meredith; Chalmers, Juanita; Holmes, Tisha

    2018-06-05

    Outdoor workers face elevated and prolonged heat exposures and have limited access to air-conditioned spaces. This study's overarching research aim is to increase knowledge of municipal worker heat exposure and adaptation practices. The study's sub-objectives are: (1) quantifying exposure misclassification from estimating personal heat exposure from the official weather station; (2) surveying worker's knowledge and practices to adapt to extreme heat; and (3) relating heat exposure and adaptation practices to self-reported thermal comfort. Participants wore a personal heat exposure sensor over 7 days from June 1st to July 3rd, 2015 in Tallahassee, Florida US. Next, participants confirmed the days that they wore the sensor and reported their daily thermal comfort and heat adaptations. Finally, participants completed an extreme heat knowledge, attitudes, and practices survey. Some participants (37%) experienced hotter and more humid conditions (heat index > 2) than the weather station. The most common heat adaptations were staying hydrated (85%), wearing a hat (46%), and seeking shade (40%). During work hours, higher temperatures increased the odds (odds ratio: 1.21, 95% confidence interval: 1.03-1.41, p = 0.016) of a participant feeling too hot. Shifting work duty indoors made workers to feel more comfortable (odds ratio: 0.28, 95% confidence interval: 0.11-0.70, p = 0.005). In hot and humid climates, everyday, heat exposures continuously challenge the health of outdoor workers.

  11. Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With Posttraumatic Stress Disorder.

    PubMed

    Stock, Eileen M; Zeber, John E; McNeal, Catherine J; Banchs, Javier E; Copeland, Laurel A

    2018-04-01

    In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880). Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, p<0.01). Psychotropic medications conferring significant risks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44). Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

  12. Clinical outcome of Guillain-Barré syndrome after prolonged mechanical ventilation.

    PubMed

    van den Berg, Bianca; Storm, Eline F; Garssen, Marcel J P; Blomkwist-Markens, Patricia H; Jacobs, Bart C

    2018-04-07

    Patients with Guillain-Barré syndrome (GBS) may suffer from respiratory failure for months or longer. The aim of this study was to determine the frequency, clinical course and outcome of patients with GBS requiring prolonged mechanical ventilation (MV). Prospectively collected data from 526 patients with GBS participating in previous trials were analysed to determine the frequency and duration of prolonged MV (longer than 2 months). In addition, a cross-sectional study was conducted in patients with GBS requiring MV to determine the clinical course and long-term outcome with the ability to walk unaided as primary endpoint. In the cohort study, 145 of 526 patients with GBS (28%) required MV, including 33 (6%) patients with prolonged MV. Patients requiring prolonged MV had a lower Medical Research Council sum score and more frequent bulbar involvement and inexcitable nerves compared with shorter ventilated patients. At 6 months, 18% of patients with prolonged MV were able to walk unaided compared with 76% of patients requiring shorter MV (P<0.001). In the cross-sectional study, 63 patients requiring MV were included with a median follow-up of 11 years (range 2-44 years). Twenty-six (41%) of these patients needed prolonged MV (median 93 days, range 62-261). Fifteen (58%) of these patients were able to walk unaided at maximum follow-up and eight (31%) reached this endpoint more than 1 year after diagnosis. Prolonged ventilation in GBS is associated with poor prognosis, yet patients requiring prolonged ventilation may show slow but persistent recovery for years and even reach the ability to walk and live independently. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Mercury Report-Children's exposure to elemental mercury

    MedlinePlus

    ... gov . Mercury Background Mercury Report Additional Resources Mercury Report - Children's Exposure to Elemental Mercury Recommend on Facebook ... I limit exposure to mercury? Why was the report written? Children attending a daycare in New Jersey ...

  14. The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish Allergy Clinic.

    PubMed

    Fransson, Sara; Mosbech, Holger; Kappel, Mogens; Hjortlund, Janni; Poulsen, Lars K; Kvisselgaard, Ask D; Garvey, Lene H

    Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. To evaluate drug allergy investigations on the basis of drug provocation, including prolonged provocation. Data from adult patients investigated for drug allergy in a Danish Allergy Clinic during the period 2010 to 2014 were entered into a database. Data included clinical details and results of provocations with suspected culprit drug (for penicillins performed only in specific IgE-negative patients). If provocation was negative on first dose, treatment was continued for 3 to 10 days. A total of 1,913 provocations were done in 1,659 patients, median age 46 years, of whom 1,237 (74.6%) were females. Drugs investigated were antibiotics, 1,776 (92.8%), of which 1,590 (89.5%) were penicillins; analgesics, 59 (3.1%); local anesthetics, 33 (1.7%); and other drugs, 45 (2.4%). In total, 211 of 1,913 (11.0%) provocations were positive. Causes were antibiotics, 198 (93.8%), of which 167 (84.3%) were penicillins; analgesics, 7 (3.3%); local anesthetics, 0; and other drugs, 6 (2.8%). Only 43 (20.4%) provocations were positive on first dose, whereas 95 (45.0%) turned positive more than 3 days later. Only 11.0% of the provocations were positive. Importantly, only 1 of 5 patients tested positive on the first dose, indicating that prolonged exposure should always be considered when drug provocation is included in allergy investigations. Most provocations were with penicillins, reflecting the pattern of antibiotic use in Denmark, which differs from that in other countries, especially outside Northern Europe. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Prolongation of RBC survival in the hypophysectomized rat.

    NASA Technical Reports Server (NTRS)

    Landaw, S. A.; Bristol, S. K.

    1971-01-01

    Red blood cell (RBC) survival was prolonged in hypophysectomized rats. While the rate of random hemolysis was decreased in some hypophysectomized hosts, in all directly injected and cross-transfused hypophysectomized rat hosts, there was a significant prolongation of the phase of senescent death. In contrast, RBCs from hypophysectomized donors survived normally in normal hosts. These experiments are further evidence of a relationship between RBC aging and metabolic rate, and suggest an intimate involvement with the calorigenic hormones.

  16. QT prolongation and proarrhythmia by moxifloxacin: concordance of preclinical models in relation to clinical outcome

    PubMed Central

    Chen, Xian; Cass, Jessica D; Bradley, Jenifer A; Dahm, Corinn M; Sun, Zhuoqian; Kadyszewski, Edmund; Engwall, Michael J; Zhou, Jun

    2005-01-01

    Moxifloxacin, a fluoroquinolone antibiotic associated with QT prolongation, has been recommended as a positive control by regulatory authorities to evaluate the sensitivity of both clinical and preclinical studies to detect small but significant increases in QT interval measurements. In this study, we investigated effects of moxifloxacin on the hERG current in HEK-293 cells, electrocardiograms in conscious telemetered dogs, and repolarization parameters and arrhythmogenic potentials in the arterially perfused rabbit ventricular wedge model. Moxifloxacin inhibited the hERG current with an IC50 of 35.7 μM. In conscious telemetered dogs, moxifloxacin significantly prolonged QTc at 30 and 90 mg kg−1, with mean serum Cmax of 8.52 and 22.3 μg ml−1, respectively. In the wedge preparation, moxifloxacin produced a concentration-dependent prolongation of the action potential duration, QT interval, and the time between peak and end of the T wave, an indicator for transmural dispersion of repolarization. Phase 2 early after-depolarizations were observed in one of five experiments at 30 μM and five of five experiments at 100 μM. The arrhythmogenic potential was also concentration-dependent, and 100 μM (∼18-fold above the typical unbound Cmax exposure in clinical usage) appeared to have a high risk of inducing torsade de pointes (TdP). Our data indicated a good correlation among the concentration–response relationships in the three preclinical models and with the available clinical data. The lack of TdP report by moxifloxacin in patients without other risk factors might be attributable to its well-behaved pharmacokinetic profile and other dose-limiting effects. PMID:16158069

  17. Women's experiences of becoming a mother after prolonged labour.

    PubMed

    Nystedt, Astrid; Högberg, Ulf; Lundman, Berit

    2008-08-01

    This paper is a report of a study to explore women's experiences of becoming a mother after prolonged labour. The negativity associated with a complicated labour such as prolonged labour can lead to a struggle to become a healthy mother and could restrict the process of becoming a mother. Interviews were conducted in 2004 with 10 mothers who had been through a prolonged labour with assisted vaginal or caesarean delivery 1-3 months previously. Thematic content analysis was used. Three themes were formulated, describing women's experiences as fumbling in the dark, struggling for motherhood and achieving confidence in being a mother. The difficulties and suffering involved in becoming a mother after a prolonged labour were interpreted to be like 'fumbling in the dark'. Women experienced bodily fatigue, accompanied by feelings of illness and detachment from the child. Having the child when in this condition entailed a struggle to become a mother. In spite of these experiences and the desire to achieve confidence in being a mother, the reassurance of these women regarding their capacity for motherhood was crucial: it was central to their happiness as mothers, encouraged interaction and relationship with the child, and contributed to their adaptation to motherhood. Women experiencing prolonged labour may be comparable with the experience of and recovery from illness, which could contribute to difficulties transitioning to motherhood and limit a woman's ability to be emotionally available for the child.

  18. Symptoms of prolonged grief and posttraumatic stress following loss: A latent class analysis.

    PubMed

    Maccallum, Fiona; Bryant, Richard A

    2018-04-01

    Individuals vary in how they respond to bereavement. Those who experience poor bereavement outcomes often report symptoms from more than one diagnostic category. This study sought to identify groups of individuals who share similar patterns of prolonged grief disorder and posttraumatic stress disorder symptoms to determine whether these profiles are differentially related to negative appraisals thought to contribute to prolonged grief disorder and posttraumatic stress disorder symptomatology. Participants were 185 bereaved adults. Latent class analysis was used to identify subgroups of individuals who showed similar patterns of co-occurrence of prolonged grief disorder and posttraumatic stress disorder symptoms. Multinomial regression was used to examine the extent to which appraisal domains and sociodemographic and loss factors predicted class membership. Latent class analysis revealed three classes of participants: a low symptom group, a high prolonged grief disorder symptom group, and a high prolonged grief disorder and posttraumatic stress disorder symptom group. Membership of the prolonged grief disorder group and prolonged grief disorder and posttraumatic stress disorder group was predicted by higher mean negative self-related appraisals. Demographic and loss-related factors did not predict group membership. These findings have implications for understanding co-occurrence of prolonged grief disorder and posttraumatic stress disorder symptoms following bereavement. Findings are consistent with theoretical models highlighting the importance of negative self-related beliefs in prolonged grief disorder.

  19. Gastrografin in Prolonged Postoperative Ileus: A Double-blinded Randomized Controlled Trial.

    PubMed

    Vather, Ryash; Josephson, Rachel; Jaung, Rebekah; Kahokehr, Arman; Sammour, Tarik; Bissett, Ian

    2015-07-01

    To investigate the therapeutic value of Gastrografin in shortening duration of prolonged postoperative ileus (PPOI) after elective colorectal surgery. Gut wall edema is central to the pathogenesis of PPOI. Hyperosmotic, orally administered, water-soluble contrast media such as Gastrografin are theoretically capable of mitigating this edema. A double-blinded, placebo-controlled, randomized trial was conducted. Participants were allocated to receive 100 mL of Gastrografin (Exposure Group) or flavored distilled water (Control Group) administered enterally. Other aspects of management were standardized. Resolution of PPOI was assessed 12-hourly. Eighty patients were randomized equally, with 5 in the Exposure Group and 4 in the Control Group excluded from analysis. Participants were evenly matched at baseline. Mean duration of PPOI did not differ between Exposure and Control Groups (83.7 vs 101.3 hours; P = 0.191). When considering individual markers of PPOI resolution, Gastrografin did not affect time to resolution of nausea and vomiting (64.5 vs 74.3 hours; P = 0.404) or consumption of oral diet (75.8 vs 90.0 hours; P = 0.297). However, it accelerated time to flatus or stool (18.9 vs 32.7 hours; P = 0.047) and time to resolution of abdominal distension (52.8 vs 77.7 hours; P = 0.013). There were no significant differences between groups in nasogastric output; analgesia, antiemetic, or fluid requirement; complications; or length of stay. Gastrografin is not clinically useful in shortening an episode of PPOI characterized by upper and lower gastrointestinal symptoms. It may however be of therapeutic benefit in the subset of PPOI patients who display lower gastrointestinal symptoms exclusively after surgery.

  20. Influence of statins on distinct circulating microRNAs during prolonged aerobic exercise

    PubMed Central

    Min, Pil-Ki; Park, Joseph; Isaacs, Stephanie; Taylor, Beth A.; Thompson, Paul D.; Troyanos, Chris; D'Hemecourt, Pierre; Dyer, Sophia; Baggish, Aaron L.

    2015-01-01

    Statins exacerbate exercise-induced skeletal muscle injury. Muscle-specific microRNAs (myomiRs) increase in plasma after prolonged exercise, but the patterns of myomiRs release after statin-associated muscle injury have not been examined. We examined the relationships between statin exposure, in vitro and in vivo muscle contraction, and expression of candidate circulating myomiRs. We measured plasma levels of myomiRs, circulating microRNA-1 (c-miR-1), c-miR-133a, c-miR-206, and c-miR-499-5p from 28 statin-using and 28 nonstatin-using runners before (PRE), immediately after (FINISH), and 24 h after they ran a 42-km footrace (the 2011 Boston marathon) (POST-24). To examine these cellular-regulation myomiRs, we used contracting mouse C2C12 myotubes in culture with and without statin exposure to compare intracellular and extracellular expression of these molecules. In marathoners, c-miR-1, c-miR-133a, and c-miR-206 increased at FINISH, returned to baseline at POST-24, and were unaffected by statin use. In contrast, c-miR-499-5p was unchanged at FINISH but increased at POST-24 among statin users compared with PRE and runners who did not take statins. In cultured C2C12 myotubes, extracellular c-miR-1, c-miR-133a, and c-miR-206 were significantly increased by muscle contraction regardless of statin use. In contrast, extracellular miR-499-5p was unaffected by either isolated statin exposure or isolated carbachol exposure but it was increased when muscle contraction was combined with statin exposure. In summary, we found that statin-potentiated muscle injury during exercise is accompanied by augmented extracellular release of miR-499-5p. Thus c-miR-499-5p may serve as a biomarker of statin-potentiated muscle damage. PMID:26472872

  1. Glucocorticoid receptors and extinction retention deficits in the single prolonged stress model.

    PubMed

    Knox, D; Nault, T; Henderson, C; Liberzon, I

    2012-10-25

    Single prolonged stress (SPS) is a rodent model of post traumatic stress disorder that is comprised of serial application of restraint (r), forced swim (fs), and ether (eth) followed by a 7-day quiescent period. SPS induces extinction retention deficits and it is believed that these deficits are caused by the combined stressful effect of serial exposure to r, fs, and eth. However, this hypothesis remains untested. Neurobiological mechanisms by which SPS induces extinction retention deficits are unknown, but SPS enhances glucocorticoid receptor (GR) expression in the hippocampus, which is critical for contextual modulation of extinction retrieval. Upregulation of GRs in extinction circuits may be a mechanism by which SPS induces extinction retention deficits, but this hypothesis has not been examined. In this study, we systematically altered the stressors that constitute SPS (i.e. r, fs, eth), generating a number of partial SPS (p-SPS) groups, and observed the effects SPS and p-SPSs had on extinction retention and GR levels in the hippocampus and prefrontal cortex (PFC). PFC GRs were assayed, because regions of the PFC are critical for maintaining extinction. We predicted that only exposure to full SPS would result in extinction retention deficits and enhance hippocampal and PFC GR levels. Only exposure to full SPS induced extinction retention deficits. Hippocampal and PFC GR expression was enhanced by SPS and most p-SPSs, however hippocampal GR expression was significantly larger following the full SPS exposure than all other conditions. Our findings suggest that the combined stressful effect of serial exposure to r, fs, and eth results in extinction retention deficits. The results also suggest that simple enhancements in GR expression in the hippocampus and PFC are insufficient to result in extinction retention deficits, but raise the possibility that a threshold-enhancement in hippocampal GR expression contributes to SPS-induced extinction retention deficits

  2. Neonatal and Maternal Outcomes With Prolonged Second Stage of Labor

    PubMed Central

    Laughon, S. Katherine; Berghella, Vincenzo; Reddy, Uma M.; Sundaram, Rajeshwari; Lu, Zhaohui; Hoffman, Matthew K

    2014-01-01

    Objective To assess neonatal and maternal outcomes when when the second stage of labor was prolonged according to American College of Obstetricians and Gynecologists guidelines. Methods Electronic medical record data from a retrospective cohort (2002–2008) from 12 U.S. clinical centers (19 hospitals), including 43,810 nulliparous and 59,605 multiparous singleton deliveries ≥ 36 weeks, vertex presentation, who reached 10 cm cervical dilation were analyzed. Prolonged second stage was defined as: nulliparous women with epidural > 3 hours, without > 2 hours; multiparous women with epidural > 2 hours, without > 1 hour. Maternal and neonatal outcomes were compared and adjusted odds ratios calculated controlling for maternal race, BMI, insurance, and region. Results Prolonged second stage occurred in 9.9% and 13.9% of nulliparous and 3.1% and 5.9% of multiparous women, with and without an epidural, respectively. Vaginal delivery rates with prolonged second stage compared to within guidelines were 79.9% versus 97.9% and 87.0% versus 99.4% for nulliparous women with and without epidural, respectively, and 88.7% versus 99.7% and 96.2% versus 99.9% for multiparous women with and without epidural, respectively (P<.001 for all comparisons). Prolonged second stage was associated with increased chorioamnionitis and third-degree or fourth-degree perineal lacerations. Neonatal morbidity with prolonged second stage included sepsis in nulliparous women [with epidural: 2.6% versus 1.2% (AOR 2.08; 95%CI 1.60–2.70); without epidural: 1.8% versus 1.1% (AOR 2.34; 95%CI 1.28–4.27)]; asphyxia in nulliparous women with epidural [0.3% versus 0.1%, AOR 2.39; 95% CI 1.22–4.66]; and perinatal mortality without epidural [0.18% versus 0.04% for nulliparous women (AOR 5.92; 95% CI 1.43–24.51)], and 0.21% versus 0.03% for multiparous women (AOR 6.34; 95%CI 1.32–30.34)]. However, among the offspring of women with epidurals whose second stage was prolonged (3,533 nulliparous and 1

  3. Glucose Homeostasis During Short-term and Prolonged Exposure to High Altitudes

    PubMed Central

    Ader, Marilyn; Bergman, Richard N.

    2015-01-01

    Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease because more than 400 million people worldwide reside above 1500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and better glucose tolerance compared with those who live near sea level. There is also emerging evidence of the lower prevalence of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalence of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis. PMID:25675133

  4. Challenges and perspectives of nanoparticle exposure assessment.

    PubMed

    Lee, Ji Hyun; Moon, Min Chaul; Lee, Joon Yeob; Yu, Il Je

    2010-06-01

    Nanoparticle exposure assessment presents a unique challenge in the field of occupational and environmental health. With the commercialization of nanotechnology, exposure usually starts from the workplace and then spreads to environment and consumer exposure. This report discusses the current trends of nanoparticle exposure assessment, including the definition of nanotechnology relevant terms, essential physicochemical properties for nanomaterial characterization, current international activities related nanomaterial safety, and exposure assessment standard development for nanotechnology. Further this report describes challenges of nanoparticle exposure assessment such as background measurement, metrics of nanoparticle exposure assessment and personal sampling.

  5. Does a 'tight' hamstring predict low back pain reporting during prolonged standing?

    PubMed

    Raftry, Sean M; Marshall, Paul W M

    2012-06-01

    The purpose of this study was to investigate the relationship between hamstring passive stiffness and extensibility in asymptomatic individuals with the reporting of low back pain during 2-h prolonged standing. Twenty healthy participants with no history of low back pain (mean±SD, age 22.6±2.7 years, height 1.74±0.09 m, weight 76.2±14.8 kg). Low back pain (VAS score; mm) was continuously monitored during 2-h prolonged standing. Hamstring extensibility, passive stiffness, and stretch tolerance were measured before and after prolonged standing using an instrumented straight leg raise (iSLR). Ten participants reported a clinically relevant increase (Δ VAS>10mm) in low back pain during prolonged standing. Hamstring extensiblity (leg°(max)), passive stiffness (Nm.°(-1)), and stretch tolerance (VAS; mm) were no different between pain developers and non-pain developers. No changes in hamstring measures were observed following 2-h prolonged standing. No relationship was observed in this study between measures of hamstring extensibility and the reporting of low back pain during prolonged standing. There is no evidence to recommend hamstring extensibility interventions (i.e. passive stretching) as a means of reducing pain reporting in occupations requiring prolonged standing. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. The difficult coughing child: prolonged acute cough in children

    PubMed Central

    2013-01-01

    Cough is one of the most common symptoms that patients bring to the attention of primary care clinicians. Cough can be designated as acute (<3 weeks in duration), prolonged acute cough (3 to 8 weeks in duration) or chronic (> 8 weeks in duration). The use of the term ‘prolonged acute cough’ in a cough guideline allows a period of natural resolution to occur before further investigations are warranted. The common causes are in children with post viral or pertussis like illnesses causing the cough. Persistent bacterial bronchitis typically occurs when an initial dry acute cough due to a viral infection becomes a prolonged wet cough remaining long after the febrile illness has resolved. This cough responds to a completed course of appropriate antibiotics. PMID:23574624

  7. A Biomonitoring Framework to Support Exposure and Risk Assessments

    EPA Science Inventory

    Background - Biomonitoring is used in exposure and risk assessments to reduce uncertainties along the source-to-outcome continuum. Specifically, biomarkers can help identify exposure sources, routes, and distributions, and reflect kinetic and dynamic processes following exposure ...

  8. Prolonged QRS duration on surface electrocardiogram is associated with left ventricular restrictive filling pattern

    PubMed Central

    Erdoğan, Turan; Durakoğlugil, Murtaza Emre; Çiçek, Yüksel; Çetin, Mustafa; Duman, Hakan; Şatiroğlu, Ömer; Çelik, Şükrü

    2017-01-01

    Background Prolonged QRS duration is associated with decreased left ventricular (LV) systolic function. However, the relation between LV restrictive filling pattern (RFP) and QRS duration has not been investigated yet. The purpose of our study was to assess this relationship. Methods We analyzed standard 12-lead surface electrocardiogram (ECG) of 155 consecutive patients. Mitral inflow and septal tissue velocities were obtained using the apical 4-chamber view with pulsed Doppler echocardiography. Patients were divided into 2 groups according to measured deceleration time (DT): restrictive (with DT ≤130 ms) or non-restrictive (with DT >130 ms). Results QRS duration was significantly longer in the restrictive group than in the non-restrictive group (0.101 vs. 0.090 s, p < 0.0001). QRS duration of >0.10 s was highly specific (82.6%), but modestly sensitive (64.7%), for the prediction of LV RFP. Multivariate analyses demonstrated that E/A ratio, peak E, peak A, septal e’, and a’ velocities were significantly associated with RFP. Conclusions Prolonged QRS duration (>0.10 s) obtained from a standard resting 12-lead ECG is associated with LV RFP. However, the relationship of QRS duration with RFP was not independent of echocardiographic parameters. PMID:28932490

  9. Prolonged partial epilepsy: a case report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilson, M.A.

    1980-11-01

    The case study of a patient with prolonged partial epilepsy is presented. There was a discrepancy between the extent of the abnormality seen on the radionuclide angiogram and that seen on the static brain scan.

  10. Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1.

    PubMed

    Xu, Yanli; Xu, Shan; Cai, Yueqin; Liu, Luming

    2015-01-01

    The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ) on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1) was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08-50 mg/mL) of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine). mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L) in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option.

  11. Prolongation structures of nonlinear evolution equations. II

    NASA Technical Reports Server (NTRS)

    Estabrook, F. B.; Wahlquist, H. D.

    1976-01-01

    The prolongation structure of a closed ideal of exterior differential forms is further discussed, and its use illustrated by application to an ideal (in six dimensions) representing the cubically nonlinear Schroedinger equation. The prolongation structure in this case is explicitly given, and recurrence relations derived which support the conjecture that the structure is open - i.e., does not terminate as a set of structure relations of a finite-dimensional Lie group. We introduce the use of multiple pseudopotentials to generate multiple Baecklund transformation, and derive the double Baecklund transformation. This symmetric transformation concisely expresses the (usually conjectured) theorem of permutability, which must consequently apply to all solutions irrespective of asymptotic constraints.

  12. Epidemic gasoline exposures following Hurricane Sandy.

    PubMed

    Kim, Hong K; Takematsu, Mai; Biary, Rana; Williams, Nicholas; Hoffman, Robert S; Smith, Silas W

    2013-12-01

    Major adverse climatic events (MACEs) in heavily-populated areas can inflict severe damage to infrastructure, disrupting essential municipal and commercial services. Compromised health care delivery systems and limited utilities such as electricity, heating, potable water, sanitation, and housing, place populations in disaster areas at risk of toxic exposures. Hurricane Sandy made landfall on October 29, 2012 and caused severe infrastructure damage in heavily-populated areas. The prolonged electrical outage and damage to oil refineries caused a gasoline shortage and rationing unseen in the USA since the 1970s. This study explored gasoline exposures and clinical outcomes in the aftermath of Hurricane Sandy. Prospectively collected, regional poison control center (PCC) data regarding gasoline exposure cases from October 29, 2012 (hurricane landfall) through November 28, 2012 were reviewed and compared to the previous four years. The trends of gasoline exposures, exposure type, severity of clinical outcome, and hospital referral rates were assessed. Two-hundred and eighty-three gasoline exposures were identified, representing an 18 to 283-fold increase over the previous four years. The leading exposure route was siphoning (53.4%). Men comprised 83.0% of exposures; 91.9% were older than 20 years of age. Of 273 home-based calls, 88.7% were managed on site. Asymptomatic exposures occurred in 61.5% of the cases. However, minor and moderate toxic effects occurred in 12.4% and 3.5% of cases, respectively. Gastrointestinal (24.4%) and pulmonary (8.4%) symptoms predominated. No major outcomes or deaths were reported. Hurricane Sandy significantly increased gasoline exposures. While the majority of exposures were managed at home with minimum clinical toxicity, some patients experienced more severe symptoms. Disaster plans should incorporate public health messaging and regional PCCs for public health promotion and toxicological surveillance.

  13. IRE1α pathway of endoplasmic reticulum stress induces neuronal apoptosis in the locus coeruleus of rats under single prolonged stress.

    PubMed

    Zhao, Wei; Han, Fang; Shi, Yuxiu

    2016-08-01

    Our previous studies have shown evidence of endoplasmic reticulum (ER) stress-induced apoptosis in the hippocampus and mPFC in an animal model of post- traumatic stress disorder (PTSD). Inositol-requiring enzyme 1α (IRE1α) and its downstream molecule X-box binding protein 1 (XBP1) play key roles in the ER-related apoptosis pathway. Dysregulation of the locus coeruleus (LC) has been reported to contribute to cognitive and/or arousal impairments associated with PTSD. The aim of the present study was to explore the role of IRE1α pathway in neuronal apoptosis in the LC of rat models of PTSD. We used an acute exposure to prolonged stress (single prolonged stress, SPS) to model PTSD in rats and examined the effects related to the IRE1α pathway. Neuronal apoptosis in LC was detected by transmission electron microscopy and TUNEL staining. The results showed that the level of LC neuronal apoptosis was markedly increased after SPS. SPS exposure triggered IRE1α pathway, as evidenced by the increased activity of IRE1α, specific splicing of XBP1, and up-regulated expression of binding immunoglobulin protein/78kDa glucose-regulated protein (BiP/GRP78), and C/EBP-homologous protein (CHOP). Treatment with STF-083010, an IRE1α RNase-specific inhibitor, successfully attenuated the above changes. These results indicate that excessive activation of the ER stress-associated IRE1α pathway is involved in LC neuronal apoptosis induced by SPS exposure; this may be a crucial mechanism of the pathogenesis of PTSD. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Laboratory electron exposure of TSS-1 thermal control coating

    NASA Technical Reports Server (NTRS)

    Vaughn, J. A.; Mccollum, M.; Carruth, M. R., Jr.

    1995-01-01

    RM400, a conductive thermal control coating, was developed for use on the exterior shell of the tethered satellite. Testing was performed by the Engineering Physics Division to quantify effects of the space environment on this coating and its conductive and optical properties. Included in this testing was exposure of RM400 to electrons with energies ranging from 0.1 to 1 keV, to simulate electrons accelerated from the ambient space plasma when the tethered satellite is fully deployed. During this testing, the coating was found to luminesce, and a prolonged exposure of the coating to high-energy electrons caused the coating to darken. This report describes the tests done to quantify the degradation of the thermal control properties caused by electron exposure and to measure the luminescence as a function of electron energy and current density to the satellite.

  15. Carry-over fluency induced by extreme prolongations: A new behavioral paradigm.

    PubMed

    Briley, P M; Barnes, M P; Kalinowski, J S

    2016-04-01

    Extreme prolongations, which can be generated via extreme delayed auditory feedback (DAF) (e.g., 250-500 ms) or mediated cognitively with timing applications (e.g., analog stopwatch) at 2 s per syllable, have long been behavioral techniques used to inhibit stuttering. Some therapies have used this rate solely to establish initial fluency, while others use extremely slowed speech to establish fluency and add other strategic techniques such as easy onsets and diaphragmatic breathing. Extreme prolongations generate effective, efficient, and immediate forward flowing fluent speech, removing the signature behaviors of discrete stuttering (i.e., syllable repetitions and audible and inaudible postural fixations). Prolonged use of extreme prolongations establishes carry-over fluency, which is spontaneous, effortless speech absent of most, if not all, overt and covert manifestations of stuttering. The creation of this immediate fluency and the immense potential of extreme prolongations to generate long periods of carry-over fluency have been overlooked by researchers and clinicians alike. Clinicians depart from these longer prolongation durations as they attempt to achieve the same fluent results at a near normal rate of speech. Clinicians assume they are re-teaching fluency and slow rates will give rise to more normal rates with less control, but without carry-over fluency, controls and cognitive mediation are always needed for the inherently unstable speech systems of persons who stutter to experience fluent speech. The assumption being that the speech system is untenable without some level of cognitive and motoric monitoring that is always necessary. The goal is omnipresent "near normal rate sounding fluency" with continuous mediation via cognitive and motoric processes. This pursuit of "normal sounding fluency" continues despite ever-present relapse. Relapse has become so common that acceptance of stuttering is the new therapy modality because relapse has come to be

  16. Surface alpha backgrounds from plate-out of radon progeny

    NASA Astrophysics Data System (ADS)

    Perumpilly, Gopakumar; Guiseppe, Vincente

    2012-03-01

    Low-background detectors operating underground aim for unprecedented low levels of radioactive backgrounds. Although the radioactive decays of airborne radon (particularly Rn-222) and its subsequent daughters present in an experiment are potential backgrounds, more troublesome is the deposition of radon daughters on detector materials. Exposure to radon at any stage of assembly of an experiment can result in surface contamination by daughters supported by the long half life (22 y) of Pb-210 on sensitive locations of a detector. We have developed a model of the radon progeny implantation using Geant4 simulations based on the low energy nuclear recoil process. We explore the alpha decays from implanted progeny on a Ge crystal as potential backgrounds for a neutrinoless double-beta decay experiment. Results of the simulations validated with alpha spectrum measurement of plate-out samples will be presented.

  17. IN-HOME EXPOSURE THERAPY FOR VETERANS WITH POST TRAUMATIC STRESS DISORDER

    DTIC Science & Technology

    2016-10-01

    study protocol. 5 Our treatment clinicians are providing the manual-guided evidence - based PE PTSD intervention. Therapists attend a weekly PE...with PTSD confirming the noninferiority of using CVT to deliver an evidence - based treatment (EBT) for PTSD, Cognitive Processing Therapy (CPT; Resick...g. Treatment clinicians will conduct a manual-guided evidence based PTSD intervention, Prolonged Exposure Therapy (PE), with approximately 175

  18. Developmental and neurobehavioral effects of perinatal exposure to polychlorinated biphenyls in mice.

    PubMed

    Sugawara, Norio; Nakai, Kunihiko; Nakamura, Tomoyuki; Ohba, Takashi; Suzuki, Keita; Kameo, Satomi; Satoh, Chieko; Satoh, Hiroshi

    2006-05-01

    Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning.

  19. Identifying QT prolongation from ECG impressions using a general-purpose Natural Language Processor

    PubMed Central

    Denny, Joshua C.; Miller, Randolph A.; Waitman, Lemuel Russell; Arrieta, Mark; Peterson, Joshua F.

    2009-01-01

    Objective Typically detected via electrocardiograms (ECGs), QT interval prolongation is a known risk factor for sudden cardiac death. Since medications can promote or exacerbate the condition, detection of QT interval prolongation is important for clinical decision support. We investigated the accuracy of natural language processing (NLP) for identifying QT prolongation from cardiologist-generated, free-text ECG impressions compared to corrected QT (QTc) thresholds reported by ECG machines. Methods After integrating negation detection to a locally-developed natural language processor, the KnowledgeMap concept identifier, we evaluated NLP-based detection of QT prolongation compared to the calculated QTc on a set of 44,318 ECGs obtained from hospitalized patients. We also created a string query using regular expressions to identify QT prolongation. We calculated sensitivity and specificity of the methods using manual physician review of the cardiologist-generated reports as the gold standard. To investigate causes of “false positive” calculated QTc, we manually reviewed randomly selected ECGs with a long calculated QTc but no mention of QT prolongation. Separately, we validated the performance of the negation detection algorithm on 5,000 manually-categorized ECG phrases for any medical concept (not limited to QT prolongation) prior to developing the NLP query for QT prolongation. Results The NLP query for QT prolongation correctly identified 2,364 of 2,373 ECGs with QT prolongation with a sensitivity of 0.996 and a positive predictive value of 1.000. There were no false positives. The regular expression query had a sensitivity of 0.999 and positive predictive value of 0.982. In contrast, the positive predictive value of common QTc thresholds derived from ECG machines was 0.07–0.25 with corresponding sensitivities of 0.994–0.046. The negation detection algorithm had a recall of 0.973 and precision of 0.982 for 10,490 concepts found within ECG impressions

  20. Physiological consequences of rapid or prolonged aircraft decompression: evaluation using a human respiratory model.

    PubMed

    Wolf, Matthew

    2014-04-01

    Aircraft passengers and crew may be subjected to rapid or prolonged decompression to high cabin altitude when an aircraft develops a hole in the fuselage. The accepted measure of neurological damage due to the hypobaric hypoxia produced is the subjective 'time of useful consciousness' (TUC) measure, which is appropriate for pilots and crew who perform their given tasks, however, TUC is measured under conditions different than the decompression scenarios that passengers undergo in today's aircraft. Ernsting proposed that prolonged exposure to alveolar O2 pressures less than 30 mmHg (P30) causes neurological damage. The current study proposes that a critical value of arterial O2 saturation of 70% (S70) can be used in place of P30 and that this physiological measure is more suited for determination of hypobaric hypoxia in passengers. The study shows the equivalence of model-predicted P30 and S70 values in the Ernsting-decompression scenarios. The model is also used to predict values of these physiological measures in actual aircraft-decompression scenarios. The model can be used by others to quantitatively predict the degree of hypobaric hypoxia for virtually any kind of decompression scenario, including those where supplemental O2 is used. Use of this tool avoids the prohibitive costs of human-subject testing for new aircraft and the potential danger inherent in such tests.

  1. Biological effects from electromagnetic field exposure and public exposure standards.

    PubMed

    Hardell, Lennart; Sage, Cindy

    2008-02-01

    During recent years there has been increasing public concern on potential health risks from power-frequency fields (extremely low frequency electromagnetic fields; ELF) and from radiofrequency/microwave radiation emissions (RF) from wireless communications. Non-thermal (low-intensity) biological effects have not been considered for regulation of microwave exposure, although numerous scientific reports indicate such effects. The BioInitiative Report is based on an international research and public policy initiative to give an overview of what is known of biological effects that occur at low-intensity electromagnetic fields (EMFs) exposure. Health endpoints reported to be associated with ELF and/or RF include childhood leukaemia, brain tumours, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, breast cancer, miscarriage and some cardiovascular effects. The BioInitiative Report concluded that a reasonable suspicion of risk exists based on clear evidence of bioeffects at environmentally relevant levels, which, with prolonged exposures may reasonably be presumed to result in health impacts. Regarding ELF a new lower public safety limit for habitable space adjacent to all new or upgraded power lines and for all other new constructions should be applied. A new lower limit should also be used for existing habitable space for children and/or women who are pregnant. A precautionary limit should be adopted for outdoor, cumulative RF exposure and for cumulative indoor RF fields with considerably lower limits than existing guidelines, see the BioInitiative Report. The current guidelines for the US and European microwave exposure from mobile phones, for the brain are 1.6 W/Kg and 2 W/Kg, respectively. Since use of mobile phones is associated with an increased risk for brain tumour after 10 years, a new biologically based guideline is warranted. Other health impacts associated with exposure to

  2. Prolonged fasting activates Nrf2 in post-weaned elephant seals

    PubMed Central

    Vázquez-Medina, José Pablo; Soñanez-Organis, José G.; Rodriguez, Ruben; Viscarra, Jose A.; Nishiyama, Akira; Crocker, Daniel E.; Ortiz, Rudy M.

    2013-01-01

    SUMMARY Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin–angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 167% at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 5000% and 250% higher at week 7 than at week 1. Phosphorylation of Smad2, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 430% at week 7, while Nox4 protein expression, which can activate Nrf2, was 170% higher at week 7 than at week 1. These results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. The results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals. PMID:23619404

  3. Prolonged fasting activates Nrf2 in post-weaned elephant seals.

    PubMed

    Vázquez-Medina, José Pablo; Soñanez-Organis, José G; Rodriguez, Ruben; Viscarra, Jose A; Nishiyama, Akira; Crocker, Daniel E; Ortiz, Rudy M

    2013-08-01

    Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin-angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 167% at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 5000% and 250% higher at week 7 than at week 1. Phosphorylation of Smad2, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 430% at week 7, while Nox4 protein expression, which can activate Nrf2, was 170% higher at week 7 than at week 1. These results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. The results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals.

  4. AORN Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings.

    PubMed

    Hughes, Nancy L; Nelson, Audrey; Matz, Mary W; Lloyd, John

    2011-06-01

    Prolonged standing during surgical procedures poses a high risk of causing musculoskeletal disorders, including back, leg, and foot pain, which can be chronic or acute in nature. Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings provides recommendations for relieving the strain of prolonged standing, including the use of antifatigue mats, supportive footwear, and sit/stand stools, that are based on well-accepted ergonomic safety concepts, current research, and access to new and emerging technology. Published by Elsevier Inc.

  5. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

    PubMed Central

    Berde, Charles B.; Athiraman, Umeshkumar; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel; Bognet, Christina

    2011-01-01

    Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL) solutions, with or without epinephrine 5 µg/mL (1:200,000) in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001) or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001). Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia. PMID:22363247

  6. Tetrodotoxin-bupivacaine-epinephrine combinations for prolonged local anesthesia.

    PubMed

    Berde, Charles B; Athiraman, Umeshkumar; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel; Bognet, Christina

    2011-12-01

    Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL) solutions, with or without epinephrine 5 µg/mL (1:200,000) in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001) or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001). Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

  7. Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

    PubMed

    Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

    2016-05-01

    In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. 21-cm lensing and the cold spot in the cosmic microwave background.

    PubMed

    Kovetz, Ely D; Kamionkowski, Marc

    2013-04-26

    An extremely large void and a cosmic texture are two possible explanations for the cold spot seen in the cosmic microwave background. We investigate how well these two hypotheses can be tested with weak lensing of 21-cm fluctuations from the epoch of reionization measured with the Square Kilometer Array. While the void explanation for the cold spot can be tested with Square Kilometer Array, given enough observation time, the texture scenario requires significantly prolonged observations, at the highest frequencies that correspond to the epoch of reionization, over the field of view containing the cold spot.

  9. Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days.

    PubMed

    Starokozhko, Viktoriia; Vatakuti, Suresh; Schievink, Bauke; Merema, Marjolijn T; Asplund, Annika; Synnergren, Jane; Aspegren, Anders; Groothuis, Geny M M

    2017-05-01

    Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and function of hPCLS to 5 days of incubation. hPCLS were incubated in two media developed for long-term culture of hepatocytes, RegeneMed ® , and Cellartis ® , and in the standard medium WME. Maintenance of phase I and II metabolism was studied both on gene expression as well as functional level using a mixture of CYP isoform-specific substrates. Albumin synthesis, morphological integrity, and glycogen storage was assessed, and gene expression was studied by transcriptomic analysis using microarrays with a focus on genes involved in drug metabolism, transport and toxicity. The data show that hPCLS retain their viability and functionality during 5 days of incubation in Cellartis ® medium. Albumin synthesis as well as the activity and gene expression of phase I and II metabolic enzymes did not decline during 120-h incubation in Cellartis ® medium, with CYP2C9 activity as the only exception. Glycogen storage and morphological integrity were maintained. Moreover, gene expression changes in hPCLS during incubation were limited and mostly related to cytoskeleton remodeling, fibrosis, and moderate oxidative stress. The expression of genes involved in drug transport, which is an important factor in determining the intracellular xenobiotic exposure, was also unchanged. Therefore, we conclude that hPCLS cultured in Cellartis ® medium are a valuable human ex vivo model for toxicological and pharmacological studies that require prolonged xenobiotic exposure.

  10. Binge-pattern cocaine administration causes long-lasting behavioral hyperarousal but does not enhance vulnerability to single prolonged stress in rats.

    PubMed

    Lisieski, Michael J; Perrine, Shane A

    2017-11-01

    Cocaine use disorder and post-traumatic stress disorder (PTSD) commonly co-occur. This could be due to vulnerability to post-traumatic symptoms conferred by previous exposure to cocaine. Therefore, we combined chronic binge-pattern cocaine with a model of psychological trauma (single prolonged stress) to determine whether the behavioral effects of psychological trauma are enhanced in cocaine-sensitized individuals. Adult male Sprague Dawley rats received 14 days of cocaine (15mg/kg/injection) or saline in a binge pattern (3 injections per day, 1h apart). Seven days after the last injection animals were exposed to traumatic stress or a control procedure. Seven days after stress, activity and anxiety-like behaviors were measured. Binge-pattern cocaine increased locomotor activity in the open field and elevated plus maze, and both cocaine and SPS exposure increased the rapidity with which rats moved through grooming sequences. Neither binge-pattern cocaine nor SPS increased anxiety-like behaviors, and no interactions were found between binge-pattern cocaine exposure and SPS exposure. A behavioral phenotype categorization approach demonstrated that cocaine-exposed groups expressed a high incidence of hyperactivity-like symptoms. These results suggest that binge-pattern cocaine exposure causes a long-lasting hyper-exploratory phenotype but does not make individuals more vulnerable to a later traumatic stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Prolonged carotid sinus reflex is a risk factor for contrast-induced nephropathy following carotid artery stenting.

    PubMed

    Kato, T; Sakai, H; Tsujimoto, M; Nishimura, Y

    2011-03-01

    Although many studies have demonstrated that CIN is associated with in-hospital and long-term mortality, the incidence of CIN following CAS is unclear. We investigated the incidence of CIN, defined as an increase from a baseline creatinine value of at least 0.5 mg/dL or 25% within 72 hours of contrast administration, and we also examined renal function in the late phase after CAS. We examined 80 patients who underwent CAS between April 2005 and December 2009. Clinical background, laboratory data, contrast volume, and clinical course were collected and analyzed. The incidence of CIN was 8.8% (7/80), and no patients required hemodialysis. In the group that developed CIN, prolonged CSR after CAS was found in 57.1% (4/7) of cases; this incidence differed significantly (P = .001) from that in the group without development of CIN. Neither preoperative renal function, contrast volume, nor history was related to the incidence of CIN, while on multivariate analysis, prolonged CSR was found to be an independent risk factor for CIN. The incidence of elevation in creatinine values at 6 months after CAS was 8.2% (6/73). All patients who developed delayed renal impairment had pre-existing CKD; this finding differed significantly (P = .04) from that in the group without development of delayed renal impairment. Because patients who develop prolonged CSR after CAS are at increased risk of perioperative major adverse clinical events including CIN, patients at high risk for this condition should be carefully managed to prevent increased morbidity and mortality.

  12. Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

    PubMed Central

    Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

    2015-01-01

    Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and

  13. Ibrutinib does not prolong the corrected QT interval in healthy subjects: results from a thorough QT study.

    PubMed

    de Jong, Jan; Hellemans, Peter; Jiao, James Juhui; Huang, Yuhan; Mesens, Sofie; Sukbuntherng, Juthamas; Ouellet, Daniele

    2017-12-01

    Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. Part 1 used an open-label, two-period sequential design to assess the safety and pharmacokinetics of single doses of ibrutinib 840 and 1680 mg in eight subjects. Part 2 was a randomized, placebo- and positive (moxifloxacin)-controlled, double-blind, single dose, four-way cross-over study to assess the effect of ibrutinib (840 and 1680 mg) on QT/QTc interval. 64 healthy subjects were planned to be enrolled. Baseline-adjusted QT (QTc) intervals for ibrutinib and moxifloxacin (assay sensitivity) were compared to placebo using linear mixed-effect model. A concentration-QTc analysis was also conducted. No clinically relevant safety observations were noted in Part 1. During Part 2, one subject experienced Grade 4 ALT/AST elevations with ibrutinib 1680 mg, leading to study termination and limiting the enrollment to 20 subjects. Ibrutinib demonstrated dose-dependent increases in exposure. The upper bounds of the 90% CIs for the mean difference in change from baseline in QTc between ibrutinib and placebo were < 10 ms at all timepoints and at supratherapeutic C max . Moxifloxacin showed the anticipated QTc effect, confirming assay sensitivity despite the early study termination. Ibrutinib caused a concentration-dependent mild shortening of QTc and mild PR prolongation, but these effects were not considered clinically meaningful. Therapeutic and supratherapeutic concentrations of ibrutinib do not prolong the QTc interval. CLINICALTRIALS.GOV: NCT02271438.

  14. Exercise as a countermeasure for physiological adaptation to prolonged spaceflight

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.

    1996-01-01

    Exercise represents the primary countermeasure used during spaceflight to maintain or restore maximal aerobic capacity (VO2max), musculoskeletal structure, and orthostatic function. However, no single exercise or combination of prescriptions has proven entirely effective in restoring cardiovascular and musculoskeletal functions to preflight levels following prolonged spaceflight. As human spaceflight exposures increase in duration, assessment and development of various effective exercise-based protective procedures become paramount. This must involve improvement in specific countermeasure prescription as well as development of additional approaches that will allow space travelers greater flexibility and medical safety during long flights. Effective exercise prescription will be based on identification of basic physiological stimuli that maintain normal function in terrestrial gravity and understanding of how specific combinations of exercise characteristics e.g., duration, frequency, intensity, mode) can mimic these stimuli and affect the overall process of adaptation to microgravity. This can be accomplished only with greater emphasis of research on ground-based experiments. Future attention must be directed to improving exercise compliance while minimizing both crew time and the impact of the exercise on life-support resources.

  15. Physiology Of Prolonged Bed Rest

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.

    1991-01-01

    Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

  16. Weight Gain and Obesity in Infants and Young Children Exposed to Prolonged Antibiotic Prophylaxis.

    PubMed

    Edmonson, M Bruce; Eickhoff, Jens C

    2017-02-01

    An association between antibiotic use and excessive weight gain or obesity in healthy infants and young children has been reported, but evidence is inconsistent and based on observational studies of growth in relation to incidental antibiotic exposures. To evaluate whether prolonged antibiotic exposure is associated with weight gain in children participating in a clinical trial of antibiotic prophylaxis to prevent recurrent urinary tract infection. Secondary analysis of data from the Randomized Intervention for Children With Vesicoureteral Reflux Study, a 2-year randomized clinical trial that enrolled participants from 2007 to 2011. All 607 children who were randomized to receive antibiotic (n = 302) or placebo (n = 305) were included. Children with urinary tract anomalies, premature birth, or major comorbidities were excluded from participation. Trimethoprim-sulfamethoxazole or placebo taken orally, once daily, for 2 years. Weight gain as measured by change in weight-for-age z score from baseline to the end-of-study visit at 24 months. Secondary outcomes included weight gain at 6, 12, and 18 months and the prevalence of overweight or obesity at 24 months. Participants had a median age of 12 months (range, 2-71 months) and 558 of 607 (91.9%) were female. Anthropometric data were complete at the 24-month visit for 428 children (214 in the trimethoprim-sulfamethoxazole group and 214 in the placebo group). Weight gain in the trimethoprim-sulfamethoxazole group and the placebo group was similar (mean [SD] change in weight-for-age z score: +0.14 [0.83] and +0.18 [0.85], respectively; difference, -0.04 [95% CI, -0.19 to 0.12]; P = .65). There was no significant difference in weight gain at 6, 12, or 18 months or in the prevalence of overweight or obesity at 24 months (24.8% vs 25.7%; P = .82). Subgroup analyses showed no significant interaction between weight gain effect and age, sex, history of breastfeeding, prior antibiotic use, adherence to study

  17. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

    PubMed

    Esaiassen, Eirin; Fjalstad, Jon Widding; Juvet, Lene Kristine; van den Anker, John N; Klingenberg, Claus

    2017-07-01

    To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death. Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model. We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported. Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Prolonging life: legal, ethical, and social dilemmas.

    PubMed

    Paulson, Steve; Comfort, Christopher P; Lee, Barbara Coombs; Shemie, Sam; Solomon, Mildred Z

    2014-11-01

    The ability of modern medicine to prolong life has raised a variety of difficult legal, ethical, and social issues on which reasonable minds can differ. Among these are the morality of euthanasia in cases of deep coma or irreversible injury, as well as the Dead Donor Rule with respect to organ harvesting and transplants. As science continues to refine and develop lifesaving technologies, questions remain as to how much medical effort and financial resources should be expended to prolong the lives of patients suspended between life and death. At what point should death be considered irreversible? What criteria should be used to determine when to withhold or withdraw life-prolonging treatments in cases of severe brain damage and terminal illness? To explore these complex dilemmas, Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion panel. Pediatrician Sam Shemie, hospice medical director Christopher P. Comfort, bioethicist Mildred Z. Solomon, and attorney Barbara Coombs Lee examined the underlying assumptions and considerations that ultimately shape individual and societal decisions surrounding these issues. The following is an edited transcript of the discussion that occurred November 12, 2013, 7:00-8:30 PM, at the New York Academy of Sciences in New York City. © 2014 New York Academy of Sciences.

  19. A clinical prediction model for prolonged air leak after pulmonary resection.

    PubMed

    Attaar, Adam; Winger, Daniel G; Luketich, James D; Schuchert, Matthew J; Sarkaria, Inderpal S; Christie, Neil A; Nason, Katie S

    2017-03-01

    Prolonged air leak increases costs and worsens outcomes after pulmonary resection. We aimed to develop a clinical prediction tool for prolonged air leak using pretreatment and intraoperative variables. Patients who underwent pulmonary resection for lung cancer/nodules (from January 2009 to June 2014) were stratified by prolonged parenchymal air leak (>5 days). Using backward stepwise logistic regression with bootstrap resampling for internal validation, candidate variables were identified and a nomogram risk calculator was developed. A total of 2317 patients underwent pulmonary resection for lung cancer/nodules. Prolonged air leak (8.6%, n = 200) was associated with significantly longer hospital stay (median 10 vs 4 days; P < .001). Final model variables associated with increased risk included low percent forced expiratory volume in 1 second, smoking history, bilobectomy, higher annual surgeon caseload, previous chest surgery, Zubrod score >2, and interaction terms for right-sided thoracotomy and wedge resection by thoracotomy. Wedge resection, higher body mass index, and unmeasured percent forced expiratory volume in 1 second were protective. Derived nomogram discriminatory accuracy was 76% (95% confidence interval [CI], 0.72-0.79) and facilitated patient stratification into low-, intermediate- and high-risk groups with monotonic increase in observed prolonged air leaks (2.0%, 8.9%, and 19.2%, respectively; P < .001). Patients at intermediate and high risk were 4.80 times (95% CI, 2.86-8.07) and 11.86 times (95% CI, 7.21-19.52) more likely to have prolonged air leak compared with patients at low risk. Using readily available candidate variables, our nomogram predicts increasing risk of prolonged air leak with good discriminatory ability. Risk stratification can support surgical decision making, and help initiate proactive, patient-specific surgical management. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc

  20. A New Approach to Study Properties of Isolated Predipocytes Following In Vivo Exposure to Hypoxia

    NASA Astrophysics Data System (ADS)

    Chowdhury, Helena H.; Velebit Markovic, Jelena; Radic, Natasa; Francic, Vito; Mekjavic, Igor B.; Eiken, Ola; Zorec, Robert

    2013-02-01

    In the present study we developed a novel approach to study the properties of isolated human preadipocytes from subjects exposed to conditions of hypoxia equivalent to an altitude of 4000 m. By using confocal microscopy we studied the expression of dipeptidyl peptidase 4 (DPP4) in preadipocytes from adult normal-weight males. DPP4 is a transmembrane glycoprotein with enzymatic activity that cleaves N-terminal dipeptides from a diverse range of substrates. The activity of DPP4 is implicated in immune response as well as in glucose homeostasis. To gain insights into the pathophysiological role of DPP4 in insulin resistance we here explored DPP4 expression during prolonged exposure to hypoxia, an experimental model of obesity onset. We used here a rapid method to isolate cells from biopsies and immunolabelled them with antibodies. Then cells were prepared for the analysis with confocal microscopy. The results show that a prolonged exposure to hypoxic environment appears to increases the expression of DPP4 on preadipocytes.

  1. Wild mushroom exposures in Florida, 2003-2007.

    PubMed

    Kintziger, Kristina W; Mulay, Prakash; Watkins, Sharon; Schauben, Jay; Weisman, Richard; Lewis-Younger, Cynthia; Blackmore, Carina

    2011-01-01

    Exposure to wild mushrooms can lead to serious illness and death. However, there is little information on the epidemiology of mushroom exposures nationwide, as there is no specific surveillance for this outcome. We described mushroom exposures in Florida using available data sources. We performed a population-based study of mushroom exposure calls to the Florida Poison Information Center Network (FPICN) and cases of mushroom poisoning reported in hospital inpatient and emergency department (ED) data from 2003 through 2007. There were 1,538 unduplicated mushroom exposures reported during this period, including 1,355 exposure calls and 428 poisoning cases. Most exposures reported to FPICN occurred in children ≤6 years of age (45%) and males (64%), and most were unintentional ingestions (60%). Many exposures resulted in no effect (35%), although 21% reported mild symptoms that resolved rapidly, 23% reported prolonged/systemic (moderate) symptoms, and 1% reported life-threatening effects. Most calls occurred when in or en route to a health-care facility (43%). More than 71% of poisonings identified in hospital records were managed in an ED, and most occurred in young adults 16-25 years of age (49%), children ≤6 years of age (21%), adults >25 years of age (21%), and males (70%). No deaths were reported. Combined, these data were useful for describing mushroom exposures. Most exposures occurred in males and in young children (≤6 years of age) and young adults (16-25 years of age), with 78% resulting in contact with a health-care facility. Education should target parents of young children-especially during summer, when mushrooms are more abundant-and young adults who are likely experimenting with mushrooms for their potential hallucinogenic properties.

  2. Chronic Restraint Stress after Injury and Shock is Associated with Persistent Anemia despite Prolonged Elevation in Erythropoietin Levels

    PubMed Central

    Bible, Letitia E.; Pasupuleti, Latha V.; Gore, Amy V.; Sifri, Ziad C.; Kannan, Kolenkode B.; Mohr, Alicia M.

    2015-01-01

    Background Following severe traumatic injury, critically ill patients have a prolonged hypercatacholamine state that is associated with bone marrow (BM) dysfunction and persistent anemia. However, current animal models of injury and shock result in a transient anemia. Daily restraint stress (CS) has been shown to increase catecholamines. We hypothesize that adding CS following injury or injury and shock in rats will prolong the hypercatecholaminemia, and prolong the initial anemia, despite elevated erythropoietin levels. Methods Male Sprague-Dawley Rats (N=6–8/group) underwent lung contusion (LC) or combined lung contusion/hemorrhagic shock (LCHS) followed by six days of chronic stress (CS). CS consisted of a two hour restraint period interrupted with repositioning and alarms every 30 minutes. At seven days, urine was assessed for norepinephrine (NE) levels, blood for erythropoietin (EPO) and hemoglobin (Hgb), and BM for erythroid progenitor growth. Results Animals undergoing LC or combined LCHS predictably recovered by day seven; urine NE, EPO and Hgb levels were normal. The addition of CS to LC and LCHS models was associated with a significant elevation in NE on day six. The addition of CS to LC led to a persistent 20–25% decrease in the growth of BM HPCs. These findings were further exaggerated when CS was added following LCHS, resulting in a 20–40% reduction in BM erythroid progenitor colony growth and a 20% decrease in Hgb when compared to LCHS alone. Conclusions Exposing injured animals to CS results in prolonged elevation of norepinephrine and erythropoietin which is associated with worsening BM erythroid function and persistent anemia. Chronic restraint stress following injury and shock provides a clinically relevant model to further evaluate persistent injury-associated anemia seen in critically ill trauma patients. Furthermore, alleviating chronic stress after severe injury is a potential therapeutic target to improve BM dysfunction and anemia. PMID

  3. Cardiovascular drugs inducing QT prolongation: facts and evidence.

    PubMed

    Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

    2010-01-01

    Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

  4. Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

    NASA Technical Reports Server (NTRS)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2017-01-01

    Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative

  5. Socio-demographic patterns of posttraumatic stress disorder in Medellin, Colombia and the context of lifetime trauma exposure

    PubMed Central

    Gaviria, Silvia Lucia; Espinola, Maria; Restrepo, Diana; Lotero, Juliana; Berbesi, Dedsy Y.; Sierra, Gloria Maria; Chaskel, Roberto; Espinel, Zelde; Shultz, James M.

    2016-01-01

    ABSTRACT Colombia, South America is currently transitioning to post-conflict status following 6 decades of armed conflict. The population has experienced extensive exposures to potentially traumatic events throughout the lifespan. Sources of trauma exposure include the prolonged armed insurgency, narco-trafficking violence, urban gang violence, violent actions of criminal bands, intra-familial violence, gender-based violence, and sex trafficking. Exposure to potentially traumatic events is related to a variety of psychiatric outcomes, in particular, posttraumatic stress disorder. Given this context of lifetime trauma exposure, socio-demographic patterns of posttraumatic stress disorder were explored in a sample of residents of Medellin, Colombia, the nation's second largest city and a nexus for multiple types of trauma exposure. PMID:28265488

  6. Prolonging the expression duration of ultrasound-mediated gene transfection using PEI nanoparticles.

    PubMed

    Lee, Jyun-Lin; Lo, Chia-Wen; Ka, Shuk-Man; Chen, Ann; Chen, Wen-Shiang

    2012-05-30

    Ultrasound (US) irradiation has been found to facilitate the inward transport of genetic materials across cell membranes (sonoporation). However, its transfection efficiency is generally low, and the expression duration of transfected gene is short. Polyethylenimine (PEI), a cationic polymer, has been shown to aggregate plasmid DNA and facilitate its internalization. The purpose of this study is to determine whether PEI can also prolong the expression duration after US-mediated transfection. A mixture of pCMViLUC and 22-kDa linear PEI was transfected to cultured cells or mouse muscle by exposure to 1-MHz pulsed US. The duration of expression was assessed periodically following US treatment. As expected, strong expression of luciferase could be found 30days after the treatment of DNA-PEI complex with US exposure, both in vitro and in vivo. However, without US, only very low transfection level could be obtained in vivo. The DNA/PEI complex showed protective effect against digestion of DNase I enzymes as compared with groups without PEI or to which PEI was added following the mixing of plasmid DNA with DNase I. PEI enhanced the US transfection efficiency by increasing both the intracellular uptake of plasmid DNA and the percentage of transfected cells. Most of the DNA uptake occurred at 3h after US exposure, suggesting that endocytosis took place. Moreover, the PEI-facilitated US gene transfection depended on the ratio of PEI and DNA (N/P ratio), which was different for in-vitro and in-vivo conditions. This system could be applied in future human gene therapies. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Low-background Gamma Spectroscopy at Sanford Underground Laboratory

    NASA Astrophysics Data System (ADS)

    Chiller, Christopher; Alanson, Angela; Mei, Dongming

    2014-03-01

    Rare-event physics experiments require the use of material with unprecedented radio-purity. Low background counting assay capabilities and detectors are critical for determining the sensitivity of the planned ultra-low background experiments. A low-background counting, LBC, facility has been built at the 4850-Level Davis Campus of the Sanford Underground Research Facility to perform screening of material and detector parts. Like many rare event physics experiments, our LBC uses lead shielding to mitigate background radiation. Corrosion of lead brick shielding in subterranean installations creates radon plate-out potential as well as human risks of ingestible or respirable lead compounds. Our LBC facilities employ an exposed lead shield requiring clean smooth surfaces. A cleaning process of low-activity silica sand blasting and borated paraffin hot coating preservation was employed to guard against corrosion due to chemical and biological exposures. The resulting lead shield maintains low background contribution integrity while fully encapsulating the lead surface. We report the performance of the current LBC and a plan to develop a large germanium well detector for PMT screening. Support provided by Sd governors research center-CUBED, NSF PHY-0758120 and Sanford Lab.

  8. Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

    PubMed Central

    2012-01-01

    Background Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. Methods Naïve CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were exposed to one of three types of music--opera (La Traviata), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed. Results CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to

  9. Tissue Distribution And Urinary Excretion Of Inorganic Arsenic And Its Methylated Metabolites In C57BL6 Mice Following Subchronic Exposure To Arsenate In Drinking Water

    EPA Science Inventory

    The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent meta...

  10. Does Use of Low-Molecular-Weight Heparin during Pregnancy Influence the Risk of Prolonged Labor: A Population-Based Cohort Study

    PubMed Central

    Sandström, Anna; Cnattingius, Sven; Wikström, Anna-Karin

    2015-01-01

    Background The use of low-molecular-weight heparins (LMWHs) during pregnancy is increasing. In vitro studies and small clinical studies support the hypothesis that LMWH treatment during pregnancy may reduce duration of labor. The aim of this study was to investigate if use of LMWH is associated with a reduced risk of diagnosis of prolonged labor, after taking maternal, fetal and other delivery characteristics into account. Methods and Findings A population-based cohort study from the Swedish Medical Birth Register from April 2006 through December 2011. We identified 514 875 term (≥37 weeks) deliveries of live singleton infants in cephalic presentation with spontaneous or induced onsets of labor. The Birth Register was linked to the Prescribed Drug Register to retrieve information on dispensed LMWH during pregnancy and to the Patient Register for information on underlying diagnosis for use of LMWH. Diagnosis of prolonged labor in the Birth Register was retrieved from diagnosis at discharge from the delivery hospital. The risk of diagnosis of prolonged labor in relation to treatment with LMWH was assessed using logistic regression analysis to estimate unadjusted and adjusted odds ratios. A total of 5 275 (1.0%) of the pregnant women used LMWH. The absolute risk of diagnosis of prolonged labor for nulliparous women was 19.9% among women using LMWH in third trimester, and 21.2% in women without use of LMWH. For parous women the corresponding absolute risks were 4.3% and 4.7%, respectively. Compared to nulliparous women without use of LMWH, nulliparous women with LMWH during third trimester had an odds ratio (OR) of 0.92 (95% CI 0.81–1.05, p-value: 0.051) for diagnosis of prolonged labor in unadjusted analyses and after adjustments for maternal characteristics, gestational age and epidural analgesia the OR was 1.00 (95% CI 0.87–1.15, p-value: 0.673). Parous women treated with LMWH in third trimester presented the same pattern, unadjusted OR for diagnosis of

  11. TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN C57BL/6 MICE FOLLOWING SUBCHRONIC EXPOSURE TO ARSENATE (ASV) IN DRINKING WATER

    EPA Science Inventory

    The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent metabolites hav...

  12. Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows.

    PubMed

    Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid; Svendsen, Susanne Wulff

    2018-03-01

    We aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate if exposure to hand-arm vibration (HAV) is an independent risk factor. We used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003-2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register-based occupational codes (1993-2007) to a general population job exposure matrix to obtain year-by-year exposure intensities on measurement scales for force, upper arm elevation >90° and repetition and expert rated intensities of exposure to HAV. For 10-year exposure time windows, we calculated the duration of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures. We found indications of safe exposure intensities for repetition (median angular velocity <45°/s), while force exertion ≥10% of maximal voluntary electrical activity and upper arm elevation >90° >2 min/day implied an increased risk reaching ORs of 1.7 and 1.5 after 10 years at low intensities. No associations were found for HAV. We found indications of safe exposure intensities for repetition. Any intensities of force and upper arm elevation >90° above minimal implied an increased risk across 10-year exposure time windows. No independent associations were found for HAV. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Use of population exposure frequency distributions to simulate effects of policy interventions on NO2 exposure

    NASA Astrophysics Data System (ADS)

    Dimitroulopoulou, C.; Ashmore, M. R.; Terry, A. C.

    2017-02-01

    Health effects of air pollution on individuals depend on their personal exposure, but few modelling tools are available which can predict how the distribution of personal exposures within a city will change in response to policies to reduce emissions both indoors and outdoors. We describe a new probabilistic modelling framework (INDAIR-2/EXPAIR), which provides predictions of the personal exposure frequency distribution (PEFD) across a city to assess the effects of both reduced emissions from home sources and reduced roadside concentrations on population exposure. The model uses a national time activity database, which gives the percentage of each population group in different residential and non-residential micro-environments, and links this, for the home, to predictions of concentrations from a three-compartment model, and for non-residential microenvironments to empirical indoor/outdoor ratios. This paper presents modelled PEFDs for NO2 in the city of Leicester, for children, the elderly, and office workers, comparing results in different seasons and on different days of the week. While the mean NO2 population exposure was close to, or below the urban background concentration, the 95%ile of the PEFD was well above the urban background concentration. The relationship between both mean and 95%ile PEFD and urban background concentrations was strongly influenced by air exchange rate. The 24 h mean PEFD showed relative small differences between the population groups, with both removal of home sources and reductions of roadside concentrations on roads with a high traffic density having similar effects in reducing mean exposure. In contrast, the 1 h maximum of the PEFD was significantly higher for children and the elderly than for office workers, and showed a much greater response to reduced home emissions in these groups. The results demonstrate the importance of understanding the dynamics of NO2 exposure at a population level within different groups, if the benefits

  14. Prolonged sitting in cars: prevalence, socio-demographic variations, and trends.

    PubMed

    Sugiyama, Takemi; Merom, Dafna; van der Ploeg, Hidde P; Corpuz, Grace; Bauman, Adrian; Owen, Neville

    2012-10-01

    Prolonged sitting is detrimentally associated with health outcomes. However, the prevalence and characteristics of those who sit in cars for long periods are not well understood. This study examined the population prevalence, socio-demographic variations, and trends for prolonged sitting in cars among adults. Using the Sydney Greater Metropolitan Area Household Travel Survey, the prevalence of prolonged sitting time in cars (≥2 h/day) was calculated for four 3-year periods (1997-99, 2000-02, 2003-05, and 2006-08) for each population subgroup. Trends were calculated as the mean change in prevalence between adjacent survey periods. Cars were used for 66% of the total trips recorded (n=336,505). The prevalence of prolonged sitting time in cars was 16-18% in men, and 10-12% in women. Relatively higher prevalence rates were found among middle-age groups (men: 20-22%, women: 12-15%), full-time workers (men: 21-24%, women: 14-15%), those with higher income (men: 21-25%, women: 14-16%), couples with children (men: 20-21%, women: 12-14%), and those living in outer suburbs (men: 20-23%, women: 12-13%). Trends were stable in men, but increasing in women. Several subgroups (older age; living in regional suburbs) also showed increasing trends. These findings provide evidence to inform integrated approaches to measurement and policy development on prolonged car use among the public health, urban planning, and transport sectors. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. The Effects of Background Information on Standarized Test Scores.

    ERIC Educational Resources Information Center

    Feeley, Joan T.; Wepner, Shelley B.

    A study was conducted to determine the effects of exposure to the topics included on the comprehension subtest of the Nelson-Denny Reading Test (ND), Form F, on college freshmen's performance on the test. In addition, the study investigated whether those students with background information would indicate their awareness of this knowledge on a…

  16. Background and Employability of Mobile vs. Non-Mobile Students

    ERIC Educational Resources Information Center

    Wiers-Jenssen, Jannecke

    2011-01-01

    In this paper, a comparison is made of the background and the early career of graduates with higher education from abroad to graduates with all domestic degrees, based on a survey among Norwegian graduates. Results show that those who have studied abroad constitute a selected group regarding social origin and mobility capital (exposure to…

  17. Prevalence of QT interval prolongation in patients admitted to cardiac care units and frequency of subsequent administration of QT interval-prolonging drugs: a prospective, observational study in a large urban academic medical center in the US.

    PubMed

    Tisdale, James E; Wroblewski, Heather A; Overholser, Brian R; Kingery, Joanna R; Trujillo, Tate N; Kovacs, Richard J

    2012-06-01

    Cardiac arrest due to torsades de pointes (TdP) is a rare but catastrophic event in hospitals. Patients admitted to cardiac units are at higher risk of drug-induced QT interval prolongation and TdP, due to a preponderance of risk factors. Few data exist regarding the prevalence of QT interval prolongation in patients admitted to cardiac units or the frequency of administering QT interval-prolonging drugs to patients presenting with QT interval prolongation. The aim of this study was to determine the prevalence of Bazett's-corrected QT (QT(c)) interval prolongation upon admission to cardiac units and the proportion of patients presenting with QT(c) interval prolongation who are subsequently administered QT interval-prolonging drugs during hospitalization. This was a prospective, observational study conducted over a 1-year period (October 2008-October 2009) in 1159 consecutive patients admitted to two cardiac units in a large urban academic medical centre located in Indianapolis, IN, USA. Patients were enrolled into the study at the time of admission to the hospital and were followed daily during hospitalization. Exclusion criteria were age <18 years, ECG rhythm of complete ventricular pacing, and patient designation as 'outpatient' in a bed and/or duration of stay <24 hours. Data collected included demographic information, past medical history, daily progress notes, medication administration records, laboratory data, ECGs, telemetry monitoring strips and diagnostic reports. All patients underwent continuous cardiac telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of admission. QT intervals were determined manually from lead II of 12-lead ECGs or from continuous lead II telemetry monitoring strips. QT(c) interval prolongation was defined as ≥470 ms for males and ≥480 ms for females. In both males and females, QT(c) interval >500 ms was considered abnormally high. A medication was classified as QT interval-prolonging if there

  18. Domestic Asbestos Exposure: A Review of Epidemiologic and Exposure Data

    PubMed Central

    Goswami, Emily; Craven, Valerie; Dahlstrom, David L.; Alexander, Dominik; Mowat, Fionna

    2013-01-01

    Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities) among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12) of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE) of 5.02 (95% confidence interval [CI]: 2.48–10.13). This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners). The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6), though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2). Several exposure-related studies describe results from airborne samples collected within the home (n = 3), during laundering of contaminated clothing (n = 1) or in controlled exposure simulations (n = 5) of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6) were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers’ exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically. PMID:24185840

  19. Reappraising Abstract Paintings after Exposure to Background Information

    PubMed Central

    Park, Seongmin A.; Yun, Kyongsik; Jeong, Jaeseung

    2015-01-01

    Can knowledge help viewers when they appreciate an artwork? Experts’ judgments of the aesthetic value of a painting often differ from the estimates of naïve viewers, and this phenomenon is especially pronounced in the aesthetic judgment of abstract paintings. We compared the changes in aesthetic judgments of naïve viewers while they were progressively exposed to five pieces of background information. The participants were asked to report their aesthetic judgments of a given painting after each piece of information was presented. We found that commentaries by the artist and a critic significantly increased the subjective aesthetic ratings. Does knowledge enable experts to attend to the visual features in a painting and to link it to the evaluative conventions, thus potentially causing different aesthetic judgments? To investigate whether a specific pattern of attention is essential for the knowledge-based appreciation, we tracked the eye movements of subjects while viewing a painting with a commentary by the artist and with a commentary by a critic. We observed that critics’ commentaries directed the viewers’ attention to the visual components that were highly relevant to the presented commentary. However, attention to specific features of a painting was not necessary for increasing the subjective aesthetic judgment when the artists’ commentary was presented. Our results suggest that at least two different cognitive mechanisms may be involved in knowledge- guided aesthetic judgments while viewers reappraise a painting. PMID:25945789

  20. Prolonged acid rain facilitates soil organic carbon accumulation in a mature forest in Southern China.

    PubMed

    Wu, Jianping; Liang, Guohua; Hui, Dafeng; Deng, Qi; Xiong, Xin; Qiu, Qingyan; Liu, Juxiu; Chu, Guowei; Zhou, Guoyi; Zhang, Deqiang

    2016-02-15

    With the continuing increase in anthropogenic activities, acid rain remains a serious environmental threat, especially in the fast developing areas such as southern China. To detect how prolonged deposition of acid rain would influence soil organic carbon accumulation in mature subtropical forests, we conducted a field experiment with simulated acid rain (SAR) treatments in a monsoon evergreen broadleaf forest at Dinghushan National Nature Reserve in southern China. Four levels of SAR treatments were set by irrigating plants with water of different pH values: CK (the control, local lake water, pH ≈ 4.5), T1 (water pH=4.0), T2 (water pH=3.5), and T3 (water pH=3.0). Results showed reduced pH measurements in the topsoil exposed to simulated acid rains due to soil acidification. Soil respiration, soil microbial biomass and litter decomposition rates were significantly decreased by the SAR treatments. As a result, T3 treatment significantly increased the total organic carbon by 24.5% in the topsoil compared to the control. Furthermore, surface soil became more stable as more recalcitrant organic matter was generated under the SAR treatments. Our results suggest that prolonged acid rain exposure may have the potential to facilitate soil organic carbon accumulation in the subtropical forest in southern China. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Prolonged energy harvesting for ingestible devices.

    PubMed

    Nadeau, Phillip; El-Damak, Dina; Glettig, Dean; Kong, Yong Lin; Mo, Stacy; Cleveland, Cody; Booth, Lucas; Roxhed, Niclas; Langer, Robert; Chandrakasan, Anantha P; Traverso, Giovanni

    2017-01-01

    Ingestible electronics have revolutionized the standard of care for a variety of health conditions. Extending the capacity and safety of these devices, and reducing the costs of powering them, could enable broad deployment of prolonged monitoring systems for patients. Although prior biocompatible power harvesting systems for in vivo use have demonstrated short minute-long bursts of power from the stomach, not much is known about the capacity to power electronics in the longer term and throughout the gastrointestinal tract. Here, we report the design and operation of an energy-harvesting galvanic cell for continuous in vivo temperature sensing and wireless communication. The device delivered an average power of 0.23 μW per mm 2 of electrode area for an average of 6.1 days of temperature measurements in the gastrointestinal tract of pigs. This power-harvesting cell has the capacity to provide power for prolonged periods of time to the next generation of ingestible electronic devices located in the gastrointestinal tract.

  2. Different adaptations of Chinese winter-over expeditioners during prolonged Antarctic and sub-Antarctic residence.

    PubMed

    Chen, Nan; Wu, Quan; Li, Hao; Zhang, Tao; Xu, Chengli

    2016-05-01

    Prolonged residence in Antarctica is characterized by exposure to isolated, confined, and extreme (ICE) environment. Winter-over expeditioners at research stations often exhibit a complex of psychophysiological symptoms, which varied by stations and sociocultural backgrounds. To understand the different patterns of psychophysiological responses provoked by environmental stress, we conducted a longitudinal assessment of mood and endocrine function in two groups of Chinese expeditioners who were deployed to sub-Antarctic (Great Wall Station, 62°S, N = 12) and Antarctic (Zhongshan Station, 66°S, N = 16) from December 2003 to 2005. Measures of mood, thyroid function, the levels of plasma catecholamine, and circulating interleukins were obtained at departure from China, mid-winter (Antarctica), end of winter (Antarctica), and return to China, respectively. The Zhongshan Station crew experienced significant increases in fatigue, anger, tension, confusion, and decrease in free thyroxine (FT4), norepinephrine (NE), and epinephrine (E) during the winter, increase in thyrotropin (TSH) and total triiodothyronine (TT3) when returning, whereas their counterparts at Great Wall Station only experienced increased TT3 after deployment. Moreover, compared with the Great Wall Station crew, the Zhongshan Station crew exhibited greater increase in anger, greater decrease in FT4, total thyroxine (TT4), NE and E over the winter, and greater increase in TSH when returning. Chinese expeditioners who lived and worked at the Antarctic station and the sub-Antarctic station for over a year showed different change patterns in mood and endocrine hormones. Negative mood and endocrine dysfunction were positively associated with the severity of environment. The study is a supplement to scientific knowledge on psychophysiological variation under ICE environment, which has certain applied value for the development of preventive countermeasures or interventions.

  3. Different adaptations of Chinese winter-over expeditioners during prolonged Antarctic and sub-Antarctic residence

    NASA Astrophysics Data System (ADS)

    Chen, Nan; Wu, Quan; Li, Hao; Zhang, Tao; Xu, Chengli

    2016-05-01

    Prolonged residence in Antarctica is characterized by exposure to isolated, confined, and extreme (ICE) environment. Winter-over expeditioners at research stations often exhibit a complex of psychophysiological symptoms, which varied by stations and sociocultural backgrounds. To understand the different patterns of psychophysiological responses provoked by environmental stress, we conducted a longitudinal assessment of mood and endocrine function in two groups of Chinese expeditioners who were deployed to sub-Antarctic (Great Wall Station, 62°S, N = 12) and Antarctic (Zhongshan Station, 66°S, N = 16) from December 2003 to 2005. Measures of mood, thyroid function, the levels of plasma catecholamine, and circulating interleukins were obtained at departure from China, mid-winter (Antarctica), end of winter (Antarctica), and return to China, respectively. The Zhongshan Station crew experienced significant increases in fatigue, anger, tension, confusion, and decrease in free thyroxine (FT4), norepinephrine (NE), and epinephrine (E) during the winter, increase in thyrotropin (TSH) and total triiodothyronine (TT3) when returning, whereas their counterparts at Great Wall Station only experienced increased TT3 after deployment. Moreover, compared with the Great Wall Station crew, the Zhongshan Station crew exhibited greater increase in anger, greater decrease in FT4, total thyroxine (TT4), NE and E over the winter, and greater increase in TSH when returning. Chinese expeditioners who lived and worked at the Antarctic station and the sub-Antarctic station for over a year showed different change patterns in mood and endocrine hormones. Negative mood and endocrine dysfunction were positively associated with the severity of environment. The study is a supplement to scientific knowledge on psychophysiological variation under ICE environment, which has certain applied value for the development of preventive countermeasures or interventions.

  4. Caring for a Child with Learning Disabilities over a Prolonged Period of Time: An Exploratory Survey on the Experiences and Health of Older Parent Carers Living in Scotland

    ERIC Educational Resources Information Center

    Cairns, Deborah; Brown, Jayne; Tolson, Debbie; Darbyshire, Chris

    2014-01-01

    Background: The negative health impacts of prolonged caregiving are widely reported. However, there is a paucity of evidence concerning the impacts of a lifetime of caring on older parents of offspring with learning disabilities. Design and Methods: An exploratory postal survey including the Medical Outcome Study (Short Form) 36 version 2…

  5. Evidence of Health Risks Associated with Prolonged Standing at Work and Intervention Effectiveness

    PubMed Central

    Waters, Thomas R.; Dick, Robert B.

    2015-01-01

    Purpose Prolonged standing at work has been shown to be associated with a number of potentially serious health outcomes, such as lower back and leg pain, cardiovascular problems, fatigue, discomfort, and pregnancy related health outcomes. Recent studies have been conducted examining the relationship between these health outcomes and the amount of time spent standing while on the job. The purpose of this article was to provide a review of the health risks and interventions for workers and employers that are involved in occupations requiring prolonged standing. A brief review of recommendations by governmental and professional organizations for hours of prolonged standing is also included. Findings Based on our review of the literature, there seems to be ample evidence showing that prolonged standing at work leads to adverse health outcomes. Review of the literature also supports the conclusion that certain interventions are effective in reducing the hazards associated with prolonged standing. Suggested interventions include the use of floor mats, sit-stand workstations/chairs, shoes, shoe inserts and hosiery or stockings. Studies could be improved by using more precise definitions of prolonged standing (e.g., duration, movement restrictions, and type of work), better measurement of the health outcomes and more rigorous study protocols. Conclusion and Clinical Relevance Use of interventions and following suggested guidelines on hours of standing from governmental and professional organizations should reduce the health risks from prolonged standing. PMID:25041875

  6. Perioperative Opioid Analgesics and Hip Arthroscopy: Trends, Risk Factors for Prolonged Use, and Complications.

    PubMed

    Anciano Granadillo, Victor; Cancienne, Jourdan M; Gwathmey, F Winston; Werner, Brian C

    2018-05-02

    The purpose of this article is to (1) examine trends in preoperative and prolonged postoperative opioid analgesic use in patient undergoing hip arthroscopy, (2) characterize risk factors for prolonged opioid analgesic use following hip arthroscopy, and (3) explore preoperative and prolonged postoperative opioid analgesic use as independent risk factors for complications following hip arthroscopy. A private insurance database was queried for patients undergoing hip arthroscopy from 2007 to 2015 with a minimum of 6 months of follow-up. Independent risk factors for prolonged opioid analgesic use were determined. Preoperative and prolonged opioid analgesic use as risk factors for complications were examined. There was a significantly decreasing trend in preoperative (P = .002) and prolonged postoperative (P = .009) opioid analgesic use. The most significant risk factor for prolonged postoperative opioid analgesic use was preoperative use (odds ratio [OR], 3.61; P < .0001). Other preoperative prescriptions, including muscle relaxants (OR, 1.5; P < .0001) and anxiolytics (OR, 2.0; P < .0001), were also significant risk factors. Preoperative opioid analgesic use was a significant risk factor for postoperative complications, including emergency room visits (OR, 2.1; P < .0001) and conversion to total hip arthroplasty (THA) (OR, 1.6; P < .0001). Prolonged postoperative opioid analgesic use was associated with a higher risk of revision hip arthroscopy (OR, 1.4; P = .0004) and conversion to THA (OR, 1.8; P < .0001). More than a quarter of patients undergoing hip arthroscopy continue to receive opioid analgesic prescriptions more than 3 months postoperatively. The most significant risk factor for prolonged opioid analgesic use is preoperative opioid analgesic use. Additionally, anxiolytics, substance use or abuse, morbid obesity, and back pain were among the more notable risk factors for prolonged postoperative opioid analgesic use. Preoperative and prolonged

  7. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pavlikova, Nela, E-mail: nela.pavlikova@lf3.cuni.cz; Smetana, Pavel; Halada, Petr

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cellmore » line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha

  8. Clinical Meaning of Early Oxygenation Improvement in Severe Acute Respiratory Distress Syndrome under Prolonged Prone Positioning

    PubMed Central

    Lee, Kwangha; Kim, Mi-Young; Yoo, Jung-Wan; Hong, Sang-Bum; Lim, Chae-Man

    2010-01-01

    Background/Aims Ventilating patients with acute respiratory distress syndrome (ARDS) in the prone position has been shown to improve arterial oxygenation, but prolonged prone positioning frequently requires continuous deep sedation, which may be harmful to patients. We evaluated the meaning of early gas exchange in patients with severe ARDS under prolonged (≥ 12 hours) prone positioning. Methods We retrospectively studied 96 patients (mean age, 60.1 ± 15.6 years; 75% men) with severe ARDS (PaO2/FiO2 ≤ 150 mmHg) admitted to a medical intensive care unit (MICU). The terms "PaO2 response" and "PaCO2 response" represented responses that resulted in increases in the PaO2/FiO2 ratio of ≥ 20 mmHg and decreases in PaCO2 of ≥ 1 mmHg, respectively, 8 to 12 hours after first placement in the prone position. Results The mean duration of prone positioning was 78.5 ± 61.2 hours, and the 28-day mortality rate after MICU admission was 56.3%. No significant difference in clinical characteristics was observed between PaO2 and PaCO2 responders and non-responders. The PaO2 responders after prone positioning showed an improved 28-day outcome, compared with non-responders by Kaplan-Meier survival estimates (p < 0.05 by the log-rank test), but the PaCO2 responders did not. Conclusions Our results suggest that the early oxygenation improvement after prone positioning might be associated with an improved 28-day outcome and may be an indicator to maintain prolonged prone positioning in patients with severe ARDS. PMID:20195404

  9. Flame exposure time on Langmuir probe degradation, ion density, and thermionic emission for flame temperature.

    PubMed

    Doyle, S J; Salvador, P R; Xu, K G

    2017-11-01

    The paper examines the effect of exposure time of Langmuir probes in an atmospheric premixed methane-air flame. The effects of probe size and material composition on current measurements were investigated, with molybdenum and tungsten probe tips ranging in diameter from 0.0508 to 0.1651 mm. Repeated prolonged exposures to the flame, with five runs of 60 s, resulted in gradual probe degradations (-6% to -62% area loss) which affected the measurements. Due to long flame exposures, two ion saturation currents were observed, resulting in significantly different ion densities ranging from 1.16 × 10 16 to 2.71 × 10 19 m -3 . The difference between the saturation currents is caused by thermionic emissions from the probe tip. As thermionic emission is temperature dependent, the flame temperature could thus be estimated from the change in current. The flame temperatures calculated from the difference in saturation currents (1734-1887 K) were compared to those from a conventional thermocouple (1580-1908 K). Temperature measurements obtained from tungsten probes placed in rich flames yielded the highest percent error (9.66%-18.70%) due to smaller emission current densities at lower temperatures. The molybdenum probe yielded an accurate temperature value with only 1.29% error. Molybdenum also demonstrated very low probe degradation in comparison to the tungsten probe tips (area reductions of 6% vs. 58%, respectively). The results also show that very little exposure time (<5 s) is needed to obtain a valid ion density measurement and that prolonged flame exposures can yield the flame temperature but also risks damage to the Langmuir probe tip.

  10. Modeling Particle Exposure in US Trucking Terminals

    PubMed Central

    Davis, ME; Smith, TJ; Laden, F; Hart, JE; Ryan, LM; Garshick, E

    2007-01-01

    Multi-tiered sampling approaches are common in environmental and occupational exposure assessment, where exposures for a given individual are often modeled based on simultaneous measurements taken at multiple indoor and outdoor sites. The monitoring data from such studies is hierarchical by design, imposing a complex covariance structure that must be accounted for in order to obtain unbiased estimates of exposure. Statistical methods such as structural equation modeling (SEM) represent a useful alternative to simple linear regression in these cases, providing simultaneous and unbiased predictions of each level of exposure based on a set of covariates specific to the exposure setting. We test the SEM approach using data from a large exposure assessment of diesel and combustion particles in the US trucking industry. The exposure assessment includes data from 36 different trucking terminals across the United States sampled between 2001 and 2005, measuring PM2.5 and its elemental carbon (EC), organic carbon (OC) components, by personal monitoring, and sampling at two indoor work locations and an outdoor “background” location. Using the SEM method, we predict: 1) personal exposures as a function of work related exposure and smoking status; 2) work related exposure as a function of terminal characteristics, indoor ventilation, job location, and background exposure conditions; and 3) background exposure conditions as a function of weather, nearby source pollution, and other regional differences across terminal sites. The primary advantage of SEMs in this setting is the ability to simultaneously predict exposures at each of the sampling locations, while accounting for the complex covariance structure among the measurements and descriptive variables. The statistically significant results and high R2 values observed from the trucking industry application supports the broader use of this approach in exposure assessment modeling. PMID:16856739

  11. Variation in Definition of Prolonged Mechanical Ventilation.

    PubMed

    Rose, Louise; McGinlay, Michael; Amin, Reshma; Burns, Karen Ea; Connolly, Bronwen; Hart, Nicholas; Jouvet, Philippe; Katz, Sherri; Leasa, David; Mawdsley, Cathy; McAuley, Danny F; Schultz, Marcus J; Blackwood, Bronagh

    2017-10-01

    Consistency of definitional criteria for terminology applied to describe subject cohorts receiving mechanical ventilation within ICU and post-acute care settings is important for understanding prevalence, risk stratification, effectiveness of interventions, and projections for resource allocation. Our objective was to quantify the application and definition of terms for prolonged mechanical ventilation. We conducted a scoping review of studies (all designs except single-case study) reporting a study population (adult and pediatric) using the term prolonged mechanical ventilation or a synonym. We screened 5,331 references, reviewed 539 full-text references, and excluded 120. Of the 419 studies (representing 38 countries) meeting inclusion criteria, 297 (71%) reported data on a heterogeneous subject cohort, and 66 (16%) included surgical subjects only (46 of those 66, 70% cardiac surgery). Other studies described COPD (16, 4%), trauma (22, 5%), neuromuscular (17, 4%), and sepsis (1, 0.2%) cohorts. A total of 741 terms were used to refer to the 419 study cohorts. The most common terms were: prolonged mechanical ventilation (253, 60%), admission to specialized unit (107, 26%), and long-term mechanical ventilation (79, 19%). Some authors (282, 67%) defined their cohorts based on duration of mechanical ventilation, with 154 studies (55%) using this as the sole criterion. We identified 37 different durations of ventilation ranging from 5 h to 1 y, with > 21 d being the most common (28 of 282, 7%). For studies describing a surgical cohort, minimum ventilation duration required for inclusion was ≥ 24 h for 20 of 66 studies (30%). More than half of all studies (237, 57%) did not provide a reason/rationale for definitional criteria used, with only 28 studies (7%) referring to a consensus definition. We conclude that substantial variation exists in the terminology and definitional criteria for cohorts of subjects receiving prolonged mechanical ventilation. Standardization of

  12. PTSD and PTG among Israeli mothers: Opposite facets of exposure to terrorism.

    PubMed

    Shechory Bitton, Mally; Laufer, Avital

    2017-12-01

    The aim of the this study was to test the association between posttraumatic stress disorder (PTSD), posttraumatic growth (PTG), and coping strategies among Israeli mothers with prolonged exposure to rocket missiles. One hundred fifty-two mothers, from the Western Negev region of Israel, took part in the study. Respondents were affected by prolonged exposure to missile attacks even when they themselves had not been hit or injured. A positive correlation was found between PTSD and PTG. Problem-focused coping was found to mediate the relationship between PTSD and PTG; the higher the PTSD, the greater the use of problem-focused coping and the greater the posttraumatic growth. The results help understand the association between PTSD and PTG. The finding whereby problem-focused coping mediates the PTSD-PTG relationship is important for comprehending the association between the variables and the significance of growth in human life and for constructing intervention programs that promote growth following trauma. In addition, the study contributes to raising awareness both of how mothers cope and that they are a separate risk group with distinct growth possibilities. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells.

    PubMed

    Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan

    2015-10-01

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Dynamics Associated with Prolonged Ensiling and Aerobic Deterioration of Total Mixed Ration Silage Containing Whole Crop Corn

    PubMed Central

    Wang, Huili; Ning, Tingting; Hao, Wei; Zheng, Mingli; Xu, Chuncheng

    2016-01-01

    This study investigated the dynamics associated with prolonged ensiling and aerobic deterioration of whole crop corn (WCC) silages and total mixed ration (TMR) silages containing WCC (C-TMR silages) to clarify the differences that account for the enhanced aerobic stability of TMR silages. Laboratory-scale barrel silos were randomly opened after 7, 14, 28, and 56 d of ensiling and were subjected to analyses of fermentation quality, microbial and temperature dynamics during aerobic exposure. WCC and C-TMR silages were both well preserved and microorganisms were inhibited with prolonged ensiling, including lactic acid bacteria. Yeast were inhibited to below the detection limit of 500 cfu/g fresh matter within 28 d of ensiling. Aerobic stability of both silages was enhanced with prolonged ensiling, whereas C-TMR silages were more aerobically stable than WCC silages for the same ensiling period. Besides the high moisture content, the weak aerobic stability of WCC silage is likely attributable to the higher lactic acid content and yeast count, which result from the high water-soluble carbohydrates content in WCC. After silo opening, yeast were the first to propagate and the increase in yeast levels is greater than that of other microorganisms in silages before deterioration. Besides, increased levels of aerobic bacteria were also detected before heating of WCC silages. The temperature dynamics also indicated that yeast are closely associated with the onset of the aerobic deterioration of C-TMR silage, whereas for WCC silages, besides yeast, aerobic bacteria also function in the aerobic deterioration. Therefore, the inclusion of WCC might contribute to the survival of yeast during ensiling but not influence the role of yeast in deterioration of C-TMR silages. PMID:26732329

  15. Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue

    PubMed Central

    Morley, John W.; Tapson, Jonathan; Breen, Paul P.; van Schaik, André

    2016-01-01

    Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45–150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6–8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for <4 hrs. These results indicate that long exposure of calcium AM dyes to the intracellular cytoplasm did not alter the intracellular calcium concentration, the functional range of the dye or viability of the neurons. This data extends our previous work showing that a custom recovery chamber can extend the viability of neuronal tissue, and reliable data for both electrophysiology and imaging can be obtained >24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals. PMID:27183102

  16. Severe bradycardia and prolonged hypotension in ciguatera.

    PubMed

    Chan, Thomas Yan Keung

    2013-06-01

    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  17. Prolonged remission in Caucasian patients with SLE: prevalence and outcomes.

    PubMed

    Zen, Margherita; Iaccarino, Luca; Gatto, Mariele; Bettio, Silvano; Nalotto, Linda; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

    2015-12-01

    To assess the prevalence of prolonged remission in Caucasian patients affected with systemic lupus erythematosus (SLE) and its relationship with damage accrual. Caucasian patients diagnosed with SLE between 1990 and 2009 and quarterly seen from 2009 to 2013 were included in the study. We defined remission as prolonged when lasting ≥5 consecutive years. Three levels of remission were defined using the SLE Disease Activity Index-2000 (SLEDAI-2K): complete remission: no disease activity in corticosteroid-free and immunosuppressant-free patients; clinical remission off corticosteroids: serologically active clinical quiescent (SACQ) disease in corticosteroid-free patients and clinical remission on corticosteroids: SACQ disease in patients taking prednisone 1-5 mg/day. Damage was measured by the SLICC/American College of Rheumatology Damage Index (SDI). 224 patients fulfilled inclusion criteria: 196 (87.5%) were women, mean±SD disease duration 11.2±6.8 years. During the 5-year follow-up, 16 patients (7.1%) achieved prolonged complete remission, 33 (14.7%) prolonged clinical remission off corticosteroids and 35 (15.6%) prolonged clinical remission on corticosteroids. At the multivariate analysis, vasculitis (OR 4.95), glomerulonephritis (OR 2.38) and haematological manifestations (OR 2.19) over the patients' disease course were associated with an unremitted disease. SDI increased more frequently in unremitted (72/140, 51.4%) than in remitted patients (22/84, 26.2%; p=0.001); SDI median increase was higher in unremitted than in remitted patients: 1 (0-3) vs 0 (0-2), respectively (p<0.001). At multivariate analysis, unremitted disease (OR 2.52) and high-dose corticosteroid intake (OR 2.35) were risk factors for damage accrual. Thirty-seven percent of our Caucasian patients achieved a prolonged remission, which was associated with a better outcome in terms of damage accrual. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  18. Work-family conflict and prolonged fatigue among Japanese married male physicians.

    PubMed

    Ohta, Hiroshi; Wada, Koji; Kawashima, Masatoshi; Arimatsu, Mayuri; Higashi, Toshiaki; Yoshikawa, Toru; Aizawa, Yoshiharu

    2011-12-01

    Fatigue experienced by physicians may not only endanger their own health but may also affect the safety of patients. Such fatigue may be associated with the work environment and personal factors such as work-family conflict (WFC). This study aimed to determine the association between WFC and prolonged fatigue among Japanese married male physicians. Physicians who graduated from a Japanese medical school answered a mailed anonymous self-report questionnaire. For assessment of WFC and prolonged fatigue, the Japanese versions of the WFC scale and the Checklist of Individual Strength questionnaire (CIS) were used. Prolonged fatigue was defined as the upper quartile of total CIS scores. The WFC scale comprises six dimensions. Total scores were divided into tertiles: low, intermediate, and high levels of WFC. A multiple logistic regression analysis was performed to examine the association between WFC and prolonged fatigue. A total of 540 male physicians answered the questionnaire, and the data of 444 married male physicians were analyzed. The data were then adjusted for age and work condition factors. Prolonged fatigue was significantly associated with high strain-based work interference with family (WIF; corrected odds ratio, 5.56; 95% confidence interval, 2.55-12.1), intermediate strain-based WIF (2.53, 1.25-5.10), high time-based family interference with work (FIW; 1.92, 1.08-3.40), and there was a weak association with high strain-based FIW (1.93, 0.98-3.83). Employers should take measures to improve working conditions in hospitals, and give physicians the opportunity to learn how to cope with WFC. These measures could ultimately help prevent prolonged fatigue.

  19. Prolonged Mechanical Ventilation as a Predictor of Mortality After Cardiac Surgery.

    PubMed

    Fernandez-Zamora, Maria Dolores; Gordillo-Brenes, Antonio; Banderas-Bravo, Esther; Arboleda-Sánchez, José Andrés; Hinojosa-Pérez, Rafael; Aguilar-Alonso, Eduardo; Herruzo-Aviles, Ángel; Curiel-Balsera, Emilio; Sánchez-Rodríguez, Ángel; Rivera-Fernández, Ricardo

    2018-05-01

    Mortality among the small percentage of cardiac surgery patients receiving prolonged mechanical ventilation is high, but this issue appears to be inadequately addressed in guidelines. This study is a retrospective analysis of prospective, multi-center, and observational study in Spain including all adults undergoing cardiac surgery in 3 Andalusian hospitals between June 2008 and December 2012. The study included 3,588 adults with mean ± SD age of 63.5 ± 12.8 y and with median (interquartile range) EuroSCORE of 5 (3-7) points. Prolonged mechanical ventilation (> 24 h) was required by 415 subjects (11.6%), with ICU mortality of 44.3% (184 subjects), and was not required by 3,173 subjects (88.4%), with ICU mortality of 3.1% (99 subjects, P < .001). Prolonged mechanical ventilation was associated with more complications and was required by 4.5% of subjects with a EuroSCORE <5, 11.2% with a score of 5-7, 27.2% with a score of 8-10, and 32.2% with a score > 10. In the multivariable analysis, ICU mortality was associated with illness severity, duration of bypass surgery, surgery type, and prolonged mechanical ventilation (odds ratio 15.19, 95% CI 11.56-22.09). The main cause of death was multiple organ failure and sepsis in subjects who required prolonged mechanical ventilation (50.3%) and cardiogenic shock in those who did not (59.2%). Prolonged postoperative mechanical ventilation was required by 10-20% of cardiac surgery subjects, who constitute a specific group that represents most of the postoperative mortality, which is associated with multiple organ failure and sepsis. Copyright © 2018 by Daedalus Enterprises.

  20. Vision and Vestibular System Dysfunction Predicts Prolonged Concussion Recovery in Children.

    PubMed

    Master, Christina L; Master, Stephen R; Wiebe, Douglas J; Storey, Eileen P; Lockyer, Julia E; Podolak, Olivia E; Grady, Matthew F

    2018-03-01

    Up to one-third of children with concussion have prolonged symptoms lasting beyond 4 weeks. Vision and vestibular dysfunction is common after concussion. It is unknown whether such dysfunction predicts prolonged recovery. We sought to determine which vision or vestibular problems predict prolonged recovery in children. A retrospective cohort of pediatric patients with concussion. A subspecialty pediatric concussion program. Four hundred thirty-two patient records were abstracted. Presence of vision or vestibular dysfunction upon presentation to the subspecialty concussion program. The main outcome of interest was time to clinical recovery, defined by discharge from clinical follow-up, including resolution of acute symptoms, resumption of normal physical and cognitive activity, and normalization of physical examination findings to functional levels. Study subjects were 5 to 18 years (median = 14). A total of 378 of 432 subjects (88%) presented with vision or vestibular problems. A history of motion sickness was associated with vestibular dysfunction. Younger age, public insurance, and presence of headache were associated with later presentation for subspecialty concussion care. Vision and vestibular problems were associated within distinct clusters. Provocable symptoms with vestibulo-ocular reflex (VOR) and smooth pursuits and abnormal balance and accommodative amplitude (AA) predicted prolonged recovery time. Vision and vestibular problems predict prolonged concussion recovery in children. A history of motion sickness may be an important premorbid factor. Public insurance status may represent problems with disparities in access to concussion care. Vision assessments in concussion must include smooth pursuits, saccades, near point of convergence (NPC), and accommodative amplitude (AA). A comprehensive, multidomain assessment is essential to predict prolonged recovery time and enable active intervention with specific school accommodations and targeted rehabilitation.

  1. Bravemind: Advancing the Virtual Iraq/Afghanistan PTSD Exposure Therapy for MST

    DTIC Science & Technology

    2015-06-01

    threatened death, serious injury or sexual violation. Military Sexual Trauma (MST) has been recognized as a significant risk factor for the...development of PTSD. This has become an issue of grave concern within the military, as reports of sexual violations and assaults have been on the rise over the...far, the system was built and delivered and the RCT has commenced. 15. SUBJECT TERMS PTSD, Virtual Reality, Prolonged Exposure, Military Sexual

  2. Exposure to radionuclides in smoke from vegetation fires.

    PubMed

    Carvalho, Fernando P; Oliveira, João M; Malta, Margarida

    2014-02-15

    Naturally occurring radionuclides of uranium, thorium, radium, lead and polonium were determined in bushes and trees and in the smoke from summer forest fires. Activity concentrations of radionuclides in smoke particles were much enriched when compared to original vegetation. Polonium-210 ((210)Po) in smoke was measured in concentrations much higher than all other radionuclides, reaching 7,255 ± 285 Bq kg(-1), mostly associated with the smaller size smoke particles (<1.0 μm). Depending on smoke particle concentration, (210)Po in surface air near forest fires displayed volume concentrations up to 70 m Bq m(-3), while in smoke-free air (210)Po concentration was about 30 μ Bq m(-3). The estimated absorbed radiation dose to an adult member of the public or a firefighter exposed for 24h to inhalation of smoke near forest fires could exceed 5 μSv per day, i.e, more than 2000 times above the radiation dose from background radioactivity in surface air, and also higher than the radiation dose from (210)Po inhalation in a chronic cigarette smoker. It is concluded that prolonged exposure to smoke allows for enhanced inhalation of radionuclides associated with smoke particles. Due to high radiotoxicity of alpha emitting radionuclides, and in particular of (210)Po, the protection of respiratory tract of fire fighters is strongly recommended. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Symptoms in Response to Controlled Diesel Exhaust More Closely Reflect Exposure Perception Than True Exposure

    PubMed Central

    Carlsten, Chris; Oron, Assaf P.; Curtiss, Heidi; Jarvis, Sara; Daniell, William; Kaufman, Joel D.

    2013-01-01

    Background Diesel exhaust (DE) exposures are very common, yet exposure-related symptoms haven’t been rigorously examined. Objective Describe symptomatic responses to freshly generated and diluted DE and filtered air (FA) in a controlled human exposure setting; assess whether such responses are altered by perception of exposure. Methods 43 subjects participated within three double-blind crossover experiments to order-randomized DE exposure levels (FA and DE calibrated at 100 and/or 200 micrograms/m3 particulate matter of diameter less than 2.5 microns), and completed questionnaires regarding symptoms and dose perception. Results For a given symptom cluster, the majority of those exposed to moderate concentrations of diesel exhaust do not report such symptoms. The most commonly reported symptom cluster was of the nose (29%). Blinding to exposure is generally effective. Perceived exposure, rather than true exposure, is the dominant modifier of symptom reporting. Conclusion Controlled human exposure to moderate-dose diesel exhaust is associated with a range of mild symptoms, though the majority of individuals will not experience any given symptom. Blinding to DE exposure is generally effective. Perceived DE exposure, rather than true DE exposure, is the dominant modifier of symptom reporting. PMID:24358296

  4. Prolonged longevity of hypopituitary dwarf mice.

    PubMed

    Bartke, A; Brown-Borg, H; Mattison, J; Kinney, B; Hauck, S; Wright, C

    2001-01-01

    In two types of mutant dwarf mice, congenital deficiencies in pituitary function are associated with remarkably increased life expectancy. In this review, we will describe the key phenotypic characteristics of these animals, the evidence that they exhibit delayed aging, and the mechanisms that are suspected to account for their prolonged longevity.

  5. Microcystin exposure and biochemical outcomes among dialysis patients

    EPA Science Inventory

    Background and aims Dialysis patients appear to be at special risk for exposure to cyanobacteria toxins; episodes of microcystin (MCYST) exposure via dialysate during 1996 and 2001 have been previously reported. During 2001, as many as 44 dialysis patients were exposed to contam...

  6. Tolerability to prolonged lifting tasks. A validation of the recommended limits.

    PubMed

    Capodaglio, P; Bazzini, G

    1997-01-01

    Prolonged physical exertion is subjectively regulated by the perception of effort. This preliminary study was conducted to validate the use of subjective perceptions of effort in assessing objectively tolerable workloads for prolonged lifting tasks. Ten healthy male subjects tested their maximal lifting capacity (MLC) on a lift dynamometer (LidoLift, Loredan Biomed., West Sacramento, CA) and underwent incremental and 30-minute endurance lifting tests. Cardiorespiratory parameters were monitored with an oxygen uptake analyzer, mechanical parameters were calculated using a computerized dynamometer. Ratings of perceived exertion were given on Borg's 10-point scale. Physiological responses to repetitive lifting were matched with subjective perceptions. A single-variable statistical regression for power functions was performed to obtain the individual "iso-perception" curves as functions of the mechanical work exerted. We found that the "iso-perception" curve corresponding to a "moderate" perception of effort may represent the individual "tolerance threshold" for prolonged lifting tasks, since physiological responses at this level of intensity did not change significantly and the respiratory exchange ratio was less than one. The individually tolerable weight for lifting tasks lasting 30 min has been expressed as a percentage of the isoinertial MLC value and compared with the currently recommended limits for prolonged lifting tasks (Italian legislation D.L. 626/94). On the basis of our preliminary results a "tolerance threshold" of 20% MLC has been proposed for prolonged lifting tasks.

  7. Stress response in rat brain after different durations of noise exposure.

    PubMed

    Samson, James; Sheeladevi, Rathinasamy; Ravindran, Rajan; Senthilvelan, Manohar

    2007-01-01

    The alteration in the levels of plasma corticosterone, brain norepinephrine (NE), and expression of brain heat shock proteins (Hsp70) after different durations of noise exposure (acute, 1 day; sub-acute, 15 days; chronic, 30 days) has been studied to analyze their role in combating time-dependent stress effects of noise. Broadband white noise (100dB) exposure to male Wistar albino rats significantly increased the levels of plasma corticosterone and NE in all three durations of noise exposure. The sustained increase observed in their levels in the chronic group suggests that animals are not getting adapted to noise even after 30 days of exposure. The important role of Hsp70 in combating noise induced stress is evident from the significant increase in its expression after chronic exposure, while there was a reciprocal decrease in the NE and corticosterone when compared with their levels after acute and sub-acute noise exposure. This clearly indicates that the time-dependent stress response to noise exposure is a complex mechanism involving highly interconnected systems such as hypothalamo-pituitary-adrenal (HPA) axis, heat shock proteins and may have serious implications in vital organs, particularly in the brain when there is a prolonged noise exposure.

  8. Diet-consumer nitrogen isotope fractionation for prolonged fasting arthropods.

    PubMed

    Mizota, Chitoshi; Yamanaka, Toshiro

    2011-12-01

    Nitrogen acquisition for cellular metabolism during diapause is a primary concern for herbivorous arthropods. Analyses of naturally occurring stable isotopes of nitrogen help elucidate the mechanism. Relevant articles have cited (58 times up to mid-June 2011) anomalously elevated δ(15)N (per mil deviation of (15)N/(14)N, relative to atmospheric nitrogen=0 ‰) values (diet-consumer nitrogen isotope fractionation; up to 12 ‰) for a prolonged fasting raspberry beetle (Byturus tomentosus Degeer (Coleoptera: Byturidae)), which feeds on red raspberries (Rubus idaeus: δ(15)N= ~ +2 ‰). Biologists have hypothesised that extensive recycling of amino acid nitrogen is responsible for the prolonged fasting. Since this hypothesis was proposed in 1995, scientists have integrated biochemical and molecular knowledge to support the mechanism of prolonged diapausing of animals. To test the validity of the recycling hypothesis, we analysed tissue nitrogen isotope ratios for four Japanese arthropods: the shield bug Parastrachia japonensis Scott (Hemiptera: Cydnidae), the burrower bug Canthophorus niveimarginatus Scott (Hemiptera: Cydnidae), leaf beetle Gastrophysa atrocyanea Motschulsky (Coleoptera: Chrysomelidae) and the Japanese oak silkworm Antheraea yamamai (Lepidoptera: Saturniidae), all of which fast for more than 6 months as part of their life-history strategy. Resulting diet-consumer nitrogen isotope discrimination during fasting ranged from 0 to 7‰, as in many commonly known terrestrial arthropods. We conclude that prolonged fasting of arthropods does not always result in anomalous diet-consumer nitrogen isotope fractionation, since the recycling process is closed or nearly closed with respect to nitrogen isotopes.

  9. Identifying Molecular Targets for PTSD Treatment Using Single Prolonged Stress

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0377 TITLE: Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0377 Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress 5b. GRANT...brain GR and β-AR expression alters glutamatergic and GABAergic function in neural circuits that mediate SPS-induced deficits in extinction retention

  10. Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

    PubMed

    Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

    2017-01-01

    A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m 2 ) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Review of exposure therapy: a gold standard for PTSD treatment.

    PubMed

    Rauch, Sheila A M; Eftekhari, Afsoon; Ruzek, Josef I

    2012-01-01

    Prolonged exposure (PE) is an effective first-line treatment for posttraumatic stress disorder (PTSD), regardless of the type of trauma, for Veterans and military personnel. Extensive research and clinical practice guidelines from various organizations support this conclusion. PE is effective in reducing PTSD symptoms and has also demonstrated efficacy in reducing comorbid issues such as anger, guilt, negative health perceptions, and depression. PE has demonstrated efficacy in diagnostically complex populations and survivors of single- and multiple-incident traumas. The PE protocol includes four main therapeutic components (i.e., psychoeducation, in vivo exposure, imaginal exposure, and emotional processing). In light of PE's efficacy, the Veterans Health Administration designed and supported a PE training program for mental health professionals that has trained over 1,300 providers. Research examining the mechanisms involved in PE and working to improve its acceptability, efficacy, and efficiency is underway with promising results.

  12. Grading of Emphysema Is Indispensable for Predicting Prolonged Air Leak After Lung Lobectomy.

    PubMed

    Murakami, Junichi; Ueda, Kazuhiro; Tanaka, Toshiki; Kobayashi, Taiga; Hamano, Kimikazu

    2018-04-01

    The aim of this study was to assess the utility of quantitative computed tomography-based grading of emphysema for predicting prolonged air leak after thoracoscopic lobectomy. A consecutive series of 284 patients undergoing thoracoscopic lobectomy for lung cancer was retrospectively reviewed. Prolonged air leak was defined as air leaks lasting 7 days or longer. The grade of emphysema (emphysema index) was defined by the proportion of the emphysematous lung volume (less than -910 HU) to the total lung volume (-600 to -1,024 HU) by a computer-assisted histogram analysis of whole-lung computed tomography scans. The mean length of chest tube drainage was 1.5 days. Fifteen patients (5.3%) presented with prolonged air leak. According to a receiver-operating characteristics curve analysis, the emphysema index was the best predictor of prolonged air leak, with an area under the curve of 0.85 (95% confidence interval: 0.73 to 0.98). An emphysema index of 35% or greater was the best cutoff value for predicting prolonged air leak, with a negative predictive value of 0.99. The emphysema index was the only significant predictor for the length of postoperative chest tube drainage among conventional variables, including the pulmonary function and resected lobe, in both univariate and multivariate analyses. Prolonged air leak resulted in an increased duration of hospitalization (p < 0.001) and was frequently accompanied by pneumonia or empyema (p < 0.001). The grade of emphysema on computed tomography scan is the best predictor of prolonged air leak that adversely influences early postoperative outcomes. We must take new measures against prolonged air leak in quantitative computed tomography-based high-risk patients. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  13. A STUDY OF THE MASS BALANCE OF DIOXINS AND FURANS IN LACTATING COWS IN BACKGROUND CONDITIONS

    EPA Science Inventory

    Consumption of animal fats account for as much as 95% of the human background exposure to compounds with dioxin-like activity. Although it is generally believed that most domestic meat and dairy animals receive most of their exposure from their feed, there is limited data availa...

  14. An atmospheric exposure chamber for small animals

    NASA Technical Reports Server (NTRS)

    Glaser, R. M.; Weiss, H. S.; Pitt, J. F.; Grimard, M.

    1982-01-01

    The purpose of this project was to design a long-term environmental exposure chamber for small animals. This chamber is capable of producing hypoxic, normoxic and hyperoxic atmospheres which are closely regulated. The chamber, which is of the recycling type, is fashioned after clear plastic germ-free isolators. Oxygen concentration is set and controlled by a paramagnetic O2 analyzer and a 3-way solenoid valve. In this way either O2 or N2 may be provided to the system by way of negative O2 feedback. Relative humidity is maintained at 40-50 percent by a refrigeration type dryer. Carbon dioxide is absorbed by indicating soda lime. A diaphragm pump continuously circulates chamber gas at a high enough flow rate to prevent buildup of CO2 and humidity. This chamber has been used for numerous studies which involve prolonged exposure of small animals to various O2 concentrations.

  15. Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus.

    PubMed

    Behl, Tapan; Kotwani, Anita; Kaur, Ishneet; Goel, Heena

    2015-05-15

    Nephrogenic diabetes insipidus is a clinical sub-type of a diversely expounded disorder, named diabetes insipidus. It is characterized by inability of the renal cells to sense and respond to the stimulus of vasopressin. Amongst its various etiologies, one of the most inevitable causes includes lithium-induced instigation. Numerous studies reported marked histological damage to the kidneys upon long-term treatment with lithium. The recent researches have hypothesized many lithium-mediated mechanisms to explain the damage and dysfunction caused in the kidneys following lithium exposure. These mechanisms, widely, intend to justify the lithium-induced electrolyte imbalance, its interference with some vital proteins and a specific steroidal hormone, obstruction caused to a certain imperative transducer pathway and the renal tubular acidification defect produced on its prolonged therapy. Thorough study of such mechanisms aids in better understanding of the role of lithium in the pathophysiology of this disorder. Hence, the ameliorated knowledge regarding disease-pathology might prove beneficial in developing therapies that aim on disrupting the various lithium-mediated pathways. Hence, this may effectively lead to the demonstration of a novel treatment for nephrogenic diabetes insipidus, which is, at present, limited to the use of diuretics which block lithium reuptake into the body. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. RECOVERY OF VASCULAR FUNCTION AFTER EXPOSURE TO A SINGLE BOUT OF SEGMENTAL VIBRATION

    PubMed Central

    Krajnak, Kristine; Waugh, Stacey; Miller, G. Roger; Johnson, Claud

    2015-01-01

    Work rotation schedules may be used to reduce the negative effects of vibration on vascular function. This study determined how long it takes vascular function to recover after a single exposure to vibration in rats (125 Hz, acceleration 5g). The responsiveness of rat-tail arteries to the vasoconstricting factor UK14304, an α2C-adrenoreceptor agonist, and the vasodilating factor acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a single bout of vibration. Vasoconstriction induced by UK14304 returned to control levels after 1 d of recovery. However, re-dilation induced by ACh did not return to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged effects on peripheral vascular function, and altered vascular responses to a subsequent exposure. To optimize the positive results of work rotation schedules, it is suggested that studies assessing recovery of vascular function after exposure to a single bout of vibration be performed in humans. PMID:25072825

  17. Intrinsic motivation and amotivation in first episode and prolonged psychosis.

    PubMed

    Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L

    2015-12-01

    The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Synchrotron macro ATR-FTIR microspectroscopic analysis of silica nanoparticle-embedded polyester coated steel surfaces subjected to prolonged UV and humidity exposure

    PubMed Central

    Vongsvivut, Jitraporn; Truong, Vi Khanh; Al Kobaisi, Mohammad; Maclaughlin, Shane; Tobin, Mark J.; Crawford, Russell J.

    2017-01-01

    Surface modification of polymers and paints is a popular and effective way to enhance the properties of these materials. This can be achieved by introducing a thin coating that preserves the bulk properties of the material, while protecting it from environmental exposure. Suitable materials for such coating technologies are inorganic oxides, such as alumina, titania and silica; however, the fate of these materials during long-term environmental exposure is an open question. In this study, polymer coatings that had been enhanced with the addition of silica nanoparticles (SiO2NPs) and subsequently subjected to environmental exposure, were characterized both before and after the exposure to determine any structural changes resulting from the exposure. High-resolution synchrotron macro ATR-FTIR microspectroscopy and surface topographic techniques, including optical profilometry and atomic force microscopy (AFM), were used to determine the long-term effect of the environment on these dual protection layers after 3 years of exposure to tropical and sub-tropical climates in Singapore and Queensland (Australia). Principal component analysis (PCA) based on the synchrotron macro ATR-FTIR spectral data revealed that, for the 9% (w/w) SiO2NP/polymer coating, a clear discrimination was observed between the control group (no environmental exposure) and those samples subjected to three years of environmental exposure in both Singapore and Queensland. The PCA loading plots indicated that, over the three year exposure period, a major change occurred in the triazine ring vibration in the melamine resins. This can be attributed to the triazine ring being very sensitive to hydrolysis under the high humidity conditions in tropical/sub-tropical environments. This work provides the first direct molecular evidence, acquired using a high-resolution mapping technique, of the climate-induced chemical evolution of a polyester coating. The observed changes in the surface topography of the

  19. Synchrotron macro ATR-FTIR microspectroscopic analysis of silica nanoparticle-embedded polyester coated steel surfaces subjected to prolonged UV and humidity exposure.

    PubMed

    Vongsvivut, Jitraporn; Truong, Vi Khanh; Al Kobaisi, Mohammad; Maclaughlin, Shane; Tobin, Mark J; Crawford, Russell J; Ivanova, Elena P

    2017-01-01

    Surface modification of polymers and paints is a popular and effective way to enhance the properties of these materials. This can be achieved by introducing a thin coating that preserves the bulk properties of the material, while protecting it from environmental exposure. Suitable materials for such coating technologies are inorganic oxides, such as alumina, titania and silica; however, the fate of these materials during long-term environmental exposure is an open question. In this study, polymer coatings that had been enhanced with the addition of silica nanoparticles (SiO2NPs) and subsequently subjected to environmental exposure, were characterized both before and after the exposure to determine any structural changes resulting from the exposure. High-resolution synchrotron macro ATR-FTIR microspectroscopy and surface topographic techniques, including optical profilometry and atomic force microscopy (AFM), were used to determine the long-term effect of the environment on these dual protection layers after 3 years of exposure to tropical and sub-tropical climates in Singapore and Queensland (Australia). Principal component analysis (PCA) based on the synchrotron macro ATR-FTIR spectral data revealed that, for the 9% (w/w) SiO2NP/polymer coating, a clear discrimination was observed between the control group (no environmental exposure) and those samples subjected to three years of environmental exposure in both Singapore and Queensland. The PCA loading plots indicated that, over the three year exposure period, a major change occurred in the triazine ring vibration in the melamine resins. This can be attributed to the triazine ring being very sensitive to hydrolysis under the high humidity conditions in tropical/sub-tropical environments. This work provides the first direct molecular evidence, acquired using a high-resolution mapping technique, of the climate-induced chemical evolution of a polyester coating. The observed changes in the surface topography of the

  20. The analysis of QT interval and repolarization morphology of the heart in chronic exposure to lead.

    PubMed

    Kiełtucki, J; Dobrakowski, M; Pawlas, N; Średniawa, B; Boroń, M; Kasperczyk, S

    2017-10-01

    There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbB mean ) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbB mean = 20.0-35.0 µg/dl) and high exposure (HE, PbB mean = 35.1-46.4 µg/dl). The control group consisted of 69 healthy workers without occupational exposure to lead. ECG evaluation included the analysis of heart rate (HR), QT interval and repolarization abnormalities. Mean QT interval was significantly greater in the exposed population than in the control group by 2%. In the HE group, mean QT interval was significantly greater than in the control group by 4% and significantly different from those noted in the LE group. Positive correlations between QT interval and lead exposure indices were also reported. Besides, there was a negative correlation between HR and blood lead level. Increased concentration of lead in the blood above 35 μg/dl is associated with the QT interval prolongation, which may trigger arrhythmias when combined with other abnormalities, such as long QT syndrome. Therefore, electrocardiographic evaluation should be a part of a routine monitoring of occupationally exposed populations.

  1. Landscape analysis of pesticide use patterns and ecological exposure

    EPA Science Inventory

    Background/Question/Methods The pesticide exposure landscape in the US is spatially and temporally complex. Researchers studying ecological exposure and effects of pesticides must consider a number of dimensions when framing experiments and conducting assessments. These dimension...

  2. Effect of prolonged hypokinesia on resistance of resistive vessels in rats

    NASA Technical Reports Server (NTRS)

    Saltykova, V. A.

    1982-01-01

    Under the effect of prolonged hypokinesia, the perfusion pressure in resistive vessels, measured under conditions of deep anesthesia and complete denervation, increased by approximately the same degree as arterial pressure in non-anesthetized animals. The increase in arterial, perfusion pressure and the resistance of resistive vessels in animals subjected to prolonged hypokinesia was accompanied by an increase in adrenoreactivity. During prolonged hypokinesia, partial obliteration of the vascular bed of the skeletal muscles plays a significant role in the observed increase in resistance of vessels of the extremities. The increase in adrenoreactivity of the vessels during hypokinesia may be realized as a partial case of an increase in the adrenoreactivity of structures whose innervation is disturbed.

  3. A radon daughter deposition model for low background experiments

    NASA Astrophysics Data System (ADS)

    Rielage, K.; Guiseppe, V. E.; Mastbaum, A.; Elliott, S. R.; Hime, A.

    2009-05-01

    The next generation low-background detectors operating underground, such as dark matter searches and neutrinoless double-beta decay, aim for unprecedented low levels of radioactive backgrounds. Although the radioactive decays of airborne radon (particularly ^222Rn) and its subsequent daughters present in an experiment are potential backgrounds, more troublesome is the deposition of radon daughters on detector materials. Exposure to radon at any stage of assembly of an experiment can result in surface contamination by daughters supported by the long half life (22 y) of ^210Pb on sensitive locations of a detector. An understanding of the potential surface contamination will enable requirements of radon-reduced air and clean room environments for the assembly of low background experiments. It is known that there are a number of environmental factors that govern the deposition of daughters onto surfaces. However, existing models have not explored the impact of some environmental factors important for low background experiments. A test stand has been constructed to deposit radon daughters on various surfaces under a controlled environment in order to develop a deposition model. Results from this test stand and the resulting deposition model will be presented.

  4. Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys

    PubMed Central

    Konopaske, Glenn T.; Dorph-Petersen, Karl-Anton; Sweet, Robert A.; Pierri, Joseph N.; Zhang, Wei; Sampson, Allan R.; Lewis, David A.

    2008-01-01

    Background Both in vivo and post-mortem studies suggest that oligodendrocyte and myelination alterations are present in individuals with schizophrenia. However, it is unclear whether prolonged treatment with antipsychotic medications contributes to these disturbances. We recently reported that chronic exposure of macaque monkeys to haloperidol or olanzapine was associated with a 10−18% lower glial cell number in the parietal grey matter. Consequently, in this study we sought to determine whether the lower glial cell number was due to fewer oligodendrocytes as opposed to lower numbers of astrocytes. Methods Using fluorescent immunocytochemical techniques, we optimized the visualization of each cell type throughout the entire thickness of tissue sections, while minimizing final tissue shrinkage. As a result, we were able to obtain robust stereological estimates of total oligodendrocyte and astrocyte numbers in the parietal grey matter using the optical fractionator method. Results We found a significant 20.5% lower astrocyte number with a non-significant 12.9% lower oligodendrocyte number in the antipsychotic-exposed monkeys. Similar effects were seen in both the haloperidol and olanzapine groups. Conclusion These findings suggest that studies investigating glial cell alterations in schizophrenia must take into account the effect of antipsychotic treatment. PMID:17945195

  5. Analysis of Relationship between Levofloxacin and Corrected QT Prolongation Using a Clinical Data Warehouse

    PubMed Central

    Park, Man Young; Kim, Eun Yeob; Lee, Young Ho; Kim, Woojae; Kim, Ku Sang; Sheen, Seung Soo; Lim, Hong Seok

    2011-01-01

    Objective The aim of this study was to examine whether or not levofloxacin has any relationship with QT prolongation in a real clinical setting by analyzing a clinical data warehouse of data collected from different hospital information systems. Methods Electronic prescription data and medical charts from 3 different hospitals spanning the past 9 years were reviewed, and a clinical data warehouse was constructed. Patients who were both administrated levofloxacin and given electrocardiograms (ECG) were selected. The correlations between various patient characteristics, concomitant drugs, corrected QT (QTc) prolongation, and the interval difference in QTc before and after levofloxacin administration were analyzed. Results A total of 2,176 patients from 3 different hospitals were included in the study. QTc prolongation was found in 364 patients (16.7%). The study revealed that age (OR 1.026, p < 0.001), gender (OR 0.676, p = 0.007), body temperature (OR 1.267, p = 0.024), and cigarette smoking (OR 1.641, p = 0.022) were related with QTc prolongation. After adjusting for related factors, 12 drugs concomitant with levofloxacin were associated with QTc prolongation. For patients who took ECGs before and after administration of levofloxacin during their hospitalization (n = 112), there was no significant difference in QTc prolongation. Conclusions The age, gender, body temperature, cigarette smoking and various concomitant drugs might be related with QTc prolongation. However, there was no definite causal relationship or interaction between levofloxacin and QTc prolongation. Alternative surveillance methods utilizing the massive accumulation of electronic medical data seem to be essential to adverse drug reaction surveillance in future. PMID:21818458

  6. Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig.

    PubMed

    Sun, Hong-Li; Chu, Wen-Feng; Dong, De-Li; Liu, Yan; Bai, Yun-Long; Wang, Xiao-Hui; Zhou, Jin; Yang, Bao-Feng

    2006-04-01

    Arsenic trioxide (As(2)O(3)) has been found to be effective for relapsed or refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim of the present study was to elucidate the ionic mechanisms of As(2)O(3)-induced abnormalities of cardiac electrophysiology and the therapeutic action of choline on As(2)O(3)-caused QT prolongation in guinea pig. Intravenous administration of As(2)O(3) prolonged the QT interval in a dose- and time-dependent manner in guinea pig hearts, and the QT prolongation could be modulated by choline. By using whole-cell patch clamp technique and confocal laser scanning microscopy, we found that As(2)O(3) significantly lengthened action potential duration measured at 50 and 90% of repolarization, enhanced L-type calcium currents (I(Ca-L)), inhibited delayed rectifier potassium currents (I(K)), and increased intracellular calcium concentration ([Ca(2+)](i)) in guinea pig ventricular myocytes. Choline corrected As(2)O(3)-mediated alterations of action potential duration, I(Ca-L) and [Ca(2+)](i), but had no effect on the I(K) inhibition. As(2)O(3) markedly disturbed the normal equilibrium of transmembrane currents (increasing I(Ca-L) and suppressing I(K)) in guinea pig cardiomyocyte, and induced prolongation of action potential duration, further degenerated into QT prolongation. Choline normalized QT interval abnormality and corrected lengthened action potential duration by inhibiting the elevated I(Ca-L) and [Ca(2+)](i) in ventricular myocytes during As(2)O(3) application.

  7. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    PubMed

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. © The Author(s) 2013.

  8. [Validation of prolonged grief disorder instrument for Portuguese population].

    PubMed

    Delalibera, Mayra; Coelho, Alexandra; Barbosa, António

    2011-01-01

    This study aims to validate the Portuguese population the instrument PG-13 (Prolonged Grief Disorder), created by Prigerson et al. (2007) for diagnosis of prolonged grief, whose criteria are: the experience of loss generating intense longing and yearning for the deceased that extends for a period exceeding six months; emotional, cognitive and behavioral symptoms, dysfunction and meaningful life social and occupational functioning. The population includes 102 caregivers of patients accompanied by Support Team Palliative Care, Hospital Santa Maria. The participants are mostly female (82.4%) with mean age of 58.87 (SD: 13.41) and range between 15 and 84 years. Most respondents are widowed (62.1%), and 93.2% of these people are mourning the loss of a spouse. The second largest group of subjects corresponds to married persons (29.5%) who lost one of the parental figures (64.3%) and brothers (14.3%). Deceased family members have an average age of 68.68 (SD: 11.50), with amplitude between 27 and 89 years. The gender distribution in the group of deceased patients are 57.8% male and 42.2 % female. The internal consistency in the instrument is considered very good (a=.932). We found that 22.5% of the population manifests symptoms of prolonged grief. There were no significant differences in terms of socio-demographic variables or in the circumstances of illness and death. Prolonged Grief Disorder is more prevalent in female subjects (91.3%), widowed (68.2%) and in cases where the deceased was being the spouse (65.2%).

  9. INHALATION TOXICOLOGY METHODS: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

    PubMed Central

    Chen, Lung-Chi; Lippmann, Morton

    2015-01-01

    In this review, we outline the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study. We then discuss methods for: 1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; 2) their delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; 3) options for on-line functional assays during and between exposures; and 4) options for serial non-invasive assays of response. In doing so, we go beyond exposures to single agents and simple mixtures, and include methods for evaluating biological responses to complex environmental mixtures. We also emphasize that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology. PMID:25645246

  10. [Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia].

    PubMed

    Braslavsky, D; Keselman, A; Chiesa, A; Bergadá, I

    2012-03-01

    The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  11. Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs.

    PubMed

    Löscher, Wolfgang; Schmidt, Dieter

    2006-08-01

    Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most first-generation AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of

  12. Cellular responses to nicotinic receptor activation are decreased after prolonged exposure to galantamine in human neuroblastoma cells.

    PubMed

    Barik, Jacques; Dajas-Bailador, Federico; Wonnacott, Susan

    2005-08-01

    In this study, we have examined cellular responses of neuroblastoma SH-SY5Y cells after chronic treatment with galantamine, a drug used to treat Alzheimer's disease that has a dual mechanism of action: inhibition of acetylcholinesterase and allosteric potentiation of nicotinic acetylcholine receptors (nAChR). Acute experiments confirmed that maximum potentiation of nicotinic responses occurs at 1 microM galantamine; hence this concentration was chosen for chronic treatment. Exposure to 1 microM galantamine for 4 days decreased Ca(2+) responses (by 19.8+/-3.6%) or [(3)H]noradrenaline ([(3)H]NA) release (by 23.9+/-3.3%) elicited by acute application of nicotine. KCl-evoked increases in intracellular Ca(2+) were also inhibited by 10.0+/-1.9% after 4 days' treatment with galantamine. These diminished responses are consistent with the downregulation of downstream cellular processes. Ca(2+) responses evoked by activation of muscarinic acetylcholine receptors were unaffected by chronic galantamine treatment. Exposure to the more potent acetylcholinesterase inhibitor rivastigmine (1 microM) for 4 days failed to alter nicotine-, KCl-, or muscarinic receptor-evoked increases in intracellular Ca(2+). These observations support the hypothesis that chronic galantamine exerts its effects through interaction with nAChR in this cell line. Exposure to 10 microM nicotine for 4 days produced decreases in acute nicotine- (18.0+/-3.5%) and KCl-evoked Ca(2+) responses (10.6+/-2.5%) and nicotine-evoked [(3)H]NA release (26.0+/-3.3%) that are comparable to the effects of a corresponding exposure to galantamine. Treatment with 1 microM galantamine did not alter numbers of [(3)H]epibatidine-binding sites in SH-SY5Y cells, in contrast to 62% upregulation of these sites in response to 10 microM nicotine. Thus, chronic galantamine acts at nAChR to decrease subsequent functional responses to acute stimulation with nicotine or KCl. This effect appears to be independent of the upregulation of n

  13. Single-dose new insulin glargine 300 U/ml provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes.

    PubMed

    Shiramoto, M; Eto, T; Irie, S; Fukuzaki, A; Teichert, L; Tillner, J; Takahashi, Y; Koyama, M; Dahmen, R; Heise, T; Becker, R H A

    2015-03-01

    Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of new insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) in people with type 1 diabetes mellitus. In two double-blind, randomized, crossover studies, 18 Japanese participants (aged 20-65 years) and 24 European participants (aged 18-65 years) with glycated haemoglobin levels ≤9.0% (≤75 mmol/mol) received single subcutaneous doses of Gla-300, 0.4, 0.6 and 0.9 U/kg (0.9 U/kg in the European study only), and Gla-100, 0.4 U/kg. A 36-h euglycaemic clamp procedure was performed after each dosing. The serum insulin glargine concentration (INS) and glucose infusion rate (GIR) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100. In support of this, the times to 50% of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period, indicating a more evenly distributed exposure and metabolic effect beyond 24 h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6 U/ml Gla-300 doses in both studies compared with the 0.4 U/ml Gla-100 dose. Glucose-lowering activity was detected for up to 36 h with all doses of Gla-300. Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100, maintaining blood glucose control for up to 36 h in euglycaemic clamp settings in Japanese and European participants with type 1 diabetes. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  14. [Health effects of occupational endotoxin exposure: a review and relevance to veterinary practice].

    PubMed

    Smit, Lidwien A M; Wouters, Inge M; Heederik, Dick; Douwes, Jeroen

    2009-10-15

    Endotoxins are cell-wall components of Gram-negative bacteria that are commonly present in plants and plant products and in faecal matter. This review presents an overview of endotoxin exposure levels, associated health effects, and relevance regarding veterinary practice. Exposure to airborne endotoxin is especially high in the agricultural sector and among veterinarians, and in particular among those working with horses or farm animals. Inhalation of endotoxins may cause acute airway inflammation and respiratory symptoms that can lead to (non-allergic) asthma and chronic obstructive pulmonary disease in individuals with prolonged exposure to high levels of endotoxins. Interestingly, recent studies have shown that individuals exposed to high levels of endotoxin also have a lower risk of allergic conditions such as hay fever. Although endotoxin may protect against allergies, it is essential to reduce exposure levels in the agricultural sector in order to prevent workers from developing chronic non-allergic respiratory disorders.

  15. The effects of neonatal isoflurane exposure in mice on brain cell viability, adult behavior, learning, and memory.

    PubMed

    Loepke, Andreas W; Istaphanous, George K; McAuliffe, John J; Miles, Lili; Hughes, Elizabeth A; McCann, John C; Harlow, Kathryn E; Kurth, C Dean; Williams, Michael T; Vorhees, Charles V; Danzer, Steve C

    2009-01-01

    Volatile anesthetics, such as isoflurane, are widely used in infants and neonates. Neurodegeneration and neurocognitive impairment after exposure to isoflurane, midazolam, and nitrous oxide in neonatal rats have raised concerns regarding the safety of pediatric anesthesia. In neonatal mice, prolonged isoflurane exposure triggers hypoglycemia, which could be responsible for the neurocognitive impairment. We examined the effects of neonatal isoflurane exposure and blood glucose on brain cell viability, spontaneous locomotor activity, as well as spatial learning and memory in mice. Seven-day-old mice were randomly assigned to 6 h of 1.5% isoflurane with or without injections of dextrose or normal saline, or to 6 h of room air without injections (no anesthesia). Arterial blood gases and glucose were measured. After 2 h, 18 h, or 11 wk postexposure, cellular viability was assessed in brain sections stained with Fluoro-Jade B, caspase 3, or NeuN. Nine weeks postexposure, spontaneous locomotor activity was assessed, and spatial learning and memory were evaluated in the Morris water maze using hidden and reduced platform trials. Apoptotic cellular degeneration increased in several brain regions early after isoflurane exposure, compared with no anesthesia. Despite neonatal cell loss, however, adult neuronal density was unaltered in two brain regions significantly affected by the neonatal degeneration. In adulthood, spontaneous locomotor activity and spatial learning and memory performance were similar in all groups, regardless of neonatal isoflurane exposure. Neonatal isoflurane exposure led to an 18% mortality, and transiently increased Paco(2), lactate, and base deficit, and decreased blood glucose levels. However, hypoglycemia did not seem responsible for the neurodegeneration, as dextrose supplementation failed to prevent neuronal loss. Prolonged isoflurane exposure in neonatal mice led to increased immediate brain cell degeneration, however, no significant reductions

  16. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    PubMed

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  17. Health inequalities among workers with a foreign background in Sweden: do working conditions matter?

    PubMed

    Dunlavy, Andrea C; Rostila, Mikael

    2013-07-10

    Employment and working conditions are key social determinants of health, yet current information is lacking regarding relationships between foreign background status, working conditions and health among workers in Sweden. This study utilized cross-sectional data from the 2010 Swedish Level of Living Survey (LNU) and the Level of Living Survey for Foreign Born Persons and their Children (LNU-UFB) to assess whether or not health inequalities exist between native Swedish and foreign background workers and if exposure to adverse psychosocial and physical working conditions contributes to the risk for poor health among foreign background workers. A sub-sample of 4,021 employed individuals aged 18-65 was analyzed using logistic regression. Eastern European, Latin American and Other Non-Western workers had an increased risk of both poor self-rated health and mental distress compared to native Swedish workers. Exposure to adverse working conditions only minimally influenced the risk of poor health. Further research should examine workers who are less integrated or who have less secure labor market attachments and also investigate how additional working conditions may influence associations between health and foreign background status.

  18. Health Inequalities among Workers with a Foreign Background in Sweden: Do Working Conditions Matter?

    PubMed Central

    Dunlavy, Andrea C.; Rostila, Mikael

    2013-01-01

    Employment and working conditions are key social determinants of health, yet current information is lacking regarding relationships between foreign background status, working conditions and health among workers in Sweden. This study utilized cross-sectional data from the 2010 Swedish Level of Living Survey (LNU) and the Level of Living Survey for Foreign Born Persons and their Children (LNU-UFB) to assess whether or not health inequalities exist between native Swedish and foreign background workers and if exposure to adverse psychosocial and physical working conditions contributes to the risk for poor health among foreign background workers. A sub-sample of 4,021 employed individuals aged 18–65 was analyzed using logistic regression. Eastern European, Latin American and Other Non-Western workers had an increased risk of both poor self-rated health and mental distress compared to native Swedish workers. Exposure to adverse working conditions only minimally influenced the risk of poor health. Further research should examine workers who are less integrated or who have less secure labor market attachments and also investigate how additional working conditions may influence associations between health and foreign background status. PMID:23846669

  19. High frequency of pertussis in older children and adolescents with prolonged cough in Turkey.

    PubMed

    Aslan, Aslı; Kurugöl, Zafer; Aydemir, Şöhret; Gürsel, Derya; Koturoğlu, Güldane

    2016-01-01

    This study aimed to determine the frequency of B. pertussis infection among Turkish children with prolonged cough. Nasopharyngeal specimens were collected from 7-18 year old children, presenting with prolonged cough of two to four weeks' duration. Specimens were examined for B. pertussis by PCR. Of 101 children with prolonged cough, 20 (19.8%) had a positive PCR testing for B. pertussis. Children who were vaccinated ≥5 years previously had a 6.13-fold higher risk of PCR-confirmed pertussis than those who were vaccinated < 5 years before. The classic symptoms of pertussis (paroxysmal cough, whooping and post-tussive vomiting) were seen in 30%, 15% and 25% of the patients with positive PCR, respectively; 55% of them had only a prolonged cough without any classic symptoms. Pertussis is common among Turkish children with prolonged cough, even after implementation of a fifth dose of pertussis vaccination and despite high vaccination coverage.

  20. Neurobehavioural Effects of Hypergravity Exposure in CD-1 Mice

    NASA Astrophysics Data System (ADS)

    Santucci, Daniela; Francia, Nadia; Aloe, Luigi; Enrico, Alleva

    The effects of spaceflight on the nervous system physiology could have important implications for the prolonged stay outside Earth's gravitational field. In this view, both ground-based and space research using animal models represent useful tools to investigate the impact of gravity (hypergravity, microgravity and weightlessness) on the nervous system and behaviour. Data coming from these studies, besides acquisition of knowledge relevant for spaceflights and pro-longed permanence of both humans and animals in space, could provide insight into basic bio-logical phenomena underlying the plasticity of the nervous system and its adaptive responses to a changing environment. Most ground experiments employing animal models use the paradigm of hypergravity exposure with the expectation that behavioural and physiological reactions to this environment might help to explain reactions to the microgravity challenge faced by or-biting animals. An overview of ground-based experiments set up to investigate the effects of changes of gravitational environment on the neurobehavioural responses of CD-1 mouse will be reported, and will illustrate the short-, medium-and long-term behavioural and neurobiological consequences of hypergravity exposure both at adulthood and during early and late postnatal development. Moreover, since mother-pup interaction is critical for the survival and the devel-opment of neonatal rodents, especially in an extreme environment such as that of space, we characterized, exploiting ethological methods, changes in maternal behaviour of CD-1 outbred mouse dams exposed to mild hypergravity. The results of these experiments will be discussed.