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Sample records for adversely affect sensitive

  1. FACTORS ADVERSELY AFFECTING AMPHIBIAN POPULATIONS IN THE US

    EPA Science Inventory

    Factors known or suspected to be adversely affecting native amphibian populations in the US were identified using information from species accounts written in a standardized format by multiple authors in a forthcoming book. Specific adverse factors were identified for 53 (58%) of...

  2. Parents' Psychiatric Issues May Adversely Affect Some Children

    MedlinePlus

    ... Adversely Affect Some Children History of antisocial disorder, suicide attempt or marijuana abuse showed the most effect, ... illness may be at higher risk for attempting suicide and/or engaging in violent behavior, a new ...

  3. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  4. Psychobiological influences on maternal sensitivity in the context of adversity.

    PubMed

    Finegood, Eric D; Blair, Clancy; Granger, Douglas A; Hibel, Leah C; Mills-Koonce, Roger

    2016-07-01

    This study evaluated prospective longitudinal relations among an index of poverty-related cumulative risk, maternal salivary cortisol, child negative affect, and maternal sensitivity across the first 2 postpartum years. Participants included 1,180 biological mothers residing in rural and predominantly low-income communities in the United States. Multilevel growth curve analyses indicated that an index of cumulative risk was positively associated with maternal cortisol across the postpartum (study visits occurring at approximately 7, 15, and 24 months postpartum) over and above effects for African American ethnicity, time of day of saliva collection, age, parity status, having given birth to another child, contraceptive use, tobacco smoking, body mass index, and breastfeeding. Consistent with a psychobiological theory of mothering, maternal salivary cortisol was negatively associated with maternal sensitivity observed during parent-child interactions across the first 2 postpartum years over and above effects for poverty-related cumulative risk, child negative affect, as well as a large number of covariates associated with cortisol and maternal sensitivity. Child negative affect expressed during parent-child interactions was negatively associated with observed maternal sensitivity at late (24 months) but not early time points of observation (7 months) and cumulative risk was negatively associated with maternal sensitivity across the postpartum and this effect strengthened over time. Results advance our understanding of the dynamic, transactional, and psychobiological influences on parental caregiving behaviors across the first 2 postpartum years. (PsycINFO Database Record PMID:27337514

  5. Psychobiological Influences on Maternal Sensitivity in the Context of Adversity

    ERIC Educational Resources Information Center

    Finegood, Eric D.; Blair, Clancy; Granger, Douglas A.; Hibel, Leah C.; Mills-Koonce, Roger

    2016-01-01

    This study evaluated prospective longitudinal relations among an index of poverty-related cumulative risk, maternal salivary cortisol, child negative affect, and maternal sensitivity across the first 2 postpartum years. Participants included 1,180 biological mothers residing in rural and predominantly low-income communities in the United States.…

  6. The synthetic progestin megestrol acetate adversely affects zebrafish reproduction.

    PubMed

    Han, Jian; Wang, Qiangwei; Wang, Xianfeng; Li, Yonggang; Wen, Sheng; Liu, Shan; Ying, Guangguo; Guo, Yongyong; Zhou, Bingsheng

    2014-05-01

    Synthetic progestins contaminate the aquatic ecosystem, and may cause adverse health effects on aquatic organisms. Megestrol acetate (MTA) is present in the aquatic environment, but its possible effects on fish reproduction are unknown. In the present study, we investigated the endocrine disruption and impact of MTA on fish reproduction. After a pre-exposure period of 14 days, reproductively mature zebrafish (Danio rerio) (F0) were exposed to MTA at environmental concentrations (33, 100, 333, and 666 ng/L) for 21 days. Egg production was decreased in F0 fish exposed to MTA, with a significant decrease at 666 ng/L. The exposure significantly decreased the circulating concentrations of estradiol (E2) and testosterone (T) in female fish or 11-keto testosterone (11-KT) in male fish. MTA exposure significantly downregulated the transcription of certain genes along the hypothalamic-pituitary-gonadal (HPG) axis. MTA did not affect early embryonic development or hatching success in the F1 generation. The present study showed that MTA is a potent endocrine disruptor in fish, and short-term exposure to MTA could significantly affect reproduction in fish and negatively impact the fish population. PMID:24647012

  7. The synthetic progestin megestrol acetate adversely affects zebrafish reproduction.

    PubMed

    Han, Jian; Wang, Qiangwei; Wang, Xianfeng; Li, Yonggang; Wen, Sheng; Liu, Shan; Ying, Guangguo; Guo, Yongyong; Zhou, Bingsheng

    2014-05-01

    Synthetic progestins contaminate the aquatic ecosystem, and may cause adverse health effects on aquatic organisms. Megestrol acetate (MTA) is present in the aquatic environment, but its possible effects on fish reproduction are unknown. In the present study, we investigated the endocrine disruption and impact of MTA on fish reproduction. After a pre-exposure period of 14 days, reproductively mature zebrafish (Danio rerio) (F0) were exposed to MTA at environmental concentrations (33, 100, 333, and 666 ng/L) for 21 days. Egg production was decreased in F0 fish exposed to MTA, with a significant decrease at 666 ng/L. The exposure significantly decreased the circulating concentrations of estradiol (E2) and testosterone (T) in female fish or 11-keto testosterone (11-KT) in male fish. MTA exposure significantly downregulated the transcription of certain genes along the hypothalamic-pituitary-gonadal (HPG) axis. MTA did not affect early embryonic development or hatching success in the F1 generation. The present study showed that MTA is a potent endocrine disruptor in fish, and short-term exposure to MTA could significantly affect reproduction in fish and negatively impact the fish population.

  8. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

  9. Shrub clearing adversely affects the abundance of Ixodes ricinus ticks.

    PubMed

    Tack, Wesley; Madder, Maxime; Baeten, Lander; Vanhellemont, Margot; Verheyen, Kris

    2013-07-01

    In order to get a better understanding of the importance of vertical forest structure as a component of Ixodes ricinus tick habitat, an experiment was set up in a coniferous forest on sandy soils in northern Belgium. Ticks were sampled in six control and six treatment plots on various sampling occasions in 2008-2010. In the course of the study period, a moderate thinning was carried out in all plots and shrub clearing was performed in the treatment plots. Thinning had no effect on tick abundance, while shrub clearing had an adverse affect on the abundance of all three life stages (larva, nymph, adult) up to 2 years post-clearing. Our findings are especially relevant in the light of the ongoing efforts to improve vertical forest structure in Belgium and many other parts of Europe, which might create suitable habitats for ticks and change the epidemiology of tick-borne diseases. Also, our results indicate that shrub clearing could be applied as a tick control measure in recreational areas where there is a high degree of human-tick contact.

  10. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  11. Root-Zone Glyphosate Exposure Adversely Affects Two Ditch Species

    PubMed Central

    Saunders, Lyndsay E.; Koontz, Melissa B.; Pezeshki, Reza

    2013-01-01

    Glyphosate, one of the most applied herbicides globally, has been extensively studied for its effects on non-target organisms. In the field, following precipitation, glyphosate runs off into agricultural ditches where it infiltrates into the soil and thus may encounter the roots of vegetation. These edge-of-field ditches share many characteristics with wetlands, including the ability to reduce loads of anthropogenic chemicals through uptake, transformation, and retention. Different species within the ditches may have a differential sensitivity to exposure of the root zone to glyphosate, contributing to patterns of abundance of ruderal species. The present laboratory experiment investigated whether two species commonly found in agricultural ditches in southcentral United States were affected by root zone glyphosate in a dose-dependent manner, with the objective of identifying a sublethal concentration threshold. The root zone of individuals of Polygonum hydropiperoides and Panicum hemitomon were exposed to four concentrations of glyphosate. Leaf chlorophyll content was measured, and the ratio of aboveground biomass to belowground biomass and survival were quantified. The findings from this study showed that root zone glyphosate exposure negatively affected both species including dose-dependent reductions in chlorophyll content. P. hydropiperdoides showed the greatest negative response, with decreased belowground biomass allocation and total mortality at the highest concentrations tested. PMID:24833234

  12. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA.

  13. Why Does Military Combat Experience Adversely Affect Marital Relations?

    ERIC Educational Resources Information Center

    Gimbel, Cynthia; Booth, Alan

    1994-01-01

    Describes investigation of ways in which combat decreases marital quality and stability. Results support three models: (1) factors propelling men into combat also make them poor marriage material; (2) combat causes problems that increase marital adversity; and (3) combat intensifies premilitary stress and antisocial behavior which then negatively…

  14. The negative affect hypothesis of noise sensitivity.

    PubMed

    Shepherd, Daniel; Heinonen-Guzejev, Marja; Heikkilä, Kauko; Dirks, Kim N; Hautus, Michael J; Welch, David; McBride, David

    2015-05-01

    Some studies indicate that noise sensitivity is explained by negative affect, a dispositional tendency to negatively evaluate situations and the self. Individuals high in such traits may report a greater sensitivity to other sensory stimuli, such as smell, bright light and pain. However, research investigating the relationship between noise sensitivity and sensitivity to stimuli associated with other sensory modalities has not always supported the notion of a common underlying trait, such as negative affect, driving them. Additionally, other explanations of noise sensitivity based on cognitive processes have existed in the clinical literature for over 50 years. Here, we report on secondary analyses of pre-existing laboratory (n = 74) and epidemiological (n = 1005) data focusing on the relationship between noise sensitivity to and annoyance with a variety of olfactory-related stimuli. In the first study a correlational design examined the relationships between noise sensitivity, noise annoyance, and perceptual ratings of 16 odors. The second study sought differences between mean noise and air pollution annoyance scores across noise sensitivity categories. Results from both analyses failed to support the notion that, by itself, negative affectivity explains sensitivity to noise.

  15. The Negative Affect Hypothesis of Noise Sensitivity

    PubMed Central

    Shepherd, Daniel; Heinonen-Guzejev, Marja; Heikkilä, Kauko; Dirks, Kim N.; Hautus, Michael J.; Welch, David; McBride, David

    2015-01-01

    Some studies indicate that noise sensitivity is explained by negative affect, a dispositional tendency to negatively evaluate situations and the self. Individuals high in such traits may report a greater sensitivity to other sensory stimuli, such as smell, bright light and pain. However, research investigating the relationship between noise sensitivity and sensitivity to stimuli associated with other sensory modalities has not always supported the notion of a common underlying trait, such as negative affect, driving them. Additionally, other explanations of noise sensitivity based on cognitive processes have existed in the clinical literature for over 50 years. Here, we report on secondary analyses of pre-existing laboratory (n = 74) and epidemiological (n = 1005) data focusing on the relationship between noise sensitivity to and annoyance with a variety of olfactory-related stimuli. In the first study a correlational design examined the relationships between noise sensitivity, noise annoyance, and perceptual ratings of 16 odors. The second study sought differences between mean noise and air pollution annoyance scores across noise sensitivity categories. Results from both analyses failed to support the notion that, by itself, negative affectivity explains sensitivity to noise. PMID:25993104

  16. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  17. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC...

  18. Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

    PubMed Central

    Thomas, Melanie; Wara, Diane; Saxton, Katherine; Truskier, Mary; Chesney, Margaret; Boyce, W. Thomas

    2013-01-01

    Objective To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. Methods Data from 38 HIV+ and 29 HIV− children born to seropositive women were obtained before and after school entry. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity (based on mean arterial responses to challenge tasks), and enumerative and functional changes in peripheral blood immune parameters. Results In comparison to children who were HIV−, children who were HIV+ at baseline had fewer CD4+ T lymphocytes (M = 916 vs. 1206 cells/mm3 × 103; F = 7.8, p = .007), more CD8+ cells (M = 1046 vs. 720 cells/mm3 ×103; F = 7.98, p = .006), and diminished NK cell cytotoxicity (M =−.29 vs. .41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters following school entry were associated with family stress and pre school entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8+ cells following school entry or the greatest decrease, depending upon reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. Conclusions These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV. PMID:23766380

  19. Urban sprawl and you: how sprawl adversely affects worker health.

    PubMed

    Pohanka, Mary; Fitzgerald, Sheila

    2004-06-01

    Urban sprawl, once thought of as just an environmental issue, is currently gaining momentum as an emerging public health issue worthy of research and political attention. Characteristics seen in sprawling communities include increasing traffic volumes; inadequate public transportation; pedestrian unfriendly streets; and the division of businesses, shops, and homes. These characteristics can affect health in many ways. Greater air pollution contributes to higher asthma and other lung disorder rates. An increased dependence on the automobile encourages a more sedentary lifestyle and can potentially contribute to obesity. The increased danger and stress of long commutes can lead to more accidents, anxiety, and social isolation. Occupational health nurses can become involved by promoting physical activity in the workplace, creating programs for injury prevention and stress management, becoming involved in political smart growth measures, and educating and encouraging colleagues to become active in addressing this issue.

  20. ABSENCE OF SCLEROSTIN ADVERSELY AFFECTS B CELL SURVIVAL

    PubMed Central

    Cain, Corey J.; Rueda, Randell; McLelland, Bryce; Collette, Nicole M.; Loots, Gabriela G.; Manilay, Jennifer O.

    2012-01-01

    Increased osteoblast activity in sclerostin-knockout (Sost−/−) mice results in generalized hyperostosis and bones with small bone marrow cavities due to hyperactive mineralizing osteoblast populations. Hematopoietic cell fate decisions are dependent on their local microenvironment, which contains osteoblast and stromal cell populations that support both hematopoietic stem cell quiescence and facilitate B cell development. In this study, we investigated whether high bone mass environments affect B cell development via the utilization of Sost−/− mice, a model of sclerosteosis. We found the bone marrow of Sost−/− mice to be specifically depleted of B cells, due to elevated apoptosis at all B cell developmental stages. In contrast, B cell function in the spleen was normal. Sost expression analysis confirmed that Sost is primarily expressed in osteocytes and is not expressed in any hematopoietic lineage, which indicated that the B cell defects in Sost−/− mice are non-cell autonomous and this was confirmed by transplantation of wildtype (WT) bone marrow into lethally irradiated Sost−/− recipients. WT→Sost−/− chimeras displayed a reduction in B cells, whereas reciprocal Sost−/−→WT chimeras did not, supporting the idea that the Sost−/− bone environment cannot fully support normal B cell development. Expression of the pre-B cell growth stimulating factor, Cxcl12, was significantly lower in bone marrow stromal cells of Sost−/− mice while the Wnt target genes Lef-1 and Ccnd1 remained unchanged in B cells. Taken together, these results demonstrate a novel role for Sost in the regulation of bone marrow environments that support B cells. PMID:22434688

  1. Cumulative Adversity Sensitizes Neural Response to Acute Stress: Association with Health Symptoms

    PubMed Central

    Seo, Dongju; Tsou, Kristen A; Ansell, Emily B; Potenza, Marc N; Sinha, Rajita

    2014-01-01

    Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic–striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences. PMID:24051900

  2. Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens.

    PubMed

    Sastre, J; Rodríguez, F; Campo, P; Laffond, E; Marín, A; Alonso, M D

    2015-05-01

    The aim of the study was to investigate whether adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ® Phleum, ALK-Abelló) are related to the different patterns of sensitization of patients to grass allergens. A total of 192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4-week updosing with five injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association between the number of grass allergens that sensitized the patients and the total number of ADRs (P = 0.004) occurred locally (P = 0.003) and systemically (P = 0.01). Sensitization to Phl p1 + Phl p5 or Phl p1 + Phl p5 + Phl p12 was significantly associated with a higher frequency of local or systemic reactions (P = 0.001, both). Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy.

  3. Vestibular stimulation affects optic-flow sensitivity.

    PubMed

    Edwards, Mark; O'Mahony, Simon; Ibbotson, Michael R; Kohlhagen, Stuart

    2010-01-01

    Typically, multiple cues can be used to generate a particular percept. Our area of interest is the extent to which humans are able to synergistically combine cues that are generated when moving through an environment. For example, movement through the environment leads to both visual (optic-flow) and vestibular stimulation, and studies have shown that non-human primates are able to combine these cues to generate a more accurate perception of heading than can be obtained with either cue in isolation. Here we investigate whether humans show a similar ability to synergistically combine optic-flow and vestibular cues. This was achieved by determining the sensitivity to optic-flow stimuli while physically moving the observer, and hence producing a vestibular signal, that was either consistent with the optic-flow signal, eg a radially expanding pattern coupled with forward motion, or inconsistent with it, eg a radially expanding pattern with backward motion. Results indicate that humans are more sensitive to motion-in-depth optic-flow stimuli when they are combined with complementary vestibular signals than when they are combined with conflicting vestibular signals. These results indicate that in humans, like in nonhuman primates, there is perceptual integration of visual and vestibular signals. PMID:21180352

  4. 42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435... another compact, funding agreement, or construction project agreement. ... appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations, or...

  5. 42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435... another compact, funding agreement, or construction project agreement. ... appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations, or...

  6. 42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435... another compact, funding agreement, or construction project agreement. ... appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations, or...

  7. 42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435... another compact, funding agreement, or construction project agreement. ... appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations, or...

  8. 42 CFR 137.435 - Will an appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... rights in other compact, funding negotiations, or construction project agreement? 137.435 Section 137.435... another compact, funding agreement, or construction project agreement. ... appeal adversely affect the Indian Tribe's rights in other compact, funding negotiations, or...

  9. Dietary restriction does not adversely affect bone geometry and mechanics in rapidly growing male wistar rats.

    PubMed

    Lambert, Jennifer; Lamothe, Jeremy M; Zernicke, Ronald F; Auer, Roland N; Reimer, Raylene A

    2005-02-01

    The present study assessed the effects of dietary restriction on tibial and vertebral mechanical and geometrical properties in 2-mo-old male Wistar rats. Two-month-old male Wistar rats were randomized to the ad libitum (n=8) or the 35% diet-restricted (DR) feeding group (n=9) for 5 mo. Tibiae and L6 vertebrae were dissected out for microcomputed tomography (microCT) scanning and subsequently fractured in biomechanical testing to determine geometrical and mechanical properties. The DR group had significantly lower mean tibial length, mass, area, and cross-sectional moment of inertia, as well as vertebral energy to maximal load. After adjustment for body mass, however, DR tibial mean maximal load and stiffness, and DR vertebral area, height, volume, and maximal load were significantly greater, relative to ad libitum means. No significant differences were found between the DR and ad libitum mineral ash fractions. Because the material properties of the tibiae between the two groups were not significantly different, presumably the material integrity of the bones was not adversely affected as a consequence of DR. The similar material characteristics were consistent with mineral ash fractions that were not different between the two groups. Vertebral maximal load and stiffness were not significant between the DR and ad libitum animals. Importantly, we show that a level of dietary restriction (35%) that is less severe than many studies (40%), and without micronutrient compensation does not adversely affect tibial and vertebral mechanical properties in young growing male rats when normalized for body mass. PMID:15585686

  10. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  11. Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

    PubMed Central

    Davis, Elysia Poggi; Pfaff, Donald

    2014-01-01

    During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

  12. 30 CFR 285.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... conditions adversely affect a cable, pipeline, or facility? 285.816 Section 285.816 Mineral Resources BUREAU... other conditions adversely affect a cable, pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or facility so as to endanger the safety or the environment, you...

  13. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  14. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  15. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  16. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  17. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  18. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH.

    PubMed

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification. PMID:26740396

  19. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH.

    PubMed

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-07

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification.

  20. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH

    PubMed Central

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification. PMID:26740396

  1. Early Life in a Barren Environment Adversely Affects Spatial Cognition in Laying Hens (Gallus gallus domesticus).

    PubMed

    Tahamtani, Fernanda M; Nordgreen, Janicke; Nordquist, Rebecca E; Janczak, Andrew M

    2015-01-01

    Spatial cognition in vertebrates is adversely affected by a lack of environmental complexity during early life. However, to our knowledge, no previous studies have tested the effect of early exposure to varying degrees of environmental complexity on specific components of spatial cognition in chickens. There are two main rearing systems for laying hens in the EU: aviaries and cages. These two systems differ from one another in environmental complexity. The aim of the present study was to test the hypothesis that rearing in a barren cage environment relative to a complex aviary environment causes long-lasting deficits in the ability to perform spatial tasks. For this purpose, 24 white Dekalb laying hens, half of which had been reared in an aviary system and the other half in a conventional cage system, were tested in a holeboard task. Birds from both treatment groups learnt the task; however, the cage-reared hens required more time to locate rewards and had poorer levels of working memory. The latter finding supports the hypothesis that rearing in a barren environment causes long-term impairment of short-term memory in chickens. PMID:26664932

  2. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed.

  3. Early Life in a Barren Environment Adversely Affects Spatial Cognition in Laying Hens (Gallus gallus domesticus)

    PubMed Central

    Tahamtani, Fernanda M.; Nordgreen, Janicke; Nordquist, Rebecca E.; Janczak, Andrew M.

    2015-01-01

    Spatial cognition in vertebrates is adversely affected by a lack of environmental complexity during early life. However, to our knowledge, no previous studies have tested the effect of early exposure to varying degrees of environmental complexity on specific components of spatial cognition in chickens. There are two main rearing systems for laying hens in the EU: aviaries and cages. These two systems differ from one another in environmental complexity. The aim of the present study was to test the hypothesis that rearing in a barren cage environment relative to a complex aviary environment causes long-lasting deficits in the ability to perform spatial tasks. For this purpose, 24 white Dekalb laying hens, half of which had been reared in an aviary system and the other half in a conventional cage system, were tested in a holeboard task. Birds from both treatment groups learnt the task; however, the cage-reared hens required more time to locate rewards and had poorer levels of working memory. The latter finding supports the hypothesis that rearing in a barren environment causes long-term impairment of short-term memory in chickens. PMID:26664932

  4. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture.

  5. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  6. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees

    PubMed Central

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-01-01

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  7. Probabilities of adverse weather affecting transport in Europe: climatology and scenarios up to the 2050s

    NASA Astrophysics Data System (ADS)

    Vajda, A.; Tuomenvirta, H.; Jokinen, P.; Luomaranta, A.; Makkonen, L.; Tikanmäki, M.; Groenemeijer, P.; Saarikivi, P.; Michaelides, S.; Papadakis, M.; Tymvios, F.; Athanasatos, S.

    2012-04-01

    This paper provides the first comprehensive climatology of the adverse and extreme weather events affecting the European transport system by estimating the frequency (or probability) of phenomena for the present climate (1971-2000) and an overview of the projected changes in some of these extremes in the future climate until the 2050s. The research was carried out within the framework of the EWENT Project that addresses the European Union (EU) policies and strategies related to climate change, with a particular focus on extreme weather impacts on the EU transportation system. This project is funded by the Seventh Framework Programme (Transports, call ID FPT7-TPT-2008-RTD-1). The analyzed phenomena are wind, snow, blizzards, heavy precipitation, cold spells and heat waves. In addition, reduced visibility conditions determined by fog and dust events, small-scale phenomena affecting the transport system, such as thunderstorms, lightning, large hail and tornadoes and events damaging infrastructure of the transport system, have been considered. Frequency and probability analysis of past and present ex¬tremes were performed using observational and atmospheric reanalysis data. Future changes in the probability of severe events were assessed based on six regional climate model simulations produced in the FP6 ENSEMBLES project (http://www.ensembles-eu.org/). To facilitate the assessment of impacts and consequences of extreme phenomena on a continental level, the WP2 Deliverable introduces a regionalization of the European extreme phenomena, defining the climate zones with similarities in extreme phenomena. The projected changes as well as large natural variability in weather extremes on the transportation network will have impacts of both signs. The decline of extreme cold and snowfall over most of the continent implies a positive impact on road, rail, inland water and air transportation, e.g., by reducing snow removal. However, even with a general decreasing trend in

  8. 41 CFR 102-78.40 - What responsibilities do Federal agencies have when an undertaking adversely affects a historic...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Federal agencies have when an undertaking adversely affects a historic or cultural property? 102-78.40... or cultural property? Federal agencies must not perform an undertaking that could alter, destroy, or modify an historic or cultural property until they have consulted with the SHPO and the Advisory...

  9. 41 CFR 102-78.40 - What responsibilities do Federal agencies have when an undertaking adversely affects a historic...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... guidance on the protection of historic and cultural properties in 36 CFR part 800. ... Federal agencies have when an undertaking adversely affects a historic or cultural property? 102-78.40... (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 78-HISTORIC PRESERVATION Historic Preservation §...

  10. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  11. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  12. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  13. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro.

    PubMed

    Fan, Lir-Wan; Bhatt, Abhay; Tien, Lu-Tai; Zheng, Baoying; Simpson, Kimberly L; Lin, Rick C S; Cai, Zhengwei; Kumar, Praveen; Pang, Yi

    2015-05-01

    patterns of contactin-associated protein (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that 5-HT exposure may affect other axon-derived factors for myelination. In summary, this is the first study to demonstrate that manipulation of serotonin levels affects OL development and myelination, which may contribute to altered neural connectivity noted in SSRIs-treated animals. The current in vitro study demonstrated that exposure to high level of serotonin (5-HT) led to aberrant oligodendrocyte (OL) development, cell injury, and myelination deficit. We propose that elevated extracellular serotonin levels in the fetal brain, such as upon the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, may adversely affect OL development and/or myelination, thus contributing to altered neural connectivity seen in Autism Spectrum Disorders. OPC = oligodendrocyte progenitor cell.

  14. Reinforcement sensitivity underlying treatment-seeking smokers' affect, smoking reinforcement motives, and affective responses.

    PubMed

    Cui, Yong; Robinson, Jason D; Engelmann, Jeffrey M; Lam, Cho Y; Minnix, Jennifer A; Karam-Hage, Maher; Wetter, David W; Dani, John A; Kosten, Thomas R; Cinciripini, Paul M

    2015-06-01

    Nicotine dependence has been suggested to be related to reinforcement sensitivity, which encompasses behavioral predispositions either to avoid aversive (behavioral inhibition) or to approach appetitive (behavioral activation) stimuli. Reinforcement sensitivity may shape motives for nicotine use and offer potential targets for personalized smoking cessation therapy. However, little is known regarding how reinforcement sensitivity is related to motivational processes implicated in the maintenance of smoking. Additionally, women and men differ in reinforcement sensitivity, and such difference may cause distinct relationships between reinforcement sensitivity and motivational processes for female and male smokers. In this study, the authors characterized reinforcement sensitivity in relation to affect, smoking-related reinforcement motives, and affective responses, using self-report and psychophysiological measures, in over 200 smokers before treating them. The Behavioral Inhibition/Activation Scales (BIS/BAS; Carver & White, 1994) was used to measure reinforcement sensitivity. In female and male smokers, BIS was similarly associated with negative affect and negative reinforcement of smoking. However, positive affect was positively associated with BAS Drive scores in male smokers, and this association was reversed in female smokers. BIS was positively associated with corrugator electromyographic reactivity toward negative stimuli and left frontal electroencephalogram alpha asymmetry. Female and male smokers showed similar relationships for these physiological measures. These findings suggest that reinforcement sensitivity underpins important motivational processes (e.g., affect), and gender is a moderating factor for these relationships. Future personalized smoking intervention, particularly among more dependent treatment-seeking smokers, may experiment to target individual differences in reinforcement sensitivity. (PsycINFO Database Record PMID:25621416

  15. Reinforcement sensitivity underlying treatment-seeking smokers' affect, smoking reinforcement motives, and affective responses.

    PubMed

    Cui, Yong; Robinson, Jason D; Engelmann, Jeffrey M; Lam, Cho Y; Minnix, Jennifer A; Karam-Hage, Maher; Wetter, David W; Dani, John A; Kosten, Thomas R; Cinciripini, Paul M

    2015-06-01

    Nicotine dependence has been suggested to be related to reinforcement sensitivity, which encompasses behavioral predispositions either to avoid aversive (behavioral inhibition) or to approach appetitive (behavioral activation) stimuli. Reinforcement sensitivity may shape motives for nicotine use and offer potential targets for personalized smoking cessation therapy. However, little is known regarding how reinforcement sensitivity is related to motivational processes implicated in the maintenance of smoking. Additionally, women and men differ in reinforcement sensitivity, and such difference may cause distinct relationships between reinforcement sensitivity and motivational processes for female and male smokers. In this study, the authors characterized reinforcement sensitivity in relation to affect, smoking-related reinforcement motives, and affective responses, using self-report and psychophysiological measures, in over 200 smokers before treating them. The Behavioral Inhibition/Activation Scales (BIS/BAS; Carver & White, 1994) was used to measure reinforcement sensitivity. In female and male smokers, BIS was similarly associated with negative affect and negative reinforcement of smoking. However, positive affect was positively associated with BAS Drive scores in male smokers, and this association was reversed in female smokers. BIS was positively associated with corrugator electromyographic reactivity toward negative stimuli and left frontal electroencephalogram alpha asymmetry. Female and male smokers showed similar relationships for these physiological measures. These findings suggest that reinforcement sensitivity underpins important motivational processes (e.g., affect), and gender is a moderating factor for these relationships. Future personalized smoking intervention, particularly among more dependent treatment-seeking smokers, may experiment to target individual differences in reinforcement sensitivity. (PsycINFO Database Record

  16. Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation

    PubMed Central

    ASTOLFI, LAURA; GHISELLI, SARA; GUARAN, VALERIA; CHICCA, MILVIA; SIMONI, EDI; OLIVETTO, ELENA; LELLI, GIORGIO; MARTINI, ALESSANDRO

    2013-01-01

    Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered. PMID:23404427

  17. Secreted biofilm factors adversely affect cellular wound healing responses in vitro.

    PubMed

    Jeffery Marano, Robert; Jane Wallace, Hilary; Wijeratne, Dulharie; William Fear, Mark; San Wong, Hui; O'Handley, Ryan

    2015-08-17

    Although most chronic wounds possess an underlying pathology, infectious agents also contribute. In many instances, pathogens exist as biofilms forming clusters surrounded by a secreted extracellular substance. We hypothesized that compounds secreted by biofilm bacteria may inhibit normal wound healing events including cell proliferation and migration. Conditioned media from two common bacterial species associated with chronic skin wounds and chronic tympanic membrane perforations, Staphylococcus aureus and Pseudomonas aeruginosa, were evaluated for their capacity to affect keratinocyte proliferation and migration. Additionally, proteomic analysis was performed to identify proteins within the biofilm conditioned media that may contribute to these observed effects. Biofilm conditioned media from both species inhibited proliferation in human tympanic membrane derived keratinocytes, whereas only biofilm conditioned media from S. aureus inhibited migration. Human epidermal keratinocytes were found to be more sensitive to the effects of the conditioned media resulting in high levels of cell death. Heat treatment and microfiltration suggested that S. aureus activity was due to a protein, while P. aeruginosa activity was more likely due to a small molecule. Proteomic analysis identified several proteins with putative links to delayed wound healing. These include alpha hemolysin, alcohol dehydrogenase, fructose-bisphosphate aldolase, lactate dehydrogenase and epidermal cell differentiation inhibitor.

  18. Secreted biofilm factors adversely affect cellular wound healing responses in vitro.

    PubMed

    Jeffery Marano, Robert; Jane Wallace, Hilary; Wijeratne, Dulharie; William Fear, Mark; San Wong, Hui; O'Handley, Ryan

    2015-01-01

    Although most chronic wounds possess an underlying pathology, infectious agents also contribute. In many instances, pathogens exist as biofilms forming clusters surrounded by a secreted extracellular substance. We hypothesized that compounds secreted by biofilm bacteria may inhibit normal wound healing events including cell proliferation and migration. Conditioned media from two common bacterial species associated with chronic skin wounds and chronic tympanic membrane perforations, Staphylococcus aureus and Pseudomonas aeruginosa, were evaluated for their capacity to affect keratinocyte proliferation and migration. Additionally, proteomic analysis was performed to identify proteins within the biofilm conditioned media that may contribute to these observed effects. Biofilm conditioned media from both species inhibited proliferation in human tympanic membrane derived keratinocytes, whereas only biofilm conditioned media from S. aureus inhibited migration. Human epidermal keratinocytes were found to be more sensitive to the effects of the conditioned media resulting in high levels of cell death. Heat treatment and microfiltration suggested that S. aureus activity was due to a protein, while P. aeruginosa activity was more likely due to a small molecule. Proteomic analysis identified several proteins with putative links to delayed wound healing. These include alpha hemolysin, alcohol dehydrogenase, fructose-bisphosphate aldolase, lactate dehydrogenase and epidermal cell differentiation inhibitor. PMID:26278131

  19. Severe Affective and Behavioural Dysregulation Is Associated with Significant Psychosocial Adversity and Impairment

    ERIC Educational Resources Information Center

    Jucksch, Viola; Salbach-Andrae, Harriet; Lenz, Klaus; Goth, Kirstin; Dopfner, Manfred; Poustka, Fritz; Freitag, Christine M.; Lehmkuhl, Gerd; Lehmkuhl, Ulrike; Holtmann, Martin

    2011-01-01

    Background: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP.…

  20. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... affect a cable, pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or facility so as to endanger the safety or the environment, you must: (a) Submit a plan...

  1. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... affect a cable, pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or facility so as to endanger the safety or the environment, you must: (a) Submit a plan...

  2. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... affect a cable, pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or facility so as to endanger the safety or the environment, you must: (a) Submit a plan...

  3. Affective state influences perception by affecting decision parameters underlying bias and sensitivity.

    PubMed

    Lynn, Spencer K; Zhang, Xuan; Barrett, Lisa Feldman

    2012-08-01

    Studies of the effect of affect on perception often show consistent directional effects of a person's affective state on perception. Unpleasant emotions have been associated with a "locally focused" style of stimulus evaluation, and positive emotions with a "globally focused" style. Typically, however, studies of affect and perception have not been conducted under the conditions of perceptual uncertainty and behavioral risk inherent to perceptual judgments outside the laboratory. We investigated the influence of perceivers' experienced affect (valence and arousal) on the utility of social threat perception by combining signal detection theory and behavioral economics. We compared 3 perceptual decision environments that systematically differed with respect to factors that underlie uncertainty and risk: the base rate of threat, the costs of incorrect identification threat, and the perceptual similarity of threats and nonthreats. We found that no single affective state yielded the best performance on the threat perception task across the 3 environments. Unpleasant valence promoted calibration of response bias to base rate and costs, high arousal promoted calibration of perceptual sensitivity to perceptual similarity, and low arousal was associated with an optimal adjustment of bias to sensitivity. However, the strength of these associations was conditional upon the difficulty of attaining optimal bias and high sensitivity, such that the effect of the perceiver's affective state on perception differed with the cause and/or level of uncertainty and risk.

  4. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

    ERIC Educational Resources Information Center

    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  5. Hunger state affects both olfactory abilities and gustatory sensitivity.

    PubMed

    Hanci, Deniz; Altun, Huseyin

    2016-07-01

    Chemical senses such as odor, taste and appearance are directly related with appetite. Understanding the relation between appetite and flavor is getting more important due to increasing number of obese patients worldwide. The literature on the studies investigating the change in olfactory abilities and gustatory sensitivity mostly performed using food-related odors and tastes rather than standardized tests were developed to study olfaction and gustation. Therefore, results are inconsistent and the relationship between olfactory and gustatory sensitivity with respect to the actual state of human satiety is still not completely understood. Here, for the first time in literature, we investigated the change in both olfactory abilities and gustatory sensitivity in hunger and in satiety using 123 subjects (37 men, 86 women; mean age 31.4 years, age range 21-41 years). The standardized Sniffin' Sticks Extended Test and Taste Strips were used for olfactory testing and gustatory sensitivity, respectively. TDI score (range 1-48) was calculated as the collective scores of odor threshold (T), odor discrimination (D) and odor identification (I). The evaluation was performed in two successive days where the hunger state of test subjects was confirmed by blood glucose test strips (mean blood glucose level 90.0 ± 5.6 mg/dl in hunger and 131.4 ± 8.1 mg/dl in satiety). The results indicated statistically significant decrease in olfaction in satiety compared to hunger (mean TDI 39.3 ± 1.1 in hunger, 37.4 ± 1.1 in satiety, p < 0.001). The comparison of gustatory sensitivity indicated significantly higher sensitivity to sweet, sour and salty in hunger (p < 0.001), but significantly higher sensitivity to bitter tastant in satiety (p < 0.001). With this prospective study, we were able to show that both olfactory abilities and gustatory sensitivity were affected by hunger state.

  6. 30 CFR 285.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility? 285.816 Section 285.816 Mineral Resources..., pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or...

  7. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  8. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  9. Adverse childhood experiences associate to reduced glutamate levels in the hippocampus of patients affected by mood disorders.

    PubMed

    Poletti, Sara; Locatelli, Clara; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

    2016-11-01

    Adverse childhood experiences (ACE) can possibly permanently alter the stress response system, affect the glutamatergic system and influence hippocampal volume in mood disorders. The aim of the study is to investigate the association between glutamate levels in the hippocampus, measured through single proton magnetic resonance spectroscopy (1H-MRS), and ACE in patients affected by mood disorders and healthy controls. Higher levels of early stress associate to reduced levels of Glx/Cr in the hippocampus in depressed patients but not in healthy controls. Exposure to stress during early life could lead to a hypofunctionality of the glutamatergic system in the hippocampus of depressed patients. Abnormalities of glutamatergic signaling could then possibly underpin the structural and functional abnormalities observed in patients affected by mood disorders.

  10. Coral and mollusc resistance to ocean acidification adversely affected by warming

    NASA Astrophysics Data System (ADS)

    Rodolfo-Metalpa, R.; Houlbrèque, F.; Tambutté, É.; Boisson, F.; Baggini, C.; Patti, F. P.; Jeffree, R.; Fine, M.; Foggo, A.; Gattuso, J.-P.; Hall-Spencer, J. M.

    2011-09-01

    Increasing atmospheric carbon dioxide (CO2) concentrations are expectedto decrease surface ocean pH by 0.3-0.5 units by 2100 (refs , ), lowering the carbonate ion concentration of surfacewaters. This rapid acidification is predicted to dramatically decrease calcification in many marine organisms. Reduced skeletal growth under increased CO2 levels has already been shown for corals, molluscs and many other marine organisms. The impact of acidification on the ability of individual species to calcify has remained elusive, however, as measuring net calcification fails to disentangle the relative contributions of gross calcification and dissolution rates on growth. Here, we show that corals and molluscs transplanted along gradients of carbonate saturation state at Mediterranean CO2 vents are able to calcify and grow at even faster than normal rates when exposed to the high CO2 levels projected for the next 300 years. Calcifiers remain at risk, however, owing to the dissolution of exposed shells and skeletons that occurs as pH levels fall. Our results show that tissues and external organic layers play a major role in protecting shells and skeletons from corrosive sea water, limiting dissolution and allowing organisms to calcify. Our combined field and laboratory results demonstrate that the adverse effects of global warming are exacerbated when high temperatures coincide with acidification.

  11. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  12. Factors affecting sensitivity and specificity of a diagnostic test: the exercise thallium scintigram

    SciTech Connect

    Detrano, R.; Janosi, A.; Lyons, K.P.; Marcondes, G.; Abbassi, N.; Froelicher, V.F.

    1988-04-01

    Technical and methodological factors might affect the reported accuracies of diagnostic tests. To assess their influence on the accuracy of exercise thallium scintigraphy, the medical literature (1977 to 1986) was non-selectively searched and meta-analysis was applied to the 56 publications thus retrieved. These were analyzed for year of publication, sex and mean age of patients, percentage of patients with angina pectoris, percentage of patients with prior myocardial infarction, percentage of patients taking beta-blocking medications, and for angiographic referral (workup) bias, blinding of tests, and technical factors. The percentage of patients with myocardial infarction had the highest correlation with sensitivity (0.45, p = 0.0007). Only the inclusion of subjects with prior infarction and the percentage of men in the study group were independently and significantly (p less than 0.05) related to test sensitivity. Both the presence of workup bias and publication year adversely affected specificity (p less than 0.05). Of these two factors, publication year had the strongest association by stepwise linear regression. This analysis suggests that the reported sensitivity of thallium scintigraphy is higher and the specificity lower than that expected in clinical practice because of the presence of workup bias and the inappropriate inclusion of post-infarct patients.

  13. Factors Affecting the Sensitivity of Permafrost to Climate Change

    NASA Astrophysics Data System (ADS)

    Jorgenson, T.; Romanovsky, V.; Harden, J.; Shur, Y.; Hinzman, L.; Marchenko, S.; Bolton, R.; O'Donnell, J.

    2009-05-01

    degradation when water is impounded in sinking depressions. Thus, the amount of ground ice and potential thaw settlement greatly affects permafrost sensitivity. Water bodies (lakes, ponds, rivers) have a warming effect on permafrost and often create thawing zones for which their geometry is defined by water depth, sediment texture, and climate. Convective heat transfer associated with groundwater movement can create an unfrozen zone on top or within permafrost. Surface and groundwater flow, and surface impoundment, in turn are affected by topography and soil texture. Because permafrost is greatly affected by these ecological components, permafrost properties evolve along with the successional patterns of ecosystem development, which in turn affects the sensitivity of permafrost to degradation. We explore the relative effects of these factors through modeling and comparison of field measurements. Because there is no single model available that can include all these disparate factors, we evaluate factors separately and use differences in mean annual ground temperatures at the surface and at 2-m depth to compare the magnitude of each effect.

  14. Aspergillus nidulans galactofuranose biosynthesis affects antifungal drug sensitivity.

    PubMed

    Alam, Md Kausar; El-Ganiny, Amira M; Afroz, Sharmin; Sanders, David A R; Liu, Juxin; Kaminskyj, Susan G W

    2012-12-01

    The cell wall is essential for fungal survival in natural environments. Many fungal wall carbohydrates are absent from humans, so they are a promising source of antifungal drug targets. Galactofuranose (Galf) is a sugar that decorates certain carbohydrates and lipids. It comprises about 5% of the Aspergillus fumigatus cell wall, and may play a role in systemic aspergillosis. We are studying Aspergillus wall formation in the tractable model system, A. nidulans. Previously we showed single-gene deletions of three sequential A. nidulans Galf biosynthesis proteins each caused similar hyphal morphogenesis defects and 500-fold reduced colony growth and sporulation. Here, we generated ugeA, ugmA and ugtA strains controlled by the alcA(p) or niiA(p) regulatable promoters. For repression and expression, alcA(p)-regulated strains were grown on complete medium with glucose or threonine, whereas niiA(p)-regulated strains were grown on minimal medium with ammonium or nitrate. Expression was assessed by qPCR and colony phenotype. The alcA(p) and niiA(p) strains produced similar effects: colonies resembling wild type for gene expression, and resembling deletion strains for gene repression. Galf immunolocalization using the L10 monoclonal antibody showed that ugmA deletion and repression phenotypes correlated with loss of hyphal wall Galf. None of the gene manipulations affected itraconazole sensitivity, as expected. Deletion of any of ugmA, ugeA, ugtA, their repression by alcA(p) or niiA(p), OR, ugmA overexpression by alcA(p), increased sensitivity to Caspofungin. Strains with alcA(p)-mediated overexpression of ugeA and ugtA had lower caspofungin sensitivity. Galf appears to play an important role in A. nidulans growth and vigor.

  15. [Examination of factors affecting efficacy and adverse effect, for the retrospective study of vancomycin hydrochloride (VCM)].

    PubMed

    Tanaka, M; Orii, T; Kobayashi, H; Hirono, S

    2001-08-01

    Vancomycin hydrochloride (VCM) is widely used for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. However, this drug can cause sever adverse reactions, such as red neck syndrome, nephrotoxicity and ototoxicity. Thus, therapeutic drug monitoring (TDM) was bringing into effect for well effectiveness and to prevent side effects. In Kanto Medical Center NTT EC, TDM of VCM has been brought into effect since 1994. The date were accumulated from 200 patients. In this study, the retrospective research was carried out based on 117 cases selected from the above accumulated data, and then several factors such as VCM inducing side effect, a therapeutic effect, and the forecast of pharmacokinetic parameter using laboratory data were examined. Consequently, the high blood concentration trough level, the high value after 1 to 2 hours infusion, and the extension of t1/2 were brought forward as a nephrotoxicity causing factor, and more over each laboratory data (BUN, Cr, GOT, GPT, gamma-GTP, T-BiL, ALP, LDH) was high before infusion of VCM in patients with renal dysfunction. High value T-Bil and lower value TP were brought forward in patients with hepatic dysfunction, and high eosinophils and high blood concentration were brought forward after 1 or 2 hours infusion. In relation to side effects, it was found that the outbreak rate of side effects is high in patients with a complication of hypertension or diabetes. The administration term was considered as a factor which influences the therapeutic effects. The unchanged effect was 10.9 +/- 7.9 days, the improved effect was 14.6 +/- 9.3 days, the remarkably improved effect was 17.7 +/- 14.1 days. As the administration term gets longer, the improvement rate was recognized to be an upward tendency. The difference in significant effects was recognized between unchanged and remarkably unchanged (p < 0.05) effects. As the forecast of pharmacokinetic parameter using the laboratory data, VCMt1/2 showed a

  16. Depressing Antidepressant: Fluoxetine Affects Serotonin Neurons Causing Adverse Reproductive Responses in Daphnia magna.

    PubMed

    Campos, Bruno; Rivetti, Claudia; Kress, Timm; Barata, Carlos; Dircksen, Heinrich

    2016-06-01

    Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. As endocrine disruptive contaminants in the environment, SSRIs affect reproduction in aquatic organisms. In the water flea Daphnia magna, SSRIs increase offspring production in a food ration-dependent manner. At limiting food conditions, females exposed to SSRIs produce more but smaller offspring, which is a maladaptive life-history strategy. We asked whether increased serotonin levels in newly identified serotonin-neurons in the Daphnia brain mediate these effects. We provide strong evidence that exogenous SSRI fluoxetine selectively increases serotonin-immunoreactivity in identified brain neurons under limiting food conditions thereby leading to maladaptive offspring production. Fluoxetine increases serotonin-immunoreactivity at low food conditions to similar maximal levels as observed under high food conditions and concomitantly enhances offspring production. Sublethal amounts of the neurotoxin 5,7-dihydroxytryptamine known to specifically ablate serotonin-neurons markedly decrease serotonin-immunoreactivity and offspring production, strongly supporting the effect to be serotonin-specific by reversing the reproductive phenotype attained under fluoxetine. Thus, SSRIs impair serotonin-regulation of reproductive investment in a planktonic key organism causing inappropriately increased reproduction with potentially severe ecological impact. PMID:27128505

  17. Combining S-cone and luminance signals adversely affects discrimination of objects within backgrounds

    PubMed Central

    Jennings, Ben J.; Tsattalios, Konstantinos; Chakravarthi, Ramakrishna; Martinovic, Jasna

    2016-01-01

    The visual system processes objects embedded in complex scenes that vary in both luminance and colour. In such scenes, colour contributes to the segmentation of objects from backgrounds, but does it also affect perceptual organisation of object contours which are already defined by luminance signals, or are these processes unaffected by colour’s presence? We investigated if luminance and chromatic signals comparably sustain processing of objects embedded in backgrounds, by varying contrast along the luminance dimension and along the two cone-opponent colour directions. In the first experiment thresholds for object/non-object discrimination of Gaborised shapes were obtained in the presence and absence of background clutter. Contrast of the component Gabors was modulated along single colour/luminance dimensions or co-modulated along multiple dimensions simultaneously. Background clutter elevated discrimination thresholds only for combined S-(L + M) and L + M signals. The second experiment replicated and extended this finding by demonstrating that the effect was dependent on the presence of relatively high S-(L + M) contrast. These results indicate that S-(L + M) signals impair spatial vision when combined with luminance. Since S-(L + M) signals are characterised by relatively large receptive fields, this is likely to be due to an increase in the size of the integration field over which contour-defining information is summed. PMID:26856308

  18. Nutrient supplementation may adversely affect maternal oral health--a randomised controlled trial in rural Malawi.

    PubMed

    Harjunmaa, Ulla; Järnstedt, Jorma; Dewey, Kathryn G; Ashorn, Ulla; Maleta, Kenneth; Vosti, Stephen A; Ashorn, Per

    2016-01-01

    Nutritional supplementation during pregnancy is increasingly recommended especially in low-resource settings, but its oral health impacts have not been studied. Our aim was to examine whether supplementation with multiple micronutrients (MMN) or small-quantity lipid-based nutrient supplements affects dental caries development or periodontal health in a rural Malawian population. The study was embedded in a controlled iLiNS-DYAD trial that enrolled 1391 pregnant women <20 gestation weeks. Women were provided with one daily iron-folic acid capsule (IFA), one capsule with 18 micronutrients (MMN) or one sachet of lipid-based nutrient supplements (LNS) containing protein, carbohydrates, essential fatty acids and 21 micronutrients. Oral examination of 1024 participants was conducted and panoramic X-ray taken within 6 weeks after delivery. The supplement groups were similar at baseline in average socio-economic, nutritional and health status. At the end of the intervention, the prevalence of caries was 56.7%, 69.1% and 63.3% (P = 0.004), and periodontitis 34.9%, 29.8% and 31.2% (P = 0.338) in the IFA, MMN and LNS groups, respectively. Compared with the IFA group, women in the MMN group had 0.60 (0.18-1.02) and in the LNS group 0.59 (0.17-1.01) higher mean number of caries lesions. In the absence of baseline oral health data, firm conclusions on causality cannot be drawn. However, although not confirmatory, the findings are consistent with a possibility that provision of MMN or LNS may have increased the caries incidence in this target population. Because of the potential public health impacts, further research on the association between gestational nutrient interventions and oral health in low-income settings is needed.

  19. Food quantity affects the sensitivity of Daphnia to road salt.

    PubMed

    Brown, Arran H; Yan, Norman D

    2015-04-01

    Road deicing operations have raised chloride (Cl) levels in many temperate lakes in Europe and North America. These lakes vary widely in trophic status, but to date, no one has quantified the interaction between food quantity and road salt toxicity. We examined the effects of food quantity (particulate algal C concentration (C)) on the chronic toxicity of Cl to Daphnia in soft-water bioassays. There was a strong positive linear relationship (r(2) = 0.92 for NaCl and r(2) = 0.96 for CaCl2) between food quantity and Cl LC50. As food quantity increased from 0.2 to 1.0 mg C/L (levels characteristic of oligotrophic to eutrophic lakes, respectively), the chronic Cl LC50 increased from 55.7 to 284.8 mg Cl/L. Salt type (NaCl or CaCl2) did not affect the Cl LC50, Daphnia life history parameters, or the intrinsic rate of population increase (r). The life history parameter most sensitive to Cl was neonate production. Cl did not inhibit egg production, nor was the maternal lipid investment in eggs changed, but egg viability and the subsequent release of live neonates decreased as Cl levels increased and food decreased. Our results suggest the trophic status of lakes should be considered when assessing ecological threat from Cl. PMID:25751457

  20. Genes Affecting Sensitivity to Serotonin in Caenorhabditis Elegans

    PubMed Central

    Schafer, W. R.; Sanchez, B. M.; Kenyon, C. J.

    1996-01-01

    Regulating the response of a postsynaptic cell to neurotransmitter is an important mechanism for controlling synaptic strength, a process critical to learning. We have begun to define and characterize genes that may control sensitivity to the neurotransmitter serotonin in the nematode Caenorhabditis elegans by identifying serotonin-hypersensitive mutants. We reported previously that mutations in the gene unc-2, which encodes a putative calcium channel subunit, result in hypersensitivity to serotonin. Here we report that mutants defective in the unc-36 gene, which encodes a homologue of a calcium channel auxiliary subunit, are also serotonin-hypersensitive. Moreover, the unc-36 gene appears to be required in the same cells as unc-2 for control of the same behaviors. Mutations in several other genes, including unc-8, unc-10, unc-20, unc-35, unc-75, unc-77, and snt-1 also result in hypersensitivity to serotonin. Several of these mutations have previously been shown to confer resistance to acetylcholinesterase inhibitors, suggesting that they may affect acetylcholine release. Moreover, we found that mutations that decrease acetylcholine synthesis cause defective egg-laying and serotonin hypersensitivity. Thus, acetylcholine appears to negatively regulate the response to serotonin and may participate in the process of serotonin desensitization. PMID:8807295

  1. Variations in Maternal 5-HTTLPR Affect Observed Sensitive Parenting

    ERIC Educational Resources Information Center

    Cents, Rolieke A. M.; Kok, Rianne; Tiemeier, Henning; Lucassen, Nicole; Székely, Eszter; Bakermans-Kranenburg, Marian J.; Hofman, Albert; Jaddoe, Vincent W. V.; IJzendoorn, Marinus H.; Verhulst, Frank C.; Lambregtse-van den Berg, Mijke P.

    2014-01-01

    Background: Little is known about the genetic determinants of sensitive parenting. Two earlier studies examined the effect of the serotonin transporter polymorphism (5-HTTLPR) on sensitive parenting, but reported opposite results. In a large cohort we further examined whether 5-HTTLPR is a predictor of observed maternal sensitivity and whether…

  2. Calmodulin Affects Sensitization of Drosophila melanogaster Odorant Receptors

    PubMed Central

    Mukunda, Latha; Miazzi, Fabio; Sargsyan, Vardanush; Hansson, Bill S.; Wicher, Dieter

    2016-01-01

    Flying insects have developed a remarkably sensitive olfactory system to detect faint and turbulent odor traces. This ability is linked to the olfactory receptors class of odorant receptors (ORs), occurring exclusively in winged insects. ORs form heteromeric complexes of an odorant specific receptor protein (OrX) and a highly conserved co-receptor protein (Orco). The ORs form ligand gated ion channels that are tuned by intracellular signaling systems. Repetitive subthreshold odor stimulation of olfactory sensory neurons sensitizes insect ORs. This OR sensitization process requires Orco activity. In the present study we first asked whether OR sensitization can be monitored with heterologously expressed OR proteins. Using electrophysiological and calcium imaging methods we demonstrate that D. melanogaster OR proteins expressed in CHO cells show sensitization upon repeated weak stimulation. This was found for OR channels formed by Orco as well as by Or22a or Or56a and Orco. Moreover, we show that inhibition of calmodulin (CaM) action on OR proteins, expressed in CHO cells, abolishes any sensitization. Finally, we investigated the sensitization phenomenon using an ex vivo preparation of olfactory sensory neurons (OSNs) expressing Or22a inside the fly's antenna. Using calcium imaging, we observed sensitization in the dendrites as well as in the soma. Inhibition of calmodulin with W7 disrupted the sensitization within the outer dendritic shaft, whereas the sensitization remained in the other OSN compartments. Taken together, our results suggest that CaM action is involved in sensitizing the OR complex and that this mechanisms accounts for the sensitization in the outer dendrites, whereas further mechanisms contribute to the sensitization observed in the other OSN compartments. The use of heterologously expressed OR proteins appears to be suitable for further investigations on the mechanistic basis of OR sensitization, while investigations on native neurons are required

  3. The cultivation of Bt corn producing Cry1Ac toxins does not adversely affect non-target arthropods.

    PubMed

    Guo, Yanyan; Feng, Yanjie; Ge, Yang; Tetreau, Guillaume; Chen, Xiaowen; Dong, Xuehui; Shi, Wangpeng

    2014-01-01

    Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon's diversity index, Pielou's evenness index and Simpson's diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The "sampling dates" had a significant effect on these indices, but no clear tendencies related to "Bt corn" or "sampling dates X corn variety" interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs.

  4. Importance and sensitivity of parameters affecting the Zion Seismic Risk

    SciTech Connect

    George, L.L.; O'Connell, W.J.

    1985-06-01

    This report presents the results of a study on the importance and sensitivity of structures, systems, equipment, components and design parameters used in the Zion Seismic Risk Calculations. This study is part of the Seismic Safety Margins Research Program (SSMRP) supported by the NRC Office of Nuclear Regulatory Research. The objective of this study is to provide the NRC with results on the importance and sensitivity of parameters used to evaluate seismic risk. These results can assist the NRC in making decisions dealing with the allocation of research resources on seismic issues. This study uses marginal analysis in addition to importance and sensitivity analysis to identify subject areas (input parameter areas) for improvements that reduce risk, estimate how much the improvement dfforts reduce risk, and rank the subject areas for improvements. Importance analysis identifies the systems, components, and parameters that are important to risk. Sensitivity analysis estimates the change in risk per unit improvement. Marginal analysis indicates the reduction in risk or uncertainty for improvement effort made in each subject area. The results described in this study were generated using the SEISIM (Systematic Evaluation of Important Safety Improvement Measures) and CHAIN computer codes. Part 1 of the SEISIM computer code generated the failure probabilities and risk values. Part 2 of SEISIM, along with the CHAIN computer code, generated the importance and sensitivity measures.

  5. Sensitive periods in affective development: nonlinear maturation of fear learning.

    PubMed

    Hartley, Catherine A; Lee, Francis S

    2015-01-01

    At specific maturational stages, neural circuits enter sensitive periods of heightened plasticity, during which the development of both brain and behavior are highly receptive to particular experiential information. A relatively advanced understanding of the regulatory mechanisms governing the initiation, closure, and reinstatement of sensitive period plasticity has emerged from extensive research examining the development of the visual system. In this article, we discuss a large body of work characterizing the pronounced nonlinear changes in fear learning and extinction that occur from childhood through adulthood, and their underlying neural substrates. We draw upon the model of sensitive period regulation within the visual system, and present burgeoning evidence suggesting that parallel mechanisms may regulate the qualitative changes in fear learning across development.

  6. The cultivation of Bt corn producing Cry1Ac toxins does not adversely affect non-target arthropods.

    PubMed

    Guo, Yanyan; Feng, Yanjie; Ge, Yang; Tetreau, Guillaume; Chen, Xiaowen; Dong, Xuehui; Shi, Wangpeng

    2014-01-01

    Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon's diversity index, Pielou's evenness index and Simpson's diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The "sampling dates" had a significant effect on these indices, but no clear tendencies related to "Bt corn" or "sampling dates X corn variety" interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs. PMID:25437213

  7. The Cultivation of Bt Corn Producing Cry1Ac Toxins Does Not Adversely Affect Non-Target Arthropods

    PubMed Central

    Guo, Yanyan; Feng, Yanjie; Ge, Yang; Tetreau, Guillaume; Chen, Xiaowen; Dong, Xuehui; Shi, Wangpeng

    2014-01-01

    Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon's diversity index, Pielou's evenness index and Simpson's diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The “sampling dates” had a significant effect on these indices, but no clear tendencies related to “Bt corn” or “sampling dates X corn variety” interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs. PMID:25437213

  8. FACTORS AFFECTING SENSITIVITY OF CHEMICAL AND ECOLOGICAL RESPONSES OF MARINE EMBAYMEMTS TO NITROGEN LOADING

    EPA Science Inventory

    This paper summarizes an ongoing examination of the primary factors that affect sensitivity of marine embayment responses to nitrogen loading. Included is a discussion of two methods for using these factors: classification of embayments into discrete sensitivity classes and norma...

  9. Infant Sensitivity to Distributional Information Can Affect Phonetic Discrimination.

    ERIC Educational Resources Information Center

    Maye, Jessica; Werker, Janet F.; Gerken, LouAnn

    2002-01-01

    Familiarized 6- and 8-month-olds with speech sounds from a phonetic continuum, exhibiting a bimodal or unimodal frequency distribution. Found that only infants in the bimodal condition discriminated tokens from the endpoints of the continuum. Results demonstrate that infants are sensitive to the statistical distribution of speech sounds in the…

  10. Does ecohydrological connectivity affect sensitivity to environmental change?

    EPA Science Inventory

    Our goal is to understand the influences of complex terrain on the sensitivity of carbon and water cycle processes to environmental drivers at different scales. Gravity-driven flowpaths of air and water transport material and energy across and through landscapes, creating connec...

  11. A Computational Study on the Effects of Dynamic Roughness Application to Separated Transitional Flows Affected by Adverse Pressure Gradient

    NASA Astrophysics Data System (ADS)

    Campitelli, Gennaro

    The study of transitional flows is considered crucial for many practical engineering applications. In fact, a comprehensive understanding of the laminar-turbulent transition phenomenon often helps to improve the overall performance of apparatuses such as airfoils, wind turbines, hulls and turbomachinery blades. In addition to understanding and prediction of transitional flows, active research continues in the area of boundary layer control, which includes control of phenomena such as flow separation and transition. For instance, optimum geometrical shaping may be followed by the adoption on the wall-surface of riblets to adjust pressure gradient and reduce drag. Further "flow control" may also be acquired by introducing active devices able to modify the flow field in order to accomplish a desired aerodynamic task. Such flow manipulation is often achieved by using time-dependent forcing mechanisms which promote natural instabilities amplifying the control effectiveness. Localized energy inputs such as Lorentz-force actuator, piezoelectric flaps and synthetic jets all produce a consistent boundary layer mixing enhancement with lift increase and drag abatement. The current numerical study attempts to demonstrate the efficacy of dynamic roughness (DR) on altering separated-reattached transitional flows under adverse pressure gradient. It has already been proven how DR, acting on the boundary sublayer perturbation, is able to suppress (partially or completely) the typical leading edge separation for an airfoil at different angles of attack. This makes DR particularly suitable for separated flow control applications where the shear layer reattaches presenting the characteristic laminar separation bubble. A numerical sensitivity study has been conducted with an efficient orthogonal design taking into account four different control parameters on three levels (actuation frequency, humps height, rows displacement, synchronization) to provide an optimum DR setup which limits

  12. Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study.

    PubMed

    Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R; Zhao, Xiaoyi; Ruan, Yanping; Yan, Jianhua; Mukherjee, Bhramar; Rao, Xiaoquan; Duan, Fengkui; Sun, Lixian; Liang, Ruijuan; Lian, Hui; Zhang, Shuyang; Fang, Quan; Gu, Dongfeng; Sun, Qinghua; Fan, Zhongjie; Rajagopalan, Sanjay

    2016-01-01

    Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m(3) and 0.2 to 24.5 µg/m(3), respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3-3.7) to 2.7 (0.6-4.8) mm Hg per SD increase (67.2 µg/m(3)), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mm Hg per SD increase (3.6 µg/m(3)). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01-0.36] and 0.22 [0.04-0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02-0.34] and 0.22 [0.08-0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today. PMID:26573709

  13. Increased Fracture Collapse after Intertrochanteric Fractures Treated by the Dynamic Hip Screw Adversely Affects Walking Ability but Not Survival

    PubMed Central

    Fang, Christian; Gudushauri, Paata; Wong, Tak-Man; Lau, Tak-Wing; Pun, Terence; Leung, Frankie

    2016-01-01

    In osteoporotic hip fractures, fracture collapse is deliberately allowed by commonly used implants to improve dynamic contact and healing. The muscle lever arm is, however, compromised by shortening. We evaluated a cohort of 361 patients with AO/OTA 31.A1 or 31.A2 intertrochanteric fracture treated by the dynamic hip screw (DHS) who had a minimal follow-up of 3 months and an average follow-up of 14.6 months and long term survival data. The amount of fracture collapse and shortening due to sliding of the DHS was determined at the latest follow-up and graded as minimal (<1 cm), moderate (1-2 cm), or severe (>2 cm). With increased severity of collapse, more patients were unable to maintain their premorbid walking function (minimal collapse = 34.2%, moderate = 33.3%, severe = 62.8%, and p = 0.028). Based on ordinal regression of risk factors, increased fracture collapse was significantly and independently related to increasing age (p = 0.037), female sex (p = 0.024), A2 fracture class (p = 0.010), increased operative duration (p = 0.011), poor reduction quality (p = 0.000), and suboptimal tip-apex distance of >25 mm (p = 0.050). Patients who had better outcome in terms of walking function were independently predicted by younger age (p = 0.036), higher MMSE marks (p = 0.000), higher MBI marks (p = 0.010), better premorbid walking status (p = 0.000), less fracture collapse (p = 0.011), and optimal lag screw position in centre-centre or centre-inferior position (p = 0.020). According to Kaplan-Meier analysis, fracture collapse had no association with mortality from 2.4 to 7.6 years after surgery. In conclusion, increased fracture collapse after fixation of geriatric intertrochanteric fractures adversely affected walking but not survival. PMID:26955637

  14. Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study.

    PubMed

    Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R; Zhao, Xiaoyi; Ruan, Yanping; Yan, Jianhua; Mukherjee, Bhramar; Rao, Xiaoquan; Duan, Fengkui; Sun, Lixian; Liang, Ruijuan; Lian, Hui; Zhang, Shuyang; Fang, Quan; Gu, Dongfeng; Sun, Qinghua; Fan, Zhongjie; Rajagopalan, Sanjay

    2016-01-01

    Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m(3) and 0.2 to 24.5 µg/m(3), respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3-3.7) to 2.7 (0.6-4.8) mm Hg per SD increase (67.2 µg/m(3)), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mm Hg per SD increase (3.6 µg/m(3)). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01-0.36] and 0.22 [0.04-0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02-0.34] and 0.22 [0.08-0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

  15. Sucrose Sensitivity of Honey Bees Is Differently Affected by Dietary Protein and a Neonicotinoid Pesticide.

    PubMed

    Démares, Fabien J; Crous, Kendall L; Pirk, Christian W W; Nicolson, Susan W; Human, Hannelie

    2016-01-01

    Over a decade, declines in honey bee colonies have raised worldwide concerns. Several potentially contributing factors have been investigated, e.g. parasites, diseases, and pesticides. Neonicotinoid pesticides have received much attention due to their intensive use in crop protection, and their adverse effects on many levels of honey bee physiology led the European Union to ban these compounds. Due to their neuronal target, a receptor expressed throughout the insect nervous system, studies have focused mainly on neuroscience and behaviour. Through the Geometric Framework of nutrition, we investigated effects of the neonicotinoid thiamethoxam on survival, food consumption and sucrose sensitivity of honey bees (Apis mellifera). Thiamethoxam did not affect protein and carbohydrate intake, but decreased responses to high concentrations of sucrose. Interestingly, when bees ate fixed unbalanced diets, dietary protein facilitated better sucrose detection. Both thiamethoxam and dietary protein influenced survival. These findings suggest that, in the presence of a pesticide and unbalanced food, honey bee health may be severely challenged. Consequences for foraging efficiency and colony activity, cornerstones of honey bee health, are also discussed. PMID:27272274

  16. Sucrose Sensitivity of Honey Bees Is Differently Affected by Dietary Protein and a Neonicotinoid Pesticide.

    PubMed

    Démares, Fabien J; Crous, Kendall L; Pirk, Christian W W; Nicolson, Susan W; Human, Hannelie

    2016-01-01

    Over a decade, declines in honey bee colonies have raised worldwide concerns. Several potentially contributing factors have been investigated, e.g. parasites, diseases, and pesticides. Neonicotinoid pesticides have received much attention due to their intensive use in crop protection, and their adverse effects on many levels of honey bee physiology led the European Union to ban these compounds. Due to their neuronal target, a receptor expressed throughout the insect nervous system, studies have focused mainly on neuroscience and behaviour. Through the Geometric Framework of nutrition, we investigated effects of the neonicotinoid thiamethoxam on survival, food consumption and sucrose sensitivity of honey bees (Apis mellifera). Thiamethoxam did not affect protein and carbohydrate intake, but decreased responses to high concentrations of sucrose. Interestingly, when bees ate fixed unbalanced diets, dietary protein facilitated better sucrose detection. Both thiamethoxam and dietary protein influenced survival. These findings suggest that, in the presence of a pesticide and unbalanced food, honey bee health may be severely challenged. Consequences for foraging efficiency and colony activity, cornerstones of honey bee health, are also discussed.

  17. Sucrose Sensitivity of Honey Bees Is Differently Affected by Dietary Protein and a Neonicotinoid Pesticide

    PubMed Central

    Démares, Fabien J.; Crous, Kendall L.; Pirk, Christian W. W.; Nicolson, Susan W.; Human, Hannelie

    2016-01-01

    Over a decade, declines in honey bee colonies have raised worldwide concerns. Several potentially contributing factors have been investigated, e.g. parasites, diseases, and pesticides. Neonicotinoid pesticides have received much attention due to their intensive use in crop protection, and their adverse effects on many levels of honey bee physiology led the European Union to ban these compounds. Due to their neuronal target, a receptor expressed throughout the insect nervous system, studies have focused mainly on neuroscience and behaviour. Through the Geometric Framework of nutrition, we investigated effects of the neonicotinoid thiamethoxam on survival, food consumption and sucrose sensitivity of honey bees (Apis mellifera). Thiamethoxam did not affect protein and carbohydrate intake, but decreased responses to high concentrations of sucrose. Interestingly, when bees ate fixed unbalanced diets, dietary protein facilitated better sucrose detection. Both thiamethoxam and dietary protein influenced survival. These findings suggest that, in the presence of a pesticide and unbalanced food, honey bee health may be severely challenged. Consequences for foraging efficiency and colony activity, cornerstones of honey bee health, are also discussed. PMID:27272274

  18. Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena.

    PubMed

    Post, Robert M

    2007-01-01

    We use the non-homologous model of sensitization and kindling to help conceptualize processes occurring in the longitudinal course of bipolar disorder. The models help focus on the phenomena of episode recurrence, regression, and cycle acceleration occurring without medication and during treatment, when these progressive processes can re-emerge during tolerance development. The preclinical data suggest that it is the ratio of pathological versus adaptive factors mediated by changes in gene expression that mediate episode recurrence or suppression. During tolerance development, there may be selective loss of some episode-induced adaptive factors that may be re-engendered during a period off that medication. The models reveal long-term molecular changes induced by recurrent stresses, episodes of illness, and substances of abuse that can accumulate and lead to progressive increases in vulnerability to episode recurrence. The clinical and preclinical data converge in emphasizing the importance of prevention and early and sustained prophylaxis. New data also implicate brain-derived neurotrophic factor (BDNF) in genetic and environmental illness vulnerability and progression, as well as in the mechanisms of action of the mood stabilizers and antidepressants. Therapeutic agents may thus not only prevent recurrent affective episodes and their adverse consequences on the brain, behavior, and quality of life, but they may also be able to ameliorate the effects of stressors, and reverse or prevent some of the basic pathological brain mechanisms underlying illness progression.

  19. Parameters affecting the sensitivities of dideoxy fingerprinting and SSCP.

    PubMed

    Liu, Q; Sommer, S S

    1994-10-01

    The goals of the present experiments are (1) to improve dideoxy fingerprinting (ddF) and (2) to utilize ddF as a tool to evaluate the relative merits of different conditions for single-strand conformation polymorphism (SSCP). ddF is performed by electrophoresing one dideoxy termination reaction through a nondenaturing gel. The ddF pattern can be divided into a "dideoxy component" and an "SSCP component". If dideoxy CTP (ddCTP) is utilized for the termination reaction of ddF, the dideoxy component is abnormal when an extra segment is produced by a sequence change that creates an extra C or when a segment is eliminated by a change of C to another base. All subsequent segments produced by the termination reaction constitute the SSCP component that contains the mutation in a nested series of ddCTP termination products. The SSCP component is informative if abnormal mobility is detected in one or more of the segments. Herein, we utilize 84 different single-base changes in the human factor IX gene to examine the effects of gel matrix, temperature, and different primers on the sensitivity of ddF. The effects of glycerol and cross-linker ratio were examined on fewer mutations. The following conclusions emerge: 1. The sensitivity of the dideoxy component is invariant, but the sensitivity of the SSCP component can vary greatly with gel matrix, temperature, segment size, and sequence context. 2. For a given segment containing a mutation, it is likely that a mobility shift will be seen under some conditions but not under other conditions. By examining the mobility of the SSCP component in > 2200 segments, it was found that some conditions are statistically more likely to result in altered mobility, thereby increasing the average sensitivity of mutation detection by ddF or conventional SSCP. 3. GeneAmp and MDE gels are superior to polyacrylamide gels and electrophoresis at 8 degrees C is superior to electrophoresis at 23 degrees C. GeneAmp at 8 degrees C provided the highest

  20. Endocrine disrupters and human health: could oestrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women?

    PubMed

    Harvey, Philip W; Darbre, Philippa

    2004-01-01

    In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected in human breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of: data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, because exposure to oestrogenic chemicals through application

  1. Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study.

    PubMed

    Saridjan, Nathalie S; Huizink, Anja C; Koetsier, Jitske A; Jaddoe, Vincent W; Mackenbach, Johan P; Hofman, Albert; Kirschbaum, Clemens; Verhulst, Frank C; Tiemeier, Henning

    2010-02-01

    Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic-pituitary-adrenal (HPA) axis early in life. In 366 infants aged 12-20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires. We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis. PMID:20006614

  2. Mitochondrial haplotype divergences affect specific temperature sensitivity of mitochondrial respiration.

    PubMed

    Pichaud, Nicolas; Ballard, J William O; Tanguay, Robert M; Blier, Pierre U

    2013-02-01

    The aim of this study was to investigate the effect of temperature changes on the functional properties of mitochondria from two sets of D. simulans fly lines harboring the siII and siIII haplotypes in a common nuclear genetic background. We studied four introgressed isofemale lines possessing the mtDNA of siII and the nuclear background of siIII (siII-introgressed) and four lines possessing siIII mitochondria with its native nuclear genome (siIII-controls). We assessed the catalytic capacities of electron transport system (ETS) at four different temperatures (12, 18, 24 and 28 ºC). The impact of temperature on the pyruvate dehydrogenase (PDH) activity, the mitochondrial respiration (coupled and uncoupled respiration), cytochrome c oxidase activity, as well as the excess capacity of complex IV (COX) were evaluated in these two sets of flies. Our results showed that the temperature coefficient values (Q(10)) measured for mitochondrial respiration in the lower range of temperatures (12 to 18 ºC) showed a 2 to 3 fold increase in siII-introgressed when compared to siIII-controls. This result shows that the impact of temperature on mitochondrial function is different between the two mitotypes studied. The Q(10) results seem to be linked to the apparent COX excess capacity of 193% for siIII-controls that is inexistent for siII-introgressed at 12 ºC. One explanation for these results is that the mitochondria can compensate for the disruption of mito-nuclear interactions at 24 ºC but not at lower temperatures. An alternate explanation would be that siII haplotype confer divergent kinetic properties to the ETS that translate to different temperature sensitivities.

  3. Mitochondrial haplotype divergences affect specific temperature sensitivity of mitochondrial respiration.

    PubMed

    Pichaud, Nicolas; Ballard, J William O; Tanguay, Robert M; Blier, Pierre U

    2013-02-01

    The aim of this study was to investigate the effect of temperature changes on the functional properties of mitochondria from two sets of D. simulans fly lines harboring the siII and siIII haplotypes in a common nuclear genetic background. We studied four introgressed isofemale lines possessing the mtDNA of siII and the nuclear background of siIII (siII-introgressed) and four lines possessing siIII mitochondria with its native nuclear genome (siIII-controls). We assessed the catalytic capacities of electron transport system (ETS) at four different temperatures (12, 18, 24 and 28 ºC). The impact of temperature on the pyruvate dehydrogenase (PDH) activity, the mitochondrial respiration (coupled and uncoupled respiration), cytochrome c oxidase activity, as well as the excess capacity of complex IV (COX) were evaluated in these two sets of flies. Our results showed that the temperature coefficient values (Q(10)) measured for mitochondrial respiration in the lower range of temperatures (12 to 18 ºC) showed a 2 to 3 fold increase in siII-introgressed when compared to siIII-controls. This result shows that the impact of temperature on mitochondrial function is different between the two mitotypes studied. The Q(10) results seem to be linked to the apparent COX excess capacity of 193% for siIII-controls that is inexistent for siII-introgressed at 12 ºC. One explanation for these results is that the mitochondria can compensate for the disruption of mito-nuclear interactions at 24 ºC but not at lower temperatures. An alternate explanation would be that siII haplotype confer divergent kinetic properties to the ETS that translate to different temperature sensitivities. PMID:23054075

  4. Benefits of adversity?! How life history affects the behavioral profile of mice varying in serotonin transporter genotype

    PubMed Central

    Bodden, Carina; Richter, S. Helene; Schreiber, Rebecca S.; Kloke, Vanessa; Gerß, Joachim; Palme, Rupert; Lesch, Klaus-Peter; Lewejohann, Lars; Kaiser, Sylvia; Sachser, Norbert

    2015-01-01

    Behavioral profiles are influenced by both positive and negative experiences as well as the genetic disposition. Traditionally, accumulating adversity over lifetime is considered to predict increased anxiety-like behavior (“allostatic load”). The alternative “mismatch hypothesis” suggests increased levels of anxiety if the early environment differs from the later-life environment. Thus, there is a need for a whole-life history approach to gain a deeper understanding of how behavioral profiles are shaped. The aim of this study was to elucidate the effects of life history on the behavioral profile of mice varying in serotonin transporter (5-HTT) genotype, an established mouse model of increased anxiety-like behavior. For this purpose, mice grew up under either adverse or beneficial conditions during early phases of life. In adulthood, they were further subdivided so as to face a situation that either matched or mismatched the condition experienced so far, resulting in four different life histories. Subsequently, mice were tested for their anxiety-like and exploratory behavior. The main results were: (1) Life history profoundly modulated the behavioral profile. Surprisingly, mice that experienced early beneficial and later escapable adverse conditions showed less anxiety-like and more exploratory behavior compared to mice of other life histories. (2) Genotype significantly influenced the behavioral profile, with homozygous 5-HTT knockout mice displaying highest levels of anxiety-like and lowest levels of exploratory behavior. Our findings concerning life history indicate that the absence of adversity does not necessarily cause lower levels of anxiety than accumulating adversity. Rather, some adversity may be beneficial, particularly when following positive events. Altogether, we conclude that for an understanding of behavioral profiles, it is not sufficient to look at experiences during single phases of life, but the whole life history has to be considered

  5. Adverse Social Experiences in Adolescent Rats Result in Enduring Effects on Social Competence, Pain Sensitivity and Endocannabinoid Signaling

    PubMed Central

    Schneider, Peggy; Bindila, Laura; Schmahl, Christian; Bohus, Martin; Meyer-Lindenberg, Andreas; Lutz, Beat; Spanagel, Rainer; Schneider, Miriam

    2016-01-01

    Social affiliation is essential for many species and gains significant importance during adolescence. Disturbances in social affiliation, in particular social rejection experiences during adolescence, affect an individual’s well-being and are involved in the emergence of psychiatric disorders. The underlying mechanisms are still unknown, partly because of a lack of valid animal models. By using a novel animal model for social peer-rejection, which compromises adolescent rats in their ability to appropriately engage in playful activities, here we report on persistent impairments in social behavior and dysregulations in the endocannabinoid (eCB) system. From postnatal day (pd) 21 to pd 50 adolescent female Wistar rats were either reared with same-strain partners (control) or within a group of Fischer 344 rats (inadequate social rearing, ISR), previously shown to serve as inadequate play partners for the Wistar strain. Adult ISR animals showed pronounced deficits in social interaction, social memory, processing of socially transmitted information, and decreased pain sensitivity. Molecular analysis revealed increased CB1 receptor (CB1R) protein levels and CP55, 940 stimulated [35S]GTPγS binding activity specifically in the amygdala and thalamus in previously peer-rejected rats. Along with these changes, increased levels of the eCB anandamide (AEA) and a corresponding decrease of its degrading enzyme fatty acid amide hydrolase (FAAH) were seen in the amygdala. Our data indicate lasting consequences in social behavior and pain sensitivity following peer-rejection in adolescent female rats. These behavioral impairments are accompanied by persistent alterations in CB1R signaling. Finally, we provide a novel translational approach to characterize neurobiological processes underlying social peer-rejection in adolescence. PMID:27812328

  6. Biological Sensitivity to Context: The Interactive Effects of Stress Reactivity and Family Adversity on Socioemotional Behavior and School Readiness

    ERIC Educational Resources Information Center

    Obradovic, Jelena; Bush, Nicole R.; Stamperdahl, Juliet; Adler, Nancy E.; Boyce, W. Thomas

    2010-01-01

    This study examined the direct and interactive effects of stress reactivity and family adversity on socioemotional and cognitive development in three hundred and thirty-eight 5- to 6-year-old children. Neurobiological stress reactivity was measured as respiratory sinus arrhythmia and salivary cortisol responses to social, cognitive, sensory, and…

  7. CT and MR imaging findings of systemic complications occurring during pregnancy and puerperal period, adversely affected by natural changes

    PubMed Central

    Himoto, Yuki; Kido, Aki; Moribata, Yusaku; Yamaoka, Toshihide; Okumura, Ryosuke; Togashi, Kaori

    2015-01-01

    Dynamic physiological and anatomical changes for delivery may adversely induce various specific non-obstetric complications during pregnancy and puerperal period. These complications can be fatal to both the mother and the fetus, thus a precise and early diagnosis ensued by an early treatment is essential. Along with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) have assumed an increasing role in the diagnosis. This article aims to discuss the pathophysiology of these complications, the indications for CT and MRI, and the imaging findings. PMID:26937442

  8. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    PubMed Central

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. PMID:27536078

  9. Affective modulation of the startle reflex and the Reinforcement Sensitivity Theory of personality: The role of sensitivity to reward.

    PubMed

    Aluja, Anton; Blanch, Angel; Blanco, Eduardo; Balada, Ferran

    2015-01-01

    This study evaluated differences in the amplitude of startle reflex and Sensitivity to Reward (SR) and Sensitivity to Punishment (SP) personality variables of the Reinforcement Sensitivity Theory (RST). We hypothesized that subjects with higher scores in SR would obtain a higher startle reflex when exposed to pleasant pictures than lower scores, while higher scores in SP would obtain a higher startle reflex when exposed to unpleasant pictures than subjects with lower scores in this dimension. The sample consisted of 112 healthy female undergraduate psychology students. Personality was assessed using the short version of the Sensitivity to Punishment and Sensitivity Reward Questionnaire (SPSRQ). Laboratory anxiety was controlled by the State Anxiety Inventory. The startle blink reflex was recorded electromyographically (EMG) from the right orbicularis oculi muscle as a response to the International Affective Picture System (IAPS) pleasant, neutral and unpleasant pictures. Subjects higher in SR obtained a significant higher startle reflex response in pleasant pictures than lower scorers (48.48 vs 46.28, p<0.012). Subjects with higher scores in SP showed a light tendency of higher startle responses in unpleasant pictures in a non-parametric local regression graphical analysis (LOESS). The findings shed light on the relationships among the impulsive-disinhibited personality, including sensitivity to reward and emotions evoked through pictures of emotional content.

  10. Affective modulation of the startle reflex and the Reinforcement Sensitivity Theory of personality: The role of sensitivity to reward.

    PubMed

    Aluja, Anton; Blanch, Angel; Blanco, Eduardo; Balada, Ferran

    2015-01-01

    This study evaluated differences in the amplitude of startle reflex and Sensitivity to Reward (SR) and Sensitivity to Punishment (SP) personality variables of the Reinforcement Sensitivity Theory (RST). We hypothesized that subjects with higher scores in SR would obtain a higher startle reflex when exposed to pleasant pictures than lower scores, while higher scores in SP would obtain a higher startle reflex when exposed to unpleasant pictures than subjects with lower scores in this dimension. The sample consisted of 112 healthy female undergraduate psychology students. Personality was assessed using the short version of the Sensitivity to Punishment and Sensitivity Reward Questionnaire (SPSRQ). Laboratory anxiety was controlled by the State Anxiety Inventory. The startle blink reflex was recorded electromyographically (EMG) from the right orbicularis oculi muscle as a response to the International Affective Picture System (IAPS) pleasant, neutral and unpleasant pictures. Subjects higher in SR obtained a significant higher startle reflex response in pleasant pictures than lower scorers (48.48 vs 46.28, p<0.012). Subjects with higher scores in SP showed a light tendency of higher startle responses in unpleasant pictures in a non-parametric local regression graphical analysis (LOESS). The findings shed light on the relationships among the impulsive-disinhibited personality, including sensitivity to reward and emotions evoked through pictures of emotional content. PMID:25447471

  11. Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

    PubMed Central

    George, Anish; Bhatia, Raghav T.; Buchanan, Gill L.; Whiteside, Anne; Moisey, Robert S.; Beer, Stephen F.; Chattopadhyay, Sudipta; Sathyapalan, Thozhukat; John, Joseph

    2015-01-01

    Objective To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI). Research Design and Methods Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE. Results Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points. Conclusion Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention. PMID:26571120

  12. The Myeloid U937 Skin Sensitization Test (U-SENS) addresses the activation of dendritic cell event in the adverse outcome pathway for skin sensitization.

    PubMed

    Piroird, Cécile; Ovigne, Jean-Marc; Rousset, Françoise; Martinozzi-Teissier, Silvia; Gomes, Charles; Cotovio, José; Alépée, Nathalie

    2015-08-01

    The U-SENS™ assay, formerly known as MUSST (Myeloid U937 Skin Sensitization Test), is an in vitro method to assess skin sensitization. Dendritic cell activation following exposure to sensitizers was modelled in the U937 human myeloid cell line by measuring the induction of the expression of CD86 by flow cytometry. The predictive performance of U-SENS™ was assessed via a comprehensive comparison analysis with the available human and LLNA data of 175 substances. U-SENS™ showed 79% specificity, 90% sensitivity and 88% accuracy. A four laboratory ring study demonstrated the transferability, reliability and reproducibility of U-SENS™, with a reproducibility of 95% within laboratories and 79% between-laboratories, showing that the U-SENS™ assay is a promising tool in a skin sensitization risk assessment testing strategy. PMID:25820135

  13. Sensitivity to hepatotoxicity due to epigallocatechin gallate is affected by genetic background in diversity outbred mice

    PubMed Central

    Church, Rachel J.; Gatti, Daniel M.; Urban, Thomas J.; Long, Nanye; Yang, Xi; Shi, Qiang; Eaddy, J. Scott; Mosedale, Merrie; Ballard, Shawn; Churchill, Gary A.; Navarro, Victor; Watkins, Paul B.; Threadgill, David W.; Harrill, Alison H.

    2014-01-01

    Consumer use of herbal and dietary supplements has recently grown in the United States and, with increased use, reports of rare adverse reactions have emerged. One such supplement is green tea extract, containing the polyphenol epigallocatechin gallate (EGCG), which has been shown to be hepatotoxic at high doses in animal models. The Drug-Induced Liver Injury Network has identified multiple patients who have experienced liver injury ascribed to green tea extract consumption and the relationship to dose has not been straightforward, indicating that differences in sensitivity may contribute to the adverse response in susceptible people. The Diversity Outbred (DO), a genetically heterogeneous mouse population, provides a potential platform for study of interindividual toxicity responses to green tea extract. Within the DO population, an equal exposure to EGCG (50 mg/kg; daily for three days) was found to be tolerated in the majority of mice; however, a small fraction of the animals (16%; 43/272) exhibited severe hepatotoxicity (10–86.8% liver necrosis) that is analogous to the clinical cases. The data indicate that the DO mice may provide a platform for informing risk of rare, adverse reactions that may occur in consumer populations upon ingestion of concentrated herbal products. PMID:25446466

  14. The type B brevetoxin (PbTx-3) adversely affects development, cardiovascular function, and survival in Medaka (Oryzias latipes) embryos.

    PubMed Central

    Colman, Jamie R; Ramsdell, John S

    2003-01-01

    Brevetoxins are produced by the red tide dinoflagellate Karenia brevis. The toxins are lipophilic polyether toxins that elicit a myriad of effects depending on the route of exposure and the target organism. Brevetoxins are therefore broadly toxic to marine and estuarine animals. By mimicking the maternal route of exposure to the oocytes in finfish, we characterized the adverse effects of the type B brevetoxin brevetoxin-3 (PbTx-3) on embryonic fish development and survival. The Japanese rice fish, medaka (Oryzias latipes), was used as the experimental model in which individual eggs were exposed via microinjection to various known concentrations of PbTx-3 dissolved in an oil vehicle. Embryos injected with doses exceeding 1.0 ng/egg displayed tachycardia, hyperkinetic twitches in the form of sustained convulsions, spinal curvature, clumping of the erythrocytes, and decreased hatching success. Furthermore, fish dosed with toxin were often unable to hatch in the classic tail-first fashion and emerged head first, which resulted in partial hatches and death. We determined that the LD(50) (dose that is lethal to 50% of the fish) for an injected dose of PbTx-3 is 4.0 ng/egg. The results of this study complement previous studies of the developmental toxicity of the type A brevetoxin brevetoxin-1 (PbTx-1), by illustrating in vivo the differing affinities of the two congeners for cardiac sodium channels. Consequently, we observed differing cardiovascular responses in the embryos, wherein embryos exposed to PbTx-3 exhibited persistent tachycardia, whereas embryos exposed to PbTx-1 displayed bradycardia, the onset of which was delayed. PMID:14644667

  15. Sensitivity of Polygonum aviculare Seeds to Light as Affected by Soil Moisture Conditions

    PubMed Central

    Batlla, Diego; Nicoletta, Marcelo; Benech-Arnold, Roberto

    2007-01-01

    Background and Aims It has been hypothesized that soil moisture conditions could affect the dormancy status of buried weed seeds, and, consequently, their sensitivity to light stimuli. In this study, an investigation is made of the effect of different soil moisture conditions during cold-induced dormancy loss on changes in the sensitivity of Polygonum aviculare seeds to light. Methods Seeds buried in pots were stored under different constant and fluctuating soil moisture environments at dormancy-releasing temperatures. Seeds were exhumed at regular intervals during storage and were exposed to different light treatments. Changes in the germination response of seeds to light treatments during storage under the different moisture environments were compared in order to determine the effect of soil moisture on the sensitivity to light of P. aviculare seeds. Key Results Seed acquisition of low-fluence responses during dormancy release was not affected by either soil moisture fluctuations or different constant soil moisture contents. On the contrary, different soil moisture environments affected seed acquisition of very low fluence responses and the capacity of seeds to germinate in the dark. Conclusions The results indicate that under field conditions, the sensitivity to light of buried weed seeds could be affected by the soil moisture environment experienced during the dormancy release season, and this could affect their emergence pattern. PMID:17430979

  16. Mutations affecting sensitivity of the cellular slime mold Dictyostelium discoideum to DNA-damaging agents.

    PubMed

    Bronner, C E; Welker, D L; Deering, R A

    1992-09-01

    We describe 22 new mutants of D. discoideum that are sensitive to DNA damage. These mutants were isolated on the basis of sensitivity to either temperature, gamma-rays, or 4-nitroquinolone-1-oxide (4NQO). The doses of gamma-rays, ultraviolet light (UV), and 4NQO required to reduce the survival of colony-forming ability of these mutants to 10% (D10) range from 2% to 100% of the D10s for the nonmutant, parent strains. For most of the mutants, those which are very sensitive to one agent are very sensitive to all agents tested and those which are moderately sensitive to one agent, are moderately sensitive to all agents tested. One mutant is sensitive only to 4NQO. Linkage relationships have been examined for 13 of these mutants. This linkage information was used to design complementation tests to determine allelism with previously characterized complementation groups affecting sensitivity to radiation. 4 of the new mutants fall within previously identified complementation groups and 3 new complementation groups have been identified (radJ, radK and radL). Other new loci probably also exist among these new mutants. This brings the number of characterized mutants of D. discoideum which are sensitive to DNA-damaging agents to 33 and the number of assigned complementation groups to 11. PMID:1380652

  17. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

    PubMed Central

    Machado, Natalia P.; dos Reis Neto, Edgard Torres; Soares, Maria Roberta M. P.; Freitas, Daniele S.; Porro, Adriana; Ciconelli, Rozana M.; Pinheiro, Marcelo M.

    2013-01-01

    OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. PMID:24141833

  18. From specificity to sensitivity: affective states modulate visual working memory for emotional expressive faces

    PubMed Central

    Maran, Thomas; Sachse, Pierre; Furtner, Marco

    2015-01-01

    Previous findings suggest that visual working memory (VWM) preferentially remembers angry looking faces. However, the meaning of facial actions is construed in relation to context. To date, there are no studies investigating the role of perceiver-based context when processing emotional cues in VWM. To explore the influence of affective context on VWM for faces, we conducted two experiments using both a VWM task for emotionally expressive faces and a mood induction procedure. Affective context was manipulated by unpleasant (Experiment 1) and pleasant (Experiment 2) IAPS pictures in order to induce an affect high in motivational intensity (defensive or appetitive, respectively) compared to a low arousal control condition. Results indicated specifically increased sensitivity of VWM for angry looking faces in the neutral condition. Enhanced VWM for angry faces was prevented by inducing affects of high motivational intensity. In both experiments, affective states led to a switch from specific enhancement of angry expressions in VWM to an equally sensitive representation of all emotional expressions. Our findings demonstrate that emotional expressions are of different behavioral relevance for the receiver depending on the affective context, supporting a functional organization of VWM along with flexible resource allocation. In VWM, stimulus processing adjusts to situational requirements and transitions from a specifically prioritizing default mode in predictable environments to a sensitive, hypervigilant mode in exposure to emotional events. PMID:26379609

  19. Peer Rated Therapeutic Talent and Affective Sensitivity: A Multiple Regression Approach.

    ERIC Educational Resources Information Center

    Jackson, Eugene

    1985-01-01

    Used peer rated measures of Warmth, Understanding and Openness to predict scores on the Kagan Affective Sensitivity Scale-E80 among 66 undergraduates who had participated in interpersonal skills training groups. Results indicated that, as an additively composite index of Therapeutic Talent, they were positively correlated with affective…

  20. Do sedentary motives adversely affect physical activity? Adding cross-behavioural cognitions to the theory of planned behaviour.

    PubMed

    Rhodes, Ryan E; Blanchard, Chris M

    2008-01-01

    The purpose of this study was to explore whether sedentary behavior cognitions explain physical activity (PA) intention and behavior when integrated within the theory of planned behavior framework (TPB). A random community sample of 206 adults and a sample of 174 undergraduate students completed measures of the TPB pertaining to PA and four popular leisure-time behaviors (TV viewing, computer use, sedentary hobbies, and sedentary socializing) and an adapted Godin Leisure-Time Exercize Questionnaire (community sample = cross-sectional, undergraduate sample = 2-week prospective). Results using ordinary least squares regression provided evidence that TV viewing intention explains additional variance in PA behavior, and affective attitude (community sample) and perceived behavioral control (undergraduate sample) towards TV viewing explains additional variance in PA intention even after controlling for PA-related TPB constructs. These results underscore the potential value of adding sedentary control interventions in concert with PA promotion.

  1. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties.

    PubMed

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus; Andersen, Klaus Ejner

    2011-06-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens in ethanolic liposomes have been reported to enhance allergenicity compared with the allergens in similar vehicles without liposomes. The present report includes data on more sensitization studies using the mouse local lymph node assay with three contact allergens encapsulated in different dermal drug-delivery systems: liposomes, ethosomes, and polycaprolactone particles. The results show that the drug-delivery systems are not sensitizers in themselves. Encapsulating the hydrophilic contact allergen potassium dichromate in all three drug-delivery systems did not affect the sensitizing capacity of potassium dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed for encapsulating isoeugenol in polycaprolactone (1100 ± 406) compared with a formulation in acetone:olive oil (4491 ± 819) and in liposomes (3668 ± 950). Further, the size of DNCB-loaded liposomes did not affect the sensitizing properties. These results suggest that modern dermal drug-delivery systems may in some cases magnify or decrease the sensitizing capacity of the encapsulated contact allergen.

  2. Tail regeneration and ependymal outgrowth in the adult newt, Notophthalmus viridescens, are adversely affected by experimentally produced ischemia.

    PubMed

    Tassava, Roy A; Huang, Yan

    2005-12-01

    Spinal axons of the adult newt will regenerate when the spinal cord is severed or when the tail is amputated. Ischemia and associated hypoxia have been correlated with poor central nervous system regeneration in mammals. To test the effects of ischemia on newt spinal cord regeneration, the spinal cord and major blood vessels of the newt tail were severed 2 cm caudal to the cloaca as a primary injury. This primary injury severely reduced circulation in the caudal direction for 7 days; by day 8, circulation was largely restored. After various periods of time after primary injury, tails were amputated 1 cm caudal to the primary injury (in the area of ischemia) and tested for regeneration. If the tail was amputated within 5 days of the primary injury, regeneration did not occur. If amputation was 7 days or longer after the primary injury, a regenerative response occurred. Histology showed that in the non-regenerating tails the spinal cord and associated ependyma, known to be important to tail regeneration, had degenerated in the rostral direction. Such degeneration was prevented when tails were first amputated and allowed to form blastemas before the primary injury. The data indicate that the first 5-7 days of blastema formation are particularly sensitive to compromised blood flow (ischemia/hypoxia). It follows that mechanisms must be present in the adult newt to reduce ischemia to a minimum and thus allow ependymal outgrowth and tail regeneration.

  3. Diabetes in Pregnancy Adversely Affects the Expression of Glycogen Synthase Kinase-3β in the Hippocampus of Rat Neonates.

    PubMed

    Hami, Javad; Karimi, Razieh; Haghir, Hossein; Gholamin, Mehran; Sadr-Nabavi, Ariane

    2015-10-01

    Diabetes during pregnancy causes a wide range of neurodevelopmental and neurocognitive abnormalities in offspring. Glycogen synthase kinase-3 (GSK-3) is widely expressed during brain development and regulates multiple cellular processes, and its dysregulation is implicated in the pathogenesis of diverse neurodegenerative and psychological diseases. This study was designed to examine the effects of maternal diabetes on GSK-3β messenger RNA (mRNA) expression and phosphorylation in the developing rat hippocampus. Female rats were maintained diabetic from a week before pregnancy through parturition, and male offspring was killed immediately after birth. We found a significant bilateral upregulation of GSK-3β mRNA expression in the hippocampus of pups born to diabetic mothers at P0, compared to controls. Moreover, at the same time point, there was a marked bilateral increase in the phosphorylation level of GSK-3β in the diabetic group. Unlike phosphorylation levels, there was a significant upregulation in hippocampal GSK-3β mRNA expression in the insulin-treated group, when compared to controls. The present study revealed that diabetes during pregnancy strongly influences the regulation of GSK-3β in the right/left developing hippocampi. These dysregulations may be part of the cascade of events through which diabetes during pregnancy affects the newborn's hippocampal structure and function.

  4. The interaction of early life experiences with COMT val158met affects anxiety sensitivity.

    PubMed

    Baumann, C; Klauke, B; Weber, H; Domschke, K; Zwanzger, P; Pauli, P; Deckert, J; Reif, A

    2013-11-01

    The pathogenesis of anxiety disorders is considered to be multifactorial with a complex interaction of genetic factors and individual environmental factors. Therefore, the aim of this study was to examine gene-by-environment interactions of the genes coding for catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) with life events on measures related to anxiety. A sample of healthy subjects (N = 782; thereof 531 women; mean age M = 24.79, SD = 6.02) was genotyped for COMT rs4680 and MAOA-uVNTR (upstream variable number of tandem repeats), and was assessed for childhood adversities [Childhood Trauma Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and interaction effects of genotype, environment and gender on measures related to anxiety were assessed by means of regression analyses. Association analysis showed no main gene effect on either questionnaire score. A significant interactive effect of childhood adversities and COMT genotype was observed: Homozygosity for the low-active met allele and high CTQ scores was associated with a significant increment of explained ASI variance [R(2) = 0.040, false discovery rate (FDR) corrected P = 0.04]. A borderline interactive effect with respect to MAOA-uVNTR was restricted to the male subgroup. Carriers of the low-active MAOA allele who reported more aversive experiences in childhood exhibited a trend for enhanced anxious apprehension (R(2) = 0.077, FDR corrected P = 0.10). Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low-active MAOA-uVNTR alleles. PMID:24118915

  5. The interaction of early life experiences with COMT val158met affects anxiety sensitivity.

    PubMed

    Baumann, C; Klauke, B; Weber, H; Domschke, K; Zwanzger, P; Pauli, P; Deckert, J; Reif, A

    2013-11-01

    The pathogenesis of anxiety disorders is considered to be multifactorial with a complex interaction of genetic factors and individual environmental factors. Therefore, the aim of this study was to examine gene-by-environment interactions of the genes coding for catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) with life events on measures related to anxiety. A sample of healthy subjects (N = 782; thereof 531 women; mean age M = 24.79, SD = 6.02) was genotyped for COMT rs4680 and MAOA-uVNTR (upstream variable number of tandem repeats), and was assessed for childhood adversities [Childhood Trauma Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and interaction effects of genotype, environment and gender on measures related to anxiety were assessed by means of regression analyses. Association analysis showed no main gene effect on either questionnaire score. A significant interactive effect of childhood adversities and COMT genotype was observed: Homozygosity for the low-active met allele and high CTQ scores was associated with a significant increment of explained ASI variance [R(2) = 0.040, false discovery rate (FDR) corrected P = 0.04]. A borderline interactive effect with respect to MAOA-uVNTR was restricted to the male subgroup. Carriers of the low-active MAOA allele who reported more aversive experiences in childhood exhibited a trend for enhanced anxious apprehension (R(2) = 0.077, FDR corrected P = 0.10). Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low-active MAOA-uVNTR alleles.

  6. Absence of heat treatment of serum for culture medium supplementation does not adversely affect the outcome of in-vitro fertilization.

    PubMed

    Imoedemhe, D A; Sigue, A B; Pacpaco, E L; Olazo, A B; Luciano, E C

    1994-09-01

    This study was carried out to determine if not heat-treating serum prior to use for medium supplementation adversely affected in-vitro fertilization (IVF) of human oocytes. Morphologically mature human oocytes derived from 135 patients undergoing IVF treatment were studied. A total of 504 oocytes were incubated, inseminated and the resulting pronuclear oocytes cultured further in Earle's balanced salt solution (EBSS) supplemented with 10% non-heat-treated serum. Comparisons of fertilization rate and embryonic development were made between these and 687 control oocytes derived from the same patients but incubated, inseminated and resulting pronuclear oocytes cultured further in EBSS supplemented with 10% heat-treated serum. The fertilization rate of 74.4% (375/504) of oocytes handled in serum-supplemented medium that had not been heat-treated was significantly better than the rate of 67.7% (465/687) for controls (P < 0.0125). The proportion of pronucleate oocytes that cleaved was also significantly better in the non-heat-treated serum group: 270/300 (90%) versus 307/375 (81.8%) (P < 0.0025). There was no significant difference in the proportion of embryos with four or more cells at the time of embryo transfer. The results show that the absence of heat treatment of serum used to supplement culture medium has no adverse effect on the fertilization rate and short-term embryo development in vitro; hence we suggest that serum heat treatment is an unnecessary procedure and could be abandoned. PMID:7836531

  7. Development affects in vitro vascular tone and calcium sensitivity in ovine cerebral arteries

    PubMed Central

    Geary, Greg G; Osol, George J; Longo, Lawrence D

    2004-01-01

    We have shown recently that development from neonatal to adult life affects cerebrovascular tone of mouse cerebral arteries through endothelium-derived vasodilatory mechanisms. The current study tested the hypothesis that development from fetal to adult life affects cerebral artery vascular smooth muscle (VSM) [Ca2+]i sensitivity and tone through a mechanism partially dependent upon endothelium-dependent signalling. In pressurized resistance sized cerebral arteries (∼150 μm) from preterm (95 ± 2 days gestation (95 d)) and near-term (140 ± 2 days gestation (140 d)) fetuses, and non-pregnant adults, we measured vascular diameter (μm) and [Ca2+]i (nm) as a function of intravascular pressure. We repeated these studies in the presence of inhibition of nitric oxide synthase (NOS; with l-NAME), cyclo-oxygenase (COX; with indomethacin) and endothelium removal (E–). Cerebrovasculature tone (E+) was greater in arteries from 95 d fetuses and adults compared to 140 d sheep. Ca2+ sensitivity was similar in 95 d fetuses and adults, but much lower in 140 d fetuses. Removal of endothelium resulted in a reduction in lumen diameter as a function of pressure (greater tone) in all treatment groups. [Ca2+]i sensitivity differences among groups were magnified after E–. NOS inhibition decreased diameter as a function of pressure in each age group, with a significant increase in [Ca2+]i to pressure ratio only in the 140 d fetuses. Indomethacin increased tone and increased [Ca2+]i in the 140 d fetuses, but not the other age groups. Development from near-term to adulthood uncovered an interaction between NOS- and COX-sensitive substances that functioned to modulate artery diameter but not [Ca2+]i. This study suggests that development is associated with significant alterations in cerebral vascular smooth muscle (VSM), endothelium, NOS and COX responses to intravascular pressure. We speculate that these changes have important implications in the regulation of cerebral blood flow in

  8. Background complexity affects response of a looming-sensitive neuron to object motion.

    PubMed

    Silva, Ana C; McMillan, Glyn A; Santos, Cristina P; Gray, John R

    2015-01-01

    An increasing number of studies show how stimulus complexity affects the responses of looming-sensitive neurons across multiple animal taxa. Locusts contain a well-described, descending motion-sensitive pathway that is preferentially looming sensitive. However, the lobula giant movement detector/descending contralateral movement detector (LGMD/DCMD) pathway responds to more than simple objects approaching at constant, predictable trajectories. In this study, we presented Locusta migratoria with a series of complex three-dimensional visual stimuli presented while simultaneously recording DCMD activity extracellularly. In addition to a frontal looming stimulus, we used a combination of compound trajectories (nonlooming transitioning to looming) presented at different velocities and onto a simple, scattered, or progressive flow field background. Regardless of stimulus background, DCMD responses to looming were characteristic and related to previously described effects of azimuthal approach angle and velocity of object expansion. However, increasing background complexity caused reduced firing rates, delayed peaks, shorter rise phases, and longer fall phases. DCMD responded to transitions to looming with a characteristic drop in a firing rate that was relatively invariant across most stimulus combinations and occurred regardless of stimulus background. Spike numbers were higher in the presence of the scattered background and reduced in the flow field background. We show that DCMD response time to a transition depends on unique expansion parameters of the moving stimulus irrespective of background complexity. Our results show how background complexity shapes DCMD responses to looming stimuli, which is explained within a behavioral context.

  9. Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

    PubMed

    Hiscox, Stephen; Barnfather, Peter; Hayes, Edd; Bramble, Pamela; Christensen, James; Nicholson, Robert I; Barrett-Lee, Peter

    2011-02-01

    Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine-resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 μM, 0.05 μM and 0.13 μM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 μM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment.

  10. Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

    PubMed

    Hiscox, Stephen; Barnfather, Peter; Hayes, Edd; Bramble, Pamela; Christensen, James; Nicholson, Robert I; Barrett-Lee, Peter

    2011-02-01

    Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine-resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 μM, 0.05 μM and 0.13 μM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 μM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment. PMID:20354780

  11. Affectively salient meaning in random noise: a task sensitive to psychosis liability.

    PubMed

    Galdos, Mariana; Simons, Claudia; Fernandez-Rivas, Aranzazu; Wichers, Marieke; Peralta, Concepción; Lataster, Tineke; Amer, Guillermo; Myin-Germeys, Inez; Allardyce, Judith; Gonzalez-Torres, Miguel Angel; van Os, Jim

    2011-11-01

    Stable differences in the tendency to attribute meaning and emotional value to experience may represent an indicator of liability to psychosis. A brief task was developed assessing variation in detecting affectively meaningful speech (speech illusion) in neutral random signals (white noise) and the degree to which this was associated with psychometric and familial vulnerability for psychosis. Thirty patients, 28 of their siblings, and 307 controls participated. The rate of speech illusion was compared between cases and controls. In controls, the association between speech illusion and interview-based positive schizotypy was assessed. The hypothesis of a dose-response increase in rate of speech illusion across increasing levels of familial vulnerability for psychosis (controls, siblings of patients, and patients) was examined. Patients were more likely to display speech illusions than controls (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.4-11.7), also after controlling for neurocognitive variables (OR = 3.8, 95% CI = 1.04-14.1). The case-control difference was more accentuated for speech illusion perceived as affectively salient (positively or negatively appraised) than for neutrally appraised speech illusions. Speech illusion in the controls was strongly associated with positive schizotypy but not with negative schizotypy. In addition, the rate of speech illusion increased with increasing level of familial risk for psychotic disorder. The data suggest that the white noise task may be sensitive to psychometric and familial vulnerability for psychosis associated with alterations in top-down processing and/or salience attribution. PMID:20360211

  12. Mutant DISC1 affects methamphetamine-induced sensitization and conditioned place preference: a comorbidity model

    PubMed Central

    Pogorelov, Vladimir; Nomura, Jun; Kim, Jongho; Kannan, Geetha; Yang, Chunxia; Taniguchi, Yu; Abazyan, Bagrat; Valentine, Heather; Krasnova, Irina N.; Kamiya, Atsushi; Cadet, Jean Lud; Wong, Dean F.; Pletnikov, Mikhail V.

    2011-01-01

    Genetic factors involved in neuroplasticity have been implicated in major psychiatric illnesses such as schizophrenia, depression, and substance abuse. Given its extended interactome, variants in the Disrupted-In-Schizophrenia-1 (DISC1) gene could contribute to drug addiction and psychiatric diseases. Thus, we evaluated how dominant-negative mutant DISC1 influenced the neurobehavioral and molecular effects of methamphetamine (METH). Control and mutant DISC1 mice were studied before or after treatment with non-toxic escalating dose (ED) of METH. In naïve mice, we assessed METH-induced conditioned place preference (CPP), dopamine (DA) D2 receptor density and the basal and METH-induced activity of DISC1 partners, AKT and GSK-3β in the ventral striatum. In ED treated mice, 4 weeks after METH treatment, we evaluated fear conditioning, depression-like responses in forced swim test, and the basal and METH-induced activity of AKT and GSK-3β in the ventral striatum. We found impairment in METH-induced CPP, decreased DA D2 receptor density and altered METH-induced phosphorylation of AKT and GSK-3β in naïve DISC1 female mice. The ED regimen was not neurotoxic as evidenced by unaltered brain regional monoamine tissue content. Mutant DISC1 significantly delayed METH ED-produced sensitization and affected drug-induced phosphorylation of AKT and GSK-3β in female mice. Our results suggest that perturbations in DISC1 functions in the ventral striatum may impact the molecular mechanisms of reward and sensitization, contributing to comorbidity between drug abuse and major mental diseases. PMID:21315744

  13. Mutant DISC1 affects methamphetamine-induced sensitization and conditioned place preference: a comorbidity model.

    PubMed

    Pogorelov, Vladimir M; Nomura, Jun; Kim, Jongho; Kannan, Geetha; Ayhan, Yavuz; Yang, Chunxia; Taniguchi, Yu; Abazyan, Bagrat; Valentine, Heather; Krasnova, Irina N; Kamiya, Atsushi; Cadet, Jean Lud; Wong, Dean F; Pletnikov, Mikhail V

    2012-03-01

    Genetic factors involved in neuroplasticity have been implicated in major psychiatric illnesses such as schizophrenia, depression, and substance abuse. Given its extended interactome, variants in the Disrupted-In-Schizophrenia-1 (DISC1) gene could contribute to drug addiction and psychiatric diseases. Thus, we evaluated how dominant-negative mutant DISC1 influenced the neurobehavioral and molecular effects of methamphetamine (METH). Control and mutant DISC1 mice were studied before or after treatment with non-toxic escalating dose (ED) of METH. In naïve mice, we assessed METH-induced conditioned place preference (CPP), dopamine (DA) D2 receptor density and the basal and METH-induced activity of DISC1 partners, AKT and GSK-3β in the ventral striatum. In ED-treated mice, 4 weeks after METH treatment, we evaluated fear conditioning, depression-like responses in forced swim test, and the basal and METH-induced activity of AKT and GSK-3β in the ventral striatum. We found impairment in METH-induced CPP, decreased DA D2 receptor density and altered METH-induced phosphorylation of AKT and GSK-3β in naïve DISC1 female mice. The ED regimen was not neurotoxic as evidenced by unaltered brain regional monoamine tissue content. Mutant DISC1 significantly delayed METH ED-produced sensitization and affected drug-induced phosphorylation of AKT and GSK-3β in female mice. Our results suggest that perturbations in DISC1 functions in the ventral striatum may impact the molecular mechanisms of reward and sensitization, contributing to comorbidity between drug abuse and major mental diseases. PMID:21315744

  14. Factors affecting toxicity test endpoints in sensitive life stages of native Gulf of Mexico species.

    PubMed

    Echols, B S; Smith, A J; Rand, G M; Seda, B C

    2015-05-01

    Indigenous species are less commonly used in laboratory aquatic toxicity tests compared with standard test species due to (1) limited availability lack of requisite information necessary for their acclimation and maintenance under laboratory conditions and (2) lack of information on their sensitivity and the reproducibility of toxicity test results. As part of the Natural Resource Damage Assessment aquatic toxicity program in response to the Deepwater Horizon Oil incident (2010), sensitive life stages of native Gulf of Mexico species were evaluated in laboratory toxicity tests to determine the potential effects of the spill. Fish (n = 5) and invertebrates (n = 2) selected for this program include the following: the Florida pompano (Trachinotus carolinus), red drum (Sciaenops ocellatus), spotted sea trout (Cynoscion nebulosus), cobia (Rachycentron canadum), red porgy (Pagrus pagrus), blue crab (Callinectes sapidus), and the common moon jellyfish (Aurelia aurita). Initially in the program, to establish part of the background information, acute tests with reference toxicants (CdCl2, KCl, CuSO4) were performed with each species to establish data on intraspecies variability and test precision as well as identify other factors that may affect toxicity results. Median lethal concentration (LC50) values were calculated for each acute toxicity test with average LC50 values ranging from 248 to 862 mg/L for fish exposures to potassium chloride. Variability between test results was determined for each species by calculating the coefficient of variation (%CV) based on LC50 values. CVs ranged from 11.2 % for pompano (96-h LC50 value) to 74.8 % for red porgy 24-h tests. Cadmium chloride acute toxicity tests with the jellyfish A. aurita had the lowest overall CV of 3.6 %. By understanding acute toxicity to these native organisms from a compound with known toxicity ranges and the variability in test results, acute tests with nonstandard species can be better interpreted and used

  15. Factors affecting toxicity test endpoints in sensitive life stages of native Gulf of Mexico species.

    PubMed

    Echols, B S; Smith, A J; Rand, G M; Seda, B C

    2015-05-01

    Indigenous species are less commonly used in laboratory aquatic toxicity tests compared with standard test species due to (1) limited availability lack of requisite information necessary for their acclimation and maintenance under laboratory conditions and (2) lack of information on their sensitivity and the reproducibility of toxicity test results. As part of the Natural Resource Damage Assessment aquatic toxicity program in response to the Deepwater Horizon Oil incident (2010), sensitive life stages of native Gulf of Mexico species were evaluated in laboratory toxicity tests to determine the potential effects of the spill. Fish (n = 5) and invertebrates (n = 2) selected for this program include the following: the Florida pompano (Trachinotus carolinus), red drum (Sciaenops ocellatus), spotted sea trout (Cynoscion nebulosus), cobia (Rachycentron canadum), red porgy (Pagrus pagrus), blue crab (Callinectes sapidus), and the common moon jellyfish (Aurelia aurita). Initially in the program, to establish part of the background information, acute tests with reference toxicants (CdCl2, KCl, CuSO4) were performed with each species to establish data on intraspecies variability and test precision as well as identify other factors that may affect toxicity results. Median lethal concentration (LC50) values were calculated for each acute toxicity test with average LC50 values ranging from 248 to 862 mg/L for fish exposures to potassium chloride. Variability between test results was determined for each species by calculating the coefficient of variation (%CV) based on LC50 values. CVs ranged from 11.2 % for pompano (96-h LC50 value) to 74.8 % for red porgy 24-h tests. Cadmium chloride acute toxicity tests with the jellyfish A. aurita had the lowest overall CV of 3.6 %. By understanding acute toxicity to these native organisms from a compound with known toxicity ranges and the variability in test results, acute tests with nonstandard species can be better interpreted and used

  16. Affectively Salient Meaning in Random Noise: A Task Sensitive to Psychosis Liability

    PubMed Central

    Galdos, Mariana; Simons, Claudia; Fernandez-Rivas, Aranzazu; Wichers, Marieke; Peralta, Concepción; Lataster, Tineke; Amer, Guillermo; Myin-Germeys, Inez; Allardyce, Judith; Gonzalez-Torres, Miguel Angel; van Os, Jim

    2011-01-01

    Stable differences in the tendency to attribute meaning and emotional value to experience may represent an indicator of liability to psychosis. A brief task was developed assessing variation in detecting affectively meaningful speech (speech illusion) in neutral random signals (white noise) and the degree to which this was associated with psychometric and familial vulnerability for psychosis. Thirty patients, 28 of their siblings, and 307 controls participated. The rate of speech illusion was compared between cases and controls. In controls, the association between speech illusion and interview-based positive schizotypy was assessed. The hypothesis of a dose-response increase in rate of speech illusion across increasing levels of familial vulnerability for psychosis (controls, siblings of patients, and patients) was examined. Patients were more likely to display speech illusions than controls (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.4–11.7), also after controlling for neurocognitive variables (OR = 3.8, 95% CI = 1.04–14.1). The case-control difference was more accentuated for speech illusion perceived as affectively salient (positively or negatively appraised) than for neutrally appraised speech illusions. Speech illusion in the controls was strongly associated with positive schizotypy but not with negative schizotypy. In addition, the rate of speech illusion increased with increasing level of familial risk for psychotic disorder. The data suggest that the white noise task may be sensitive to psychometric and familial vulnerability for psychosis associated with alterations in top-down processing and/or salience attribution. PMID:20360211

  17. A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect

    PubMed Central

    Chang, Luke J.; Gianaros, Peter J.; Manuck, Stephen B.; Krishnan, Anjali; Wager, Tor D.

    2015-01-01

    Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high–low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion–pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional “emotion-related” regions (e.g., amygdala, insula) or resting-state networks (e.g., “salience,” “default mode”). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes. PMID:26098873

  18. The effects of an anxiety sensitivity intervention on anxiety, depression, and worry: Mediation through affect tolerances

    PubMed Central

    Norr, Aaron M.; Allan, Nicholas P.; Macatee, Richard J.; Keough, Meghan E.; Schmidt, Norman B.

    2014-01-01

    Recently there has been increased interest in emotional and physical tolerance risk factors for mood and anxiety disorders. Three tolerance risk factors that have been shown to be related are anxiety sensitivity (AS), distress tolerance (DT), and discomfort intolerance (DI). Although previous research has demonstrated these constructs are malleable, no research has investigated the effects of an AS intervention on DT or DI. Further, no studies have investigated whether changes in DT or DI play a role in mood and anxiety symptom amelioration due to an AS intervention. Participants (N=104), who were selected for elevated levels of AS, completed a single-session computer-assisted AS intervention or a control intervention and follow-up assessments at 1-week and 1-month post intervention. Results revealed that the intervention reduced AS and increased DT, but did not affect DI at the 1-week follow-up. Mediation analyses revealed that changes in AS and DT both mediated changes in symptoms (depression, anxiety, worry) due to the intervention at 1-month follow-up, however, when AS and DT were considered in the same model only the effect via AS remained significant. These results have important implications for the nature of the relationships between AS, DT, and DI as well as the specific mechanistic pathways through which an AS intervention ameliorates symptoms. PMID:24949907

  19. A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect.

    PubMed

    Chang, Luke J; Gianaros, Peter J; Manuck, Stephen B; Krishnan, Anjali; Wager, Tor D

    2015-06-01

    Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high-low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion-pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional "emotion-related" regions (e.g., amygdala, insula) or resting-state networks (e.g., "salience," "default mode"). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes. PMID:26098873

  20. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle.

    PubMed

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel; Brzezinska, Zofia; Klapcinska, Barbara; Galbo, Henrik; Gorski, Jan

    2010-09-01

    Fatty acids, which are the major cardiac fuel, are derived from lipid droplets stored in cardiomyocytes, among other sources. The heart expresses hormone-sensitive lipase (HSL), which regulates triglycerides (TG) breakdown, and the enzyme is under hormonal control. Evidence obtained from adipose tissue suggests that testosterone regulates HSL activity. To test whether this is also true in the heart, we measured HSL activity in the left ventricle of sedentary male rats that had been treated with testosterone supplementation or orchidectomy with or without testosterone substitution. Left ventricle HSL activity against TG was significantly elevated in intact rats supplemented with testosterone. HSL activity against both TG and diacylglyceride was reduced by orchidectomy, whereas testosterone replacement fully reversed this effect. Moreover, testosterone increased left ventricle free fatty acid levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid and carbohydrate metabolism.

  1. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence of the adverse effects of industrially-produced trans fatty acids (iTFA) on risk of cardiovascular disease is consistent and well documented in the scientific literature; however, the cardiovascular effects of naturally-occurring TFA synthesized in ruminant animals (rTFA), such as vaccenic ...

  2. Does the duration of lysis affect the sensitivity of the in vitro alkaline comet assay?

    PubMed

    Enciso, José Manuel; Sánchez, Oscar; López de Cerain, Adela; Azqueta, Amaya

    2015-01-01

    The alkaline comet assay is now the method of choice for measuring different kinds of DNA damage in cells. Several attempts have been made to identify and evaluate the critical points affecting the comet assay outcome, highlighting the requirement of arriving at a standardised protocol in order to be able to compare the results obtained in different laboratories. However, reports on the effect of modifying the time of lysis are lacking. Here we tested different times of lysis (from no lysis to 1 week) in control HeLa cells and HeLa cells treated with different concentrations of methyl methanesulfonate (MMS) or H2O2. We also tested different times of lysis in the comet assay combined with formamidopyrimidine DNA glycosylase (FPG) in untreated and Ro 19-8022 plus light-treated HeLa cells. The same DNA damage levels were detected in the absence of lysis or after 1h of lysis when the standard comet assay was used to detect the MMS- and H2O2-induced lesions; the response increased when longer lysis was used, up to at least 1 week. When FPG was used, a minimum lysis period of 5 min was necessary to allow the enzyme to reach the DNA; the same DNA damage levels were detected after 5 min or 1h of lysis and the response increased up to 24h. In conclusion, the time of lysis can be varied depending on the sensitivity needed in both versions of the assay, and a constant time of lysis should be used if results from different experiments or laboratories are to be compared.

  3. Inhaled lead affects lung pathology and inflammation in sensitized and control guinea pigs.

    PubMed

    Boskabady, Mohammad Hossein; Tabatabai, Sayed Abas; Farkhondeh, Tahereh

    2016-04-01

    The association between lead exposure and respiratory diseases including asthma is controversial. Some studies indicate that exposure to environmental lead pollution may cause asthma; however, there is not sufficient data in this regard. The effect of lead on lung pathological findings and serum inflammatory mediators in sensitized and non-sensitized guinea pigs exposed to inhaled lead was examined. Eleven animal groups including control, sensitized, three groups of non sensitized animals, three groups during sensitization, and three groups after sensitization exposed to aerosol of three lead concentrations (n = 6 for each group) were studied. Serum inflammatory mediators levels and lung pathological changes were evaluated. All pathological changes and serum ET-1, EPO, NO levels were significantly higher in the sensitized and non sensitized animals exposed to lead than control group (p < 0.05 to p < 0.001). There was no significant difference between non sensitized groups exposed to high lead concentration and sensitized group. Serum inflammatory mediators levels and pathological findings in sensitized groups exposed to lead both during and after sensitization were significantly higher than sensitized non exposed group (p < 0.05 to p < 0.001). The data of exposed animals to high lead concentration were significantly higher than those of medium and low concentrations; those of medium concentration were also higher than low concentration (p < 0.05 to p < 0.001). In summary, the present study indicates that exposure to inhaled lead is able to induce respiratory changes similar to asthma. In addition, the results indicated that exposure to environmental lead is able to aggravate asthma severity both during development of asthma or after its manifestation.

  4. Interactive effect of negative affectivity and anxiety sensitivity in terms of mental health among Latinos in primary care.

    PubMed

    Zvolensky, Michael J; Paulus, Daniel J; Bakhshaie, Jafar; Garza, Monica; Ochoa-Perez, Melissa; Medvedeva, Angela; Bogiaizian, Daniel; Robles, Zuzuky; Manning, Kara; Schmidt, Norman B

    2016-09-30

    From a public health perspective, primary care medical settings represent a strategic location to address mental health disapirty among Latinos. Yet, there is little empirical work that addresses affective vulnerability processes for mental health problems in such settings. To help address this gap in knowledge, the present investigation examined an interactive model of negative affectivity (tendency to experience negative mood states) and anxiety sensitivity (fear of the negative consequences of aversive sensations) among a Latino sample in primary care in terms of a relatively wide range of anxiety/depression indices. Participants included 390 Latino adults (Mage=38.7, SD=11.3; 86.9% female; 95.6% reported Spanish as first language) from a primary care health clinic. Primary dependent measures included depressive, suicidal, social anxiety, and anxious arousal symptoms, number of mood and anxiety disorders, and disability. Consistent with prediction, the interaction between negative affectivity and anxiety sensitivity was significantly related to suicidal, social anxiety, and anxious arousal symptoms, as well as number of mood/anxiety diagnoses and disability among the primary care Latino sample. The form of the interactions indicated a synergistic effect, such that the greatest levels of each outcome were found among those with high negative affectivity and high anxiety sensitivity. There was a trending interaction for depressive symptoms. Overall, these data provide novel empirical evidence suggesting that there is a clinically-relevant interplay between anxiety sensitivity and negative affectivity in regard to the expression of anxiety and depressive symptoms among a Latino primary care sample.

  5. Relations between pure dietary and dietary-negative affect subtypes and impulsivity and reinforcement sensitivity in binge eating individuals.

    PubMed

    Carrard, Isabelle; Crépin, Christelle; Ceschi, Grazia; Golay, Alain; Van der Linden, Martial

    2012-01-01

    To investigate potential predictors of the severity of binge eating disorder (BED), two subtypes of patients with the disorder, a pure dietary subtype and a dietary-negative affect subtype, were identified. This study investigated the relationships between the two subtypes and impulsivity and reinforcement sensitivity. Ninety-two women meeting threshold and subthreshold criteria for BED diagnosis filled out questionnaires to determine eating disorder severity, impulsivity and reinforcement sensitivity before and after participating in an online guided self-help program for BED. Cluster analyses revealed a pure dietary subtype (N=66, 71.7%) and a dietary-negative affect subtype (N=26, 28.3%). Compared to the pure dietary subtype, the dietary-negative affect subtype reported a higher frequency of objective binge episodes, more severe eating disorders, higher urgency scores (defined as a tendency to act rashly in the context of negative affect), a greater sensitivity to punishment, and a higher dropout rate during treatment. These findings suggest that BED patients in the dietary-negative affect subtype exhibit heightened anxiety and are highly impulsive, especially in contexts of negative affect. For these individuals, psychological interventions for BED should focus on inhibiting automatic responses to negative emotions.

  6. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  7. Adverse reactions to fragrances. A clinical review.

    PubMed

    de Groot, A C; Frosch, P J

    1997-02-01

    This article reviews side-effects of fragrance materials present in cosmetics with emphasis on clinical aspects: epidemiology, types of adverse reactions, clinical picture, diagnostic procedures, and the sensitizers. Considering the ubiquitous occurrence of fragrance materials, the risk of side-effects is small. In absolute numbers, however, fragrance allergy is common, affecting approximately 1% of the general population. Although a detailed profile of patients sensitized to fragrances needs to be elucidated, common features of contact allergy are: axillary dermatitis, dermatitis of the face (including the eyelids) and neck, well-circumscribed patches in areas of "dabbing-on" perfumes (wrists, behind the ears) and (aggravation of) hand eczema. Depending on the degree of sensitivity, the severity of dermatitis may range from mild to severe with dissemination and even erythroderma. Airborne or "connubial" contact dermatitis should always be suspected. Other less frequent adverse reactions to fragrances are photocontact dermatitis, immediate contact reactions and pigmentary changes. The fragrance mix, although very useful for the detection of sensitive patients, both causes false-positive and false-negative reactions, and detects only 70% of perfume-allergic patients. Therefore, future research should be directed at increasing the sensitivity and the specificity of the mix. Relevance is said to be established in 50-65% of positive reactions, but accurate criteria are needed. Suggestions are made for large-scale investigation of several fragrances on the basis of literature data and frequency of use in cosmetics. The literature on adverse reactions to balsam of Peru (an indicator for fragrance sensitivity), essential oils (which currently appear to be used more in aromatherapy than in perfumery) and on fragrances used as flavours and spices in foods and beverages is not discussed in detail, but pertinent side-effects data are tabulated and relevant literature is

  8. Sensitivity Analysis of Parameters Affecting Protection of Water Resources at Hanford WA

    SciTech Connect

    DAVIS, J.D.

    2002-02-08

    The scope of this analysis was to assess the sensitivity of contaminant fluxes from the vadose zone to the water table, to several parameters, some of which can be controlled by operational considerations.

  9. How does the sensitivity of climate affect stratospheric solar radiation management?

    NASA Astrophysics Data System (ADS)

    Ricke, K.; Rowlands, D. J.; Ingram, W.; Keith, D.; Morgan, M. G.

    2011-12-01

    If implementation of proposals to engineer the climate through solar radiation management (SRM) ever occurs, it is likely to be contingent upon climate sensitivity. Despite this, no modeling studies have examined how the effectiveness of SRM forcings differs between the typical Atmosphere-Ocean General Circulation Models (AOGCMs) with climate sensitivities close to the Coupled Model Intercomparison Project (CMIP) mean and ones with high climate sensitivities. Here, we use a perturbed physics ensemble modeling experiment to examine variations in the response of climate to SRM under different climate sensitivities. When SRM is used as a substitute for mitigation its ability to maintain the current climate state gets worse with increased climate sensitivity and with increased concentrations of greenhouse gases. However, our results also demonstrate that the potential of SRM to slow climate change, even at the regional level, grows with climate sensitivity. On average, SRM reduces regional rates of temperature change by more than 90 percent and rates of precipitation change by more than 50 percent in these higher sensitivity model configurations. To investigate how SRM might behave in models with high climate sensitivity that are also consistent with recent observed climate change we perform a "perturbed physics" ensemble (PPE) modelling experiment with the climateprediction.net (cpdn) version of the HadCM3L AOGCM. Like other perturbed physics climate modelling experiments, we simulate past and future climate scenarios using a wide range of model parameter combinations that both reproduce past climate within a specified level of accuracy and simulate future climates with a wide range of climate sensitivities. We chose 43 members ("model versions") from a subset of the 1,550 from the British Broadcasting Corporation (BBC) climateprediction.net project that have data that allow restarts. We use our results to explore how much assessments of SRM that use best

  10. Intrinsic factors that can affect sensitivity to chromosome-aberration induction

    SciTech Connect

    Preston, R.J.

    1982-01-01

    The paper addresses the question, are there individuals who are hypersensitive, or are more likely to be hypersensitive, to the induction of chromosome aberrations by radiation and chemicals. Lymphocytes of persons heterozygous for xeroderma pigmentosum, ataxia telangiectasia, and Fauconi's anemia were subjected to chemical and/or ionizing radiations to determine their sensitivity to chromosome aberration induction. In the majority of cases the sensitivity was intermediate between that of normal individuals and homozygotes for these genes. (ACR)

  11. Alcohol Use in College Students as a Function of Reinforcement Sensitivity, Life Events, and Affect

    ERIC Educational Resources Information Center

    Lee, Hyoung Suk

    2010-01-01

    Mood has been commonly viewed as an important determinant of drinking, but studies of positive and negative affect and alcohol use have reported inconsistent results. It has been suggested that the relationship between negative affect and heavy drinking or drinking problems depends on individual vulnerability dimensions such as personality. Gray's…

  12. Development and Validation of Children's Environmental Affect (Attitude, Sensitivity and Willingness to Take Action) Scale

    ERIC Educational Resources Information Center

    Erdogan, Mehmet; Marcinkowski, Thomas

    2015-01-01

    This study focuses on the design, development, validation, and psychometric properties of the Children's Environmental Affect Scale (CEAS). The following steps were taken in developing the CEAS. A substantial review of literature on environmental affect and EL helped the researchers identify several scales and questionnaires that, in turn, help…

  13. High d(+)-fructose diet adversely affects testicular weight gain in weaning rats─protection by moderate d(+)-glucose diet.

    PubMed

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2013-01-01

    The use of high D(+)-fructose corn syrup has increased over the past several decades in the developed countries, while overweight and obesity rates and the related diseases have risen dramatically. However, we found that feeding a high D(+)-fructose diet (80% D(+)-fructose as part of the diet) to weaning rats for 21 days led to reduced food intake (50% less, P < 0.0001) and thus delayed the weight gains in the body (40% less, P < 0.0001) and testes (40% less, P < 0.0001) compared to the no D(+)-fructose diet. We also challenged a minimum requirement of dietary D(+)-glucose for preventing the adverse effects of D(+)-fructose, such as lower food intake and reduction of body weight and testicular weight; the minimum requirement of D(+)-glucose was ≈23% of the diet. This glucose amount may be the minimum requirement of exogenous glucose for reducing weight gain. PMID:23935370

  14. Interactive effect of negative affectivity and anxiety sensitivity in terms of mental health among Latinos in primary care.

    PubMed

    Zvolensky, Michael J; Paulus, Daniel J; Bakhshaie, Jafar; Garza, Monica; Ochoa-Perez, Melissa; Medvedeva, Angela; Bogiaizian, Daniel; Robles, Zuzuky; Manning, Kara; Schmidt, Norman B

    2016-09-30

    From a public health perspective, primary care medical settings represent a strategic location to address mental health disapirty among Latinos. Yet, there is little empirical work that addresses affective vulnerability processes for mental health problems in such settings. To help address this gap in knowledge, the present investigation examined an interactive model of negative affectivity (tendency to experience negative mood states) and anxiety sensitivity (fear of the negative consequences of aversive sensations) among a Latino sample in primary care in terms of a relatively wide range of anxiety/depression indices. Participants included 390 Latino adults (Mage=38.7, SD=11.3; 86.9% female; 95.6% reported Spanish as first language) from a primary care health clinic. Primary dependent measures included depressive, suicidal, social anxiety, and anxious arousal symptoms, number of mood and anxiety disorders, and disability. Consistent with prediction, the interaction between negative affectivity and anxiety sensitivity was significantly related to suicidal, social anxiety, and anxious arousal symptoms, as well as number of mood/anxiety diagnoses and disability among the primary care Latino sample. The form of the interactions indicated a synergistic effect, such that the greatest levels of each outcome were found among those with high negative affectivity and high anxiety sensitivity. There was a trending interaction for depressive symptoms. Overall, these data provide novel empirical evidence suggesting that there is a clinically-relevant interplay between anxiety sensitivity and negative affectivity in regard to the expression of anxiety and depressive symptoms among a Latino primary care sample. PMID:27359301

  15. UV wavelengths experienced during development affect larval newt visual sensitivity and predation efficiency.

    PubMed

    Martin, Mélissa; Théry, Marc; Rodgers, Gwendolen; Goven, Delphine; Sourice, Stéphane; Mège, Pascal; Secondi, Jean

    2016-02-01

    We experimentally investigated the influence of developmental plasticity of ultraviolet (UV) visual sensitivity on predation efficiency of the larval smooth newt, Lissotriton vulgaris. We quantified expression of SWS1 opsin gene (UV-sensitive protein of photoreceptor cells) in the retinas of individuals who had developed in the presence (UV+) or absence (UV-) of UV light (developmental treatments), and tested their predation efficiency under UV+ and UV- light (testing treatments). We found that both SWS1 opsin expression and predation efficiency were significantly reduced in the UV- developmental group. Larvae in the UV- testing environment displayed consistently lower predation efficiency regardless of their developmental treatment. These results prove for the first time, we believe, functional UV vision and developmental plasticity of UV sensitivity in an amphibian at the larval stage. They also demonstrate that UV wavelengths enhance predation efficiency and suggest that the magnitude of the behavioural response depends on retinal properties induced by the developmental lighting environment.

  16. UV wavelengths experienced during development affect larval newt visual sensitivity and predation efficiency.

    PubMed

    Martin, Mélissa; Théry, Marc; Rodgers, Gwendolen; Goven, Delphine; Sourice, Stéphane; Mège, Pascal; Secondi, Jean

    2016-02-01

    We experimentally investigated the influence of developmental plasticity of ultraviolet (UV) visual sensitivity on predation efficiency of the larval smooth newt, Lissotriton vulgaris. We quantified expression of SWS1 opsin gene (UV-sensitive protein of photoreceptor cells) in the retinas of individuals who had developed in the presence (UV+) or absence (UV-) of UV light (developmental treatments), and tested their predation efficiency under UV+ and UV- light (testing treatments). We found that both SWS1 opsin expression and predation efficiency were significantly reduced in the UV- developmental group. Larvae in the UV- testing environment displayed consistently lower predation efficiency regardless of their developmental treatment. These results prove for the first time, we believe, functional UV vision and developmental plasticity of UV sensitivity in an amphibian at the larval stage. They also demonstrate that UV wavelengths enhance predation efficiency and suggest that the magnitude of the behavioural response depends on retinal properties induced by the developmental lighting environment. PMID:26843556

  17. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera.

    PubMed

    Rinkevich, Frank D; Margotta, Joseph W; Pittman, Jean M; Danka, Robert G; Tarver, Matthew R; Ottea, James A; Healy, Kristen B

    2015-01-01

    The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (<1-fold), moderate differences in pyrethroid bioassays (1.5 to 3-fold), and dramatic differences in neonicotinoid bioassays (3.4 to 33.3-fold). Synergism bioassays with piperonyl butoxide, amitraz, and coumaphos showed increased phenothrin sensitivity in all stocks and also demonstrated further physiological differences between stocks. In addition, as bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature. PMID

  18. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera.

    PubMed

    Rinkevich, Frank D; Margotta, Joseph W; Pittman, Jean M; Danka, Robert G; Tarver, Matthew R; Ottea, James A; Healy, Kristen B

    2015-01-01

    The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (<1-fold), moderate differences in pyrethroid bioassays (1.5 to 3-fold), and dramatic differences in neonicotinoid bioassays (3.4 to 33.3-fold). Synergism bioassays with piperonyl butoxide, amitraz, and coumaphos showed increased phenothrin sensitivity in all stocks and also demonstrated further physiological differences between stocks. In addition, as bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature.

  19. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera

    PubMed Central

    Rinkevich, Frank D.; Margotta, Joseph W.; Pittman, Jean M.; Danka, Robert G.; Tarver, Matthew R.; Ottea, James A.; Healy, Kristen B.

    2015-01-01

    The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (<1-fold), moderate differences in pyrethroid bioassays (1.5 to 3-fold), and dramatic differences in neonicotinoid bioassays (3.4 to 33.3-fold). Synergism bioassays with piperonyl butoxide, amitraz, and coumaphos showed increased phenothrin sensitivity in all stocks and also demonstrated further physiological differences between stocks. In addition, as bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature. PMID

  20. Clonal differences in IgE antibodies affect cutaneous anaphylaxis-associated thermal sensitivity in mice

    PubMed Central

    Mack, Madison; Tonc, Elena; Ashbaugh, Alyssa; Wetzel, Abigail; Sykes, Akilah; Engblom, Camilla; Shabani, Estela; Mora-Solano, Carolina; Trier, Anna; Swanson, Linnea; Ewan, Emily; Martinov, Tijana; Chatterjea, Devavani

    2014-01-01

    Cellular and molecular mediators of immune responses are increasingly implicated in acute and chronic pain pathophysiologies. Here we demonstrate that passive cutaneous IgE/Ag anaphylaxis provokes increased thermal sensitivity in the hind paw tissue of mice. The murine anti-DNP IgE antibodies SPE-7 and ε26 are known to induce differential cytokine production in bone marrow cultured mast cells in vitro without antigen challenge. We found a novel, antigen-dependent heterogeneity in the thermal pain responses elicited in the hind paws between SPE-7 and ε26 sensitized DNP-challenged mice. Mice experienced pronounced hind paw thermal sensitivity lasting 6 hours after DNP challenge when sensitized with SPE-7 but not ε26 IgE. The two IgE clones induced equivalent hind paw edema, neutrophil influx, cytokine production, and reduction in tissue histamine content in vivo, and bound to the same or overlapping epitopes on the DNP antigen in vitro. Therefore IgE antibodies against the same antigen can induce comparable inflammation, yet contribute to markedly different anaphylaxis-associated pain within an allergic response, suggesting that non-canonical IgE binding partners such as sensory neurons may play a role in allergy-related pain responses. PMID:25149207

  1. Sensitivity and other factors affecting biospecific desorption in chromatography of proteins. A study by computer simulation.

    PubMed Central

    Yon, R J

    1980-01-01

    Some theoretical aspects of the desorption of a column-bound protein by elution with its biospecific ligand are considered in cases where, in comparison with the unliganded protein, the protein-ligand complex has a diminished but finite affinity for the adsorbent. A quantity termed the biospecific sensitivity, B, is introduced to facilitate comparison between different systems. Biospecific sensitivity may be defined as the fractional change in standard free energy of adsorption on formation of the protein-ligand complex. The effects of a moderate-to-low biospecific sensitivity on theoretical desorption profiles have been examined by using a computer simulation of the classical multiple-plate column model. Desorption was simulated under various boundary conditions involving protein-adsorbent and protein-ligand affinities and the initial concentrations of adsorption sites, protein and ligand. These simulations suggest that, when the biospecific sensitivity is low, desorption is optimized if (a) the unliganded protein is adsorbed as weakly as possible, (b) the column is loaded to near-saturation with the required protein, (c) the free ligand concentration is many times greater than that giving near-saturation of the protein in free solution, and (d) protein contaminants with high affinity for the adsorbent, and present in large amount, are removed in preliminary purification steps. PMID:7378048

  2. Migration, neighborhoods, and networks: approaches to understanding how urban environmental conditions affect syndemic adverse health outcomes among gay, bisexual and other men who have sex with men.

    PubMed

    Egan, James E; Frye, Victoria; Kurtz, Steven P; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A

    2011-04-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM.

  3. Migration, Neighborhoods, and Networks: Approaches to Understanding How Urban Environmental Conditions Affect Syndemic Adverse Health Outcomes Among Gay, Bisexual and Other Men Who Have Sex with Men

    PubMed Central

    Egan, James E.; Kurtz, Steven P.; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A.

    2011-01-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  4. Rock glacier outflows may adversely affect lakes: lessons from the past and present of two neighboring water bodies in a crystalline-rock watershed.

    PubMed

    Ilyashuk, Boris P; Ilyashuk, Elena A; Psenner, Roland; Tessadri, Richard; Koinig, Karin A

    2014-06-01

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake's history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years.

  5. Migration, neighborhoods, and networks: approaches to understanding how urban environmental conditions affect syndemic adverse health outcomes among gay, bisexual and other men who have sex with men.

    PubMed

    Egan, James E; Frye, Victoria; Kurtz, Steven P; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A

    2011-04-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  6. Rock Glacier Outflows May Adversely Affect Lakes: Lessons from the Past and Present of Two Neighboring Water Bodies in a Crystalline-Rock Watershed

    PubMed Central

    2014-01-01

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake’s history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years. PMID:24804777

  7. Synthetic progestins medroxyprogesterone acetate and dydrogesterone and their binary mixtures adversely affect reproduction and lead to histological and transcriptional alterations in zebrafish (Danio rerio).

    PubMed

    Zhao, Yanbin; Castiglioni, Sara; Fent, Karl

    2015-04-01

    Medroxyprogesterone acetate (MPA) and dydrogesterone (DDG) are synthetic progestins widely used in human and veterinary medicine. Although aquatic organisms are exposed to them through wastewater and animal farm runoff, very little is known about their effects in the environment. Here we provide a comprehensive analysis of the responses of zebrafish (Danio rerio) to MPA, DDG, and their binary mixtures at measured concentrations between 4.5 and 1663 ng/L. DDG and both mixtures impaired reproductive capacities (egg production) of breeding pairs and led to histological alterations of ovaries and testes and increased gonadosomatic index. Transcriptional analysis of up to 28 genes belonging to different pathways demonstrated alterations in steroid hormone receptors, steroidogenesis enzymes, and specifically, the circadian rhythm genes, in different organs of adult zebrafish and eleuthero-embryos. Alterations occurred even at environmentally relevant concentrations of 4.5-4.8 ng/L MPA, DDG and the mixture in eleuthero-embryos and at 43-89 ng/L in adult zebrafish. Additionally, the mixtures displayed additive effects in most but not all parameters in adults and eleuthero-embryos, suggesting concentration addition. Our data suggest that MPA and DDG and their mixtures induce multiple transcriptional responses at environmentally relevant concentrations and adverse effects on reproduction and gonad histology at higher levels.

  8. Low-Temperature Sensitization Behavior of Base, Heat-Affected Zone, and Weld Pool in AISI 304LN

    NASA Astrophysics Data System (ADS)

    Singh, Raghuvir; Das, Gautam; Singh, P. K.; Chattoraj, I.

    2009-05-01

    Present investigations were focused on low-temperature sensitization (LTS) behavior of 304LN stainless steels considered from pipes of two different thicknesses. The specimens for the present study were taken from solution-annealed pipes (of varying thicknesses) and welded pipes (including the heat-affected zone (HAZ)). The specimens were subjected to thermal aging at 400 °C and 450 °C for different durations ranging from 125 to 8000 hours, to evaluate their sensitization susceptibility. The aging durations were worked out to simulate the 30-to-100-year life of the studied stainless steel at 300 °C using the Arrheneous equation and considering the activation energy of 150 kJ/mol. The thermally aged specimens were characterized for their degree of sensitization (DOS) and susceptibility to intergranular corrosion (IGC) by double-loop (DL) electrochemical potentiokinetic reactivation (EPR) and by methods given in the ASTM A262 practices A and E. It has been clearly shown that the weld pool is more sensitive to IGC than are the base and the HAZ at both the aging temperatures (LTS), because they showed IGC cracks during the bending subsequent to the boiling in H2SO4-CuSO4 solution. Both the base and the HAZ of the thicker pipe material showed susceptibility to sensitization, as indicated by the increasing DOS and “dual-type” microstructure during electrolytic oxalic acid (EOA) etching; however, they were found safe from IGC for the studied sensitization times. The susceptibility to sensitization and IGC in the weld pool is related to the presence of copious delta ferrite with chromium diffusivity that is accelerated compared to the austenite phase. The time-temperature-sensitization (TTS) curves were prepared accordingly, based on these results.

  9. Thermo Sensitivity of Polysiloxane/Silica Nanocomposites Affected by the Structure of Polymer-Filler Interface.

    PubMed

    Zhang, Qian; Zhou, Yufeng; Yu, Fengmei; Song, Lixian; Sun, Sumin; Lu, Zhongyuan; Lu, Ai

    2016-03-01

    In this work thermo sensitivity was investigated with the bound rubber theory and thermoelasticity theory of the polymer-filler interface interaction between Polymethylvinylsiloxane (PMVS) and nanofillers (fumed and precipitated silica with the primary particle size of 10 nanometres). Bound rubber (the transition phase between PMVS and silica) content was measured by sol-gel analysis and swelling experiments. Results showed that the amount of bound rubber increases steadily with the increases of filler content. But the increasing rate suddenly decreased at certain silica content (between 40 and 50 phr of precipitated silica and between 30 and 40 phr of fumed silica, respectively), which was constant with the thermoelaticity experiment results. The temperature coefficients in low strain uniaxial extension are found to present sudden changing at the same silica content. This observation shows that thermo sensitivity is closely connected with the structure of polymer-filler interface. PMID:27455698

  10. Charge and geometry of residues in the loop 2 β hairpin differentially affect agonist and ethanol sensitivity in glycine receptors.

    PubMed

    Perkins, Daya I; Trudell, James R; Asatryan, Liana; Davies, Daryl L; Alkana, Ronald L

    2012-05-01

    Recent studies highlighted the importance of loop 2 of α1 glycine receptors (GlyRs) in the propagation of ligand-binding energy to the channel gate. Mutations that changed polarity at position 52 in the β hairpin of loop 2 significantly affected sensitivity to ethanol. The present study extends the investigation to charged residues. We found that substituting alanine with the negative glutamate at position 52 (A52E) significantly left-shifted the glycine concentration response curve and increased sensitivity to ethanol, whereas the negative aspartate substitution (A52D) significantly right-shifted the glycine EC₅₀ but did not affect ethanol sensitivity. It is noteworthy that the uncharged glutamine at position 52 (A52Q) caused only a small right shift of the glycine EC₅₀ while increasing ethanol sensitivity as much as A52E. In contrast, the shorter uncharged asparagine (A52N) caused the greatest right shift of glycine EC₅₀ and reduced ethanol sensitivity to half of wild type. Collectively, these findings suggest that charge interactions determined by the specific geometry of the amino acid at position 52 (e.g., the 1-Å chain length difference between aspartate and glutamate) play differential roles in receptor sensitivity to agonist and ethanol. We interpret these results in terms of a new homology model of GlyR based on a prokaryotic ion channel and propose that these mutations form salt bridges to residues across the β hairpin (A52E-R59 and A52N-D57). We hypothesize that these electrostatic interactions distort loop 2, thereby changing agonist activation and ethanol modulation. This knowledge will help to define the key physical-chemical parameters that cause the actions of ethanol in GlyRs.

  11. Factors Affecting Sensitivity to Frequency Change in School-Age Children and Adults

    ERIC Educational Resources Information Center

    Buss, Emily; Taylor, Crystal N.; Leibold, Lori J.

    2014-01-01

    Purpose: The factors affecting frequency discrimination in school-age children are poorly understood. The goal of the present study was to evaluate developmental effects related to memory for pitch and the utilization of temporal fine structure. Method: Listeners were 5.1- to 13.6-year-olds and adults, all with normal hearing. A subgroup of…

  12. 2.45-GHz microwave irradiation adversely affects reproductive function in male mouse, Mus musculus by inducing oxidative and nitrosative stress.

    PubMed

    Shahin, S; Mishra, V; Singh, S P; Chaturvedi, C M

    2014-05-01

    Electromagnetic radiations are reported to produce long-term and short-term biological effects, which are of great concern to human health due to increasing use of devices emitting EMR especially microwave (MW) radiation in our daily life. In view of the unavoidable use of MW emitting devices (microwaves oven, mobile phones, Wi-Fi, etc.) and their harmful effects on biological system, it was thought worthwhile to investigate the long-term effects of low-level MW irradiation on the reproductive function of male Swiss strain mice and its mechanism of action. Twelve-week-old mice were exposed to non-thermal low-level 2.45-GHz MW radiation (CW for 2 h/day for 30 days, power density = 0.029812 mW/cm(2) and SAR = 0.018 W/Kg). Sperm count and sperm viability test were done as well as vital organs were processed to study different stress parameters. Plasma was used for testosterone and testis for 3β HSD assay. Immunohistochemistry of 3β HSD and nitric oxide synthase (i-NOS) was also performed in testis. We observed that MW irradiation induced a significant decrease in sperm count and sperm viability along with the decrease in seminiferous tubule diameter and degeneration of seminiferous tubules. Reduction in testicular 3β HSD activity and plasma testosterone levels was also noted in the exposed group of mice. Increased expression of testicular i-NOS was observed in the MW-irradiated group of mice. Further, these adverse reproductive effects suggest that chronic exposure to nonionizing MW radiation may lead to infertility via free radical species-mediated pathway. PMID:24490664

  13. 2.45-GHz microwave irradiation adversely affects reproductive function in male mouse, Mus musculus by inducing oxidative and nitrosative stress.

    PubMed

    Shahin, S; Mishra, V; Singh, S P; Chaturvedi, C M

    2014-05-01

    Electromagnetic radiations are reported to produce long-term and short-term biological effects, which are of great concern to human health due to increasing use of devices emitting EMR especially microwave (MW) radiation in our daily life. In view of the unavoidable use of MW emitting devices (microwaves oven, mobile phones, Wi-Fi, etc.) and their harmful effects on biological system, it was thought worthwhile to investigate the long-term effects of low-level MW irradiation on the reproductive function of male Swiss strain mice and its mechanism of action. Twelve-week-old mice were exposed to non-thermal low-level 2.45-GHz MW radiation (CW for 2 h/day for 30 days, power density = 0.029812 mW/cm(2) and SAR = 0.018 W/Kg). Sperm count and sperm viability test were done as well as vital organs were processed to study different stress parameters. Plasma was used for testosterone and testis for 3β HSD assay. Immunohistochemistry of 3β HSD and nitric oxide synthase (i-NOS) was also performed in testis. We observed that MW irradiation induced a significant decrease in sperm count and sperm viability along with the decrease in seminiferous tubule diameter and degeneration of seminiferous tubules. Reduction in testicular 3β HSD activity and plasma testosterone levels was also noted in the exposed group of mice. Increased expression of testicular i-NOS was observed in the MW-irradiated group of mice. Further, these adverse reproductive effects suggest that chronic exposure to nonionizing MW radiation may lead to infertility via free radical species-mediated pathway.

  14. Temperature-sensitive albino gene TCD5, encoding a monooxygenase, affects chloroplast development at low temperatures

    PubMed Central

    Wang, Yufeng; Zhang, Jianhui; Shi, Xiaoliang; Peng, Yu; Li, Ping; Lin, Dongzhi; Dong, Yanjun; Teng, Sheng

    2016-01-01

    Chloroplasts are essential for photosynthesis and play critical roles in plant development. In this study, we characterized the temperature-sensitive chlorophyll-deficient rice mutant tcd5, which develops albino leaves at low temperatures (20 °C) and normal green leaves at high temperatures (32 °C). The development of chloroplasts and etioplasts is impaired in tcd5 plants at 20 °C, and the temperature-sensitive period for the albino phenotype is the P4 stage of leaf development. The development of thylakoid membranes is arrested at the mid-P4 stage in tcd5 plants at 20 °C. We performed positional cloning of TCD5 and then complementation and knock-down experiments, and the results showed that the transcript LOC_Os05g34040.1 from the LOC_Os05g34040 gene corresponded to the tcd5 phenotype. TCD5 encodes a conserved plastid-targeted monooxygenase family protein which has not been previously reported associated with a temperature-sensitive albino phenotype in plants. TCD5 is abundantly expressed in young leaves and immature spikes, and low temperatures increased this expression. The transcription of some genes involved in plastid transcription/translation and photosynthesis varied in the tcd5 mutant. Although the phenotype and temperature dependence of the TCD5 orthologous mutant phenotype were different in rice and Arabidopsis, OsTCD5 could rescue the phenotype of the Arabidopsis mutant, suggesting that TCD5 function is conserved between monocots and dicots. PMID:27531886

  15. Arm dominance affects feedforward strategy more than feedback sensitivity during a postural task.

    PubMed

    Walker, Elise H E; Perreault, Eric J

    2015-07-01

    Handedness is a feature of human motor control that is still not fully understood. Recent work has demonstrated that the dominant and nondominant arm each excel at different behaviors and has proposed that this behavioral asymmetry arises from lateralization in the cerebral cortex: the dominant side specializes in predictive trajectory control, while the nondominant side is specialized for impedance control. Long-latency stretch reflexes are an automatic mechanism for regulating posture and have been shown to contribute to limb impedance. To determine whether long-latency reflexes also contribute to asymmetric motor behavior in the upper limbs, we investigated the effect of arm dominance on stretch reflexes during a postural task that required varying degrees of impedance control. Our results demonstrated slightly but significantly larger reflex responses in the biarticular muscles of the nondominant arm, as would be consistent with increased impedance control. These differences were attributed solely to higher levels of voluntary background activity in the nondominant biarticular muscles, indicating that feedforward strategies for postural stability may differ between arms. Reflex sensitivity, which was defined as the magnitude of the reflex response for matched levels of background activity, was not significantly different between arms for a broad subject population ranging from 23 to 51 years of age. These results indicate that inter-arm differences in feedforward strategies are more influential during posture than differences in feedback sensitivity, in a broad subject population. Interestingly, restricting our analysis to subjects under 40 years of age revealed a small increase in long-latency reflex sensitivity in the nondominant arm relative to the dominant arm. Though our subject numbers were small for this secondary analysis, it suggests that further studies may be required to assess the influence of reflex lateralization throughout development.

  16. Arm Dominance Affects Feedforward Strategy more than Feedback Sensitivity during a Postural Task

    PubMed Central

    Walker, Elise H. E.; Perreault, Eric J.

    2015-01-01

    Handedness is a feature of human motor control that is still not fully understood. Recent work has demonstrated that the dominant and nondominant arm each excel at different behaviors, and has proposed that this behavioral asymmetry arises from lateralization in the cerebral cortex: the dominant side specializes in predictive trajectory control, while the nondominant side is specialized for impedance control. Long-latency stretch reflexes are an automatic mechanism for regulating posture, and have been shown to contribute to limb impedance. To determine whether long-latency reflexes also contribute to asymmetric motor behavior in the upper limbs, we investigated the effect of arm dominance on stretch reflexes during a postural task that required varying degrees of impedance control. Our results demonstrated slightly but significantly larger reflex responses in the biarticular muscles of the nondominant arm, as would be consistent with increased impedance control. These differences were attributed solely to higher levels of voluntary background activity in the nondominant biarticular muscles, indicating that feedforward strategies for postural stability may differ between arms. Reflex sensitivity, which was defined as the magnitude of the reflex response for matched levels of background activity, was not significantly different between arms for a broad subject population ranging from 23–51 years of age. These results indicate that inter-arm differences in feedforward strategies are more influential during posture than differences in feedback sensitivity, in a broad subject population. Interestingly, restricting our analysis to subjects under 40 years of age revealed a small increase in long-latency reflex sensitivity in the nondominant arm relative to the dominant arm. Though our subject numbers were small for this secondary analysis, it suggests that further studies may be required to assess the influence of reflex lateralization throughout development. PMID

  17. Temperature-sensitive albino gene TCD5, encoding a monooxygenase, affects chloroplast development at low temperatures.

    PubMed

    Wang, Yufeng; Zhang, Jianhui; Shi, Xiaoliang; Peng, Yu; Li, Ping; Lin, Dongzhi; Dong, Yanjun; Teng, Sheng

    2016-09-01

    Chloroplasts are essential for photosynthesis and play critical roles in plant development. In this study, we characterized the temperature-sensitive chlorophyll-deficient rice mutant tcd5, which develops albino leaves at low temperatures (20 °C) and normal green leaves at high temperatures (32 °C). The development of chloroplasts and etioplasts is impaired in tcd5 plants at 20 °C, and the temperature-sensitive period for the albino phenotype is the P4 stage of leaf development. The development of thylakoid membranes is arrested at the mid-P4 stage in tcd5 plants at 20 °C. We performed positional cloning of TCD5 and then complementation and knock-down experiments, and the results showed that the transcript LOC_Os05g34040.1 from the LOC_Os05g34040 gene corresponded to the tcd5 phenotype. TCD5 encodes a conserved plastid-targeted monooxygenase family protein which has not been previously reported associated with a temperature-sensitive albino phenotype in plants. TCD5 is abundantly expressed in young leaves and immature spikes, and low temperatures increased this expression. The transcription of some genes involved in plastid transcription/translation and photosynthesis varied in the tcd5 mutant. Although the phenotype and temperature dependence of the TCD5 orthologous mutant phenotype were different in rice and Arabidopsis, OsTCD5 could rescue the phenotype of the Arabidopsis mutant, suggesting that TCD5 function is conserved between monocots and dicots. PMID:27531886

  18. How racial/ethnic bullying affects rejection sensitivity: the role of social dominance orientation.

    PubMed

    Wu, Ivan H C; Lyons, Brent; Leong, Frederick T L

    2015-01-01

    The authors built upon models of workplace bullying to examine how racial/ethnic bullying can lead to racial/ethnic minorities' sensitivity to future discrimination via its effects on race/ethnic-related stress. With a sample of racial/ethnic minorities, they found support for this process. Individual differences in social dominance orientation (SDO) also attenuated the mediation: The indirect effect of race/ethnic-related stress was weaker for minorities who endorse hierarchy legitimizing ideologies (high in SDO) compared to minorities low in SDO. Practical implications for the management of minority employees' experiences of discrimination are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved). PMID:25313428

  19. Central gray modulation of affective defense is differentially sensitive to naloxone.

    PubMed

    Pott, C B; Kramer, S Z; Siegel, A

    1987-01-01

    Specific areas of feline central gray (CG) modulate affective aggression elicited by hypothalamic stimulation and produce analgesia, possibly mediated by enkephalins. Despite correlations between opiates and aggressive behavior suggested previously, their relationship has not been clearly demonstrated. The goal of this study was to examine the possible role of endogenous opiate mechanisms in CG modulation of affective aggression. Electrodes were placed in the ventromedial hypothalamus (VM) which, when stimulated, elicited affective attack. Control latency to VM-elicited hiss was established. CG cannula-electrodes were then implanted. Response modulation was determined by dual stimulation of CG and VM electrodes, alternated with VM stimulation alone. Naloxone was introduced through the CG electrodes and VM-elicited hiss latency was again determined, followed by paired trials of dual and single stimulation. Six ventral facilitatory and eight dorsal inhibitory sites were identified. Naloxone had no effect on CG facilitation but completely blocked CG inhibition of VM-elicited hissing. In support of these findings, it was observed that D-A1A2-MET5-enkephalin injected directly into CG-inhibitory sites suppressed VM-elicited hissing. These results demonstrate that opiate mechanisms are operative in the inhibitory modulation of intra-specific aggression. PMID:3628530

  20. Change in activity of serine palmitoyltransferase affects sensitivity to syringomycin E in yeast Saccharomyces cerevisiae.

    PubMed

    Toume, Moeko; Tani, Motohiro

    2014-09-01

    Syringomycin E is a cyclic lipodepsipeptide produced by strains of the plant bacterium Pseudomonas syringae pv. syringae. Genetic studies involving the yeast Saccharomyces cerevisiae have revealed that complex sphingolipids play important roles in the action of syringomycin E. Here, we found a novel mutation that confers resistance to syringomycin E on yeast; that is, a deletion mutant of ORM1 and ORM2, which encode negative regulators of serine palmitoyltransferase catalyzing the initial step of sphingolipid biosynthesis, exhibited resistance to syringomycin E. On the contrary, overexpression of Orm2 resulted in high sensitivity to the toxin. Moreover, overexpression of Lcb1 and Lcb2, catalytic subunits of serine palmitoyltransferase, causes resistance to the toxin, whereas partial repression of expression of Lcb1 had the opposite effect. Partial reduction of complex sphingolipids by repression of expression of Aur1, an inositol phosphorylceramide synthase, also resulted in high sensitivity to the toxin. These results suggested that an increase in sphingolipid biosynthesis caused by a change in the activity of serine palmitoyltransferase causes resistance to syringomycin E.

  1. Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen

    PubMed Central

    Mendes-Pereira, Ana M.; Sims, David; Dexter, Tim; Fenwick, Kerry; Assiotis, Ioannis; Kozarewa, Iwanka; Mitsopoulos, Costas; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J.; Ashworth, Alan

    2012-01-01

    Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 genes on the cellular response to tamoxifen. This screen, along with subsequent validation experiments, identifies a compendium of genes whose silencing causes tamoxifen resistance (including BAP1, CLPP, GPRC5D, NAE1, NF1, NIPBL, NSD1, RAD21, RARG, SMC3, and UBA3) and also a set of genes whose silencing causes sensitivity to this endocrine agent (C10orf72, C15orf55/NUT, EDF1, ING5, KRAS, NOC3L, PPP1R15B, RRAS2, TMPRSS2, and TPM4). Multiple individual genes, including NF1, a regulator of RAS signaling, also correlate with clinical outcome after tamoxifen treatment. PMID:21482774

  2. Nonassociative learning processes affecting swimming probability in the seaslug Tritonia diomedea: habituation, sensitization and inhibition.

    PubMed

    Brown, G D

    1998-10-01

    The role of nonassociative learning processes in determining whether or not a chemical stimulus will elicit the Tritonia diomedea swimming response was examined in a variety of conditioning experiments. Iterative presentation of a chemical stimulus resulted in a reduced swimming probability (SP). By the criteria of Thompson and Spencer (Thompson RF, Spencer WA. Psychol. Rev. 1966;73:16-43) and others, this iterative reduction of SP was concluded to be the result of habituation. Site-specificity and a below zero effect implicated sensory pathways in habituation memory storage. The iterative reduction in SP was reversible, confirming that a sensitization-like process can also influence SP. It was further concluded that a short-term decrement in swimming cycle number was most likely due to a constraint in the effector pathway. Experience with a tactile stimulus had a long-lasting decremental effect on SP. This heterostimic reduction of SP was amplified in a multistimic paradigm that included both chemical and tactile stimuli during training. The chemical stimuli alone did not alter SP in this experiment. Multistimic reduction lasted for a week and was reversed temporarily by an excitatory chemical stimulus. The long-lasting reduction of SP by tactile stimulation appears to be the result of a novel nonassociative inhibitory process, which was distinguished from other learning processes by its duration and specificity. A total of three distinct learning processes are postulated to account for the role of simple types of experience in determining SP in Tritonia: habituation, sensitization, and nonassociative inhibition.

  3. Head Position in the MEG Helmet Affects the Sensitivity to Anterior Sources

    PubMed Central

    Marinkovic, K; Cox, B; Reid, K; Halgren, E

    2013-01-01

    Current MEG instruments derive the whole-head coverage by utilizing a helmet-shaped opening at the bottom of the dewar. These helmets, however, are quite a bit larger than most people’s heads so subjects commonly lean against the back wall of the helmet in order to maintain a steady position. In such cases the anterior brain sources may be too distant to be picked up by the sensors reliably. Potential “invisibility” of the frontal and anterior temporal sources may be particularly troublesome for the studies of cognition and language, as they are subserved significantly by these areas. We examined the sensitivity of the distributed anatomically-constrained MEG (aMEG) approach to the head position (“front” vs. “back”) secured within a helmet with custom-tailored bite-bars during a lexical decision task. The anterior head position indeed resulted in much greater sensitivity to language-related activity in frontal and anterior temporal locations. These results emphasize the need to adjust the head position in the helmet in order to maximize the “visibility” of the sources in the anterior brain regions in cognitive and language tasks. PMID:16012659

  4. Long-Term Occupational Exposure to Organic Solvents Affects Color Vision, Contrast Sensitivity and Visual Fields

    PubMed Central

    Costa, Thiago Leiros; Barboni, Mirella Telles Salgueiro; Moura, Ana Laura de Araújo; Bonci, Daniela Maria Oliveira; Gualtieri, Mirella; de Lima Silveira, Luiz Carlos; Ventura, Dora Fix

    2012-01-01

    The purpose of this study was to evaluate the visual outcome of chronic occupational exposure to a mixture of organic solvents by measuring color discrimination, achromatic contrast sensitivity and visual fields in a group of gas station workers. We tested 25 workers (20 males) and 25 controls with no history of chronic exposure to solvents (10 males). All participants had normal ophthalmologic exams. Subjects had worked in gas stations on an average of 9.6±6.2 years. Color vision was evaluated with the Lanthony D15d and Cambridge Colour Test (CCT). Visual field assessment consisted of white-on-white 24–2 automatic perimetry (Humphrey II-750i). Contrast sensitivity was measured for sinusoidal gratings of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0 and 20.0 cycles per degree (cpd). Results from both groups were compared using the Mann–Whitney U test. The number of errors in the D15d was higher for workers relative to controls (p<0.01). Their CCT color discrimination thresholds were elevated compared to the control group along the protan, deutan and tritan confusion axes (p<0.01), and their ellipse area and ellipticity were higher (p<0.01). Genetic analysis of subjects with very elevated color discrimination thresholds excluded congenital causes for the visual losses. Automated perimetry thresholds showed elevation in the 9°, 15° and 21° of eccentricity (p<0.01) and in MD and PSD indexes (p<0.01). Contrast sensitivity losses were found for all spatial frequencies measured (p<0.01) except for 0.5 cpd. Significant correlation was found between previous working years and deutan axis thresholds (rho = 0.59; p<0.05), indexes of the Lanthony D15d (rho = 0.52; p<0.05), perimetry results in the fovea (rho = −0.51; p<0.05) and at 3, 9 and 15 degrees of eccentricity (rho = −0.46; p<0.05). Extensive and diffuse visual changes were found, suggesting that specific occupational limits should be created. PMID:22916187

  5. I Feel You: The Design and Evaluation of a Domotic Affect-Sensitive Spoken Conversational Agent

    PubMed Central

    Lutfi, Syaheerah Lebai; Fernández-Martínez, Fernando; Lorenzo-Trueba, Jaime; Barra-Chicote, Roberto; Montero, Juan Manuel

    2013-01-01

    We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction. PMID:23945740

  6. I feel you: the design and evaluation of a domotic affect-sensitive spoken conversational agent.

    PubMed

    Lutfi, Syaheerah Lebai; Fernández-Martínez, Fernando; Lorenzo-Trueba, Jaime; Barra-Chicote, Roberto; Montero, Juan Manuel

    2013-01-01

    We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction. PMID:23945740

  7. I feel you: the design and evaluation of a domotic affect-sensitive spoken conversational agent.

    PubMed

    Lutfi, Syaheerah Lebai; Fernández-Martínez, Fernando; Lorenzo-Trueba, Jaime; Barra-Chicote, Roberto; Montero, Juan Manuel

    2013-08-13

    We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction.

  8. Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions.

    PubMed

    Kashio, Makiko; Sokabe, Takaaki; Shintaku, Kenji; Uematsu, Takayuki; Fukuta, Naomi; Kobayashi, Noritada; Mori, Yasuo; Tominaga, Makoto

    2012-04-24

    The ability to sense temperature is essential for organism survival and efficient metabolism. Body temperatures profoundly affect many physiological functions, including immunity. Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca(2+)-permeable cation channel expressed in a wide range of immunocytes. TRPM2 is activated by adenosine diphosphate ribose and hydrogen peroxide (H(2)O(2)), although the activation mechanism by H(2)O(2) is not well understood. Here we report a unique activation mechanism in which H(2)O(2) lowers the temperature threshold for TRPM2 activation, termed "sensitization," through Met oxidation and adenosine diphosphate ribose production. This sensitization is completely abolished by a single mutation at Met-214, indicating that the temperature threshold of TRPM2 activation is regulated by redox signals that enable channel activity at physiological body temperatures. Loss of TRPM2 attenuates zymosan-evoked macrophage functions, including cytokine release and fever-enhanced phagocytic activity. These findings suggest that redox signals sensitize TRPM2 downstream of NADPH oxidase activity and make TRPM2 active at physiological body temperature, leading to increased cytosolic Ca(2+) concentrations. Our results suggest that TRPM2 sensitization plays important roles in macrophage functions.

  9. Mutants with Altered Sensitivity to a Calmodulin Antagonist Affect the Circadian Clock in Neurospora Crassa

    PubMed Central

    Suzuki, S.; Katagiri, S.; Nakashima, H.

    1996-01-01

    Two newly isolated mutant strains of Neurospora crassa, cpz-1 and cpz-2, were hypersensitive to chlorpromazine with respect to mycelial growth but responded differently to the drug with respect to the circadian conidiation rhythm. In the wild type, chlorpromazine caused shortening of the period length of the conidiation rhythm. Pulse treatment with the drug shifted the phase and inhibited light-induced phase shifting in Neurospora. By contrast to the wild type, the cpz-2 strain was resistant to these inhibitory effects of chlorpromazine. Inhibition of cpz-2 function by chlorpromazine affected three different parameters of circadian conidiation rhythm, namely, period length, phase and light-induced phase shifting. These results indicate that the cpz-2 gene must be involved in or related closely to the clock mechanism of Neurospora. By contrast, the cpz-1 strain was hypersensitive to chlorpromazine with respect to the circadian conidiation rhythm. PMID:8807291

  10. Does body size affect a bird's sensitivity to patch size and landscape structure?

    USGS Publications Warehouse

    Winter, M.; Johnson, D.H.; Shaffer, J.A.

    2006-01-01

    Larger birds are generally more strongly affected by habitat loss and fragmentation than are smaller ones because they require more resources and thus larger habitat patches. Consequently, conservation actions often favor the creation or protection of larger over smaller patches. However, in grassland systems the boundaries between a patch and the surrounding landscape, and thus the perceived size of a patch, can be indistinct. We investigated whether eight grassland bird species with different body sizes perceived variation in patch size and landscape structure in a consistent manner. Data were collected from surveys conducted in 44 patches of northern tallgrass prairie during 1998-2001. The response to patch size was very similar among species regardless of body size (density was little affected by patch size), except in the Greater Prairie-Chicken (Tympanuchus cupido), which showed a threshold effect and was not found in patches smaller than 140 ha. In landscapes containing 0%-30% woody vegetation, smaller species responded more negatively to increases in the percentage of woody vegetation than larger species, but above an apparent threshold of 30%, larger species were not detected. Further analyses revealed that the observed variation in responses to patch size and landscape structure among species was not solely due to body size per se, but to other differences among species. These results indicate that a stringent application of concepts requiring larger habitat patches for larger species appears to limit the number of grassland habitats that can be protected and may not always be the most effective conservation strategy. ?? The Cooper Ornithological Society 2006.

  11. Timing and presence of an attachment person affect sensitivity of aggression tests in shelter dogs.

    PubMed

    Kis, A; Klausz, B; Persa, E; Miklósi, Á; Gácsi, M

    2014-02-22

    Different test series have been developed and used to measure behaviour in shelter dogs in order to reveal individuals not suitable for re-homing due to their aggressive tendencies. However, behavioural tests previously validated on pet dogs seem to have relatively low predictability in the case of shelter dogs. Here, we investigate the potential effects of (1) timing of the behaviour testing and (2) presence of a human companion on dogs' aggressive behaviour. In Study I, shelter dogs (n=25) showed more aggression when tested in a short test series two weeks after they had been placed in the shelter compared to their responses in the same test performed 1-2 days after arrival. In Study II, the occurrence of aggressive behaviour was more probable in pet dogs (n=50) in the presence than in the absence of their passive owner. We conclude that the sensitivity of aggression tests for shelter dogs can be increased by running the test in the presence of a caretaker, and after some period of acclimatisation to the new environment. This methodology could also provide better chances for successful adoption.

  12. Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity

    PubMed Central

    Sakamoto, Shohei; Miyaji, Takaaki; Hiasa, Miki; Ichikawa, Reiko; Uematsu, Akira; Iwatsuki, Ken; Shibata, Atsushi; Uneyama, Hisayuki; Takayanagi, Ryoichi; Yamamoto, Akitsugu; Omote, Hiroshi; Nomura, Masatoshi; Moriyama, Yoshinori

    2014-01-01

    Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut−/−) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut−/− mice. Glucose-responsive ATP release was also absent in pancreatic β-cells in Vnut−/− mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut−/− mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis. PMID:25331291

  13. Timing and presence of an attachment person affect sensitivity of aggression tests in shelter dogs.

    PubMed

    Kis, A; Klausz, B; Persa, E; Miklósi, Á; Gácsi, M

    2014-02-22

    Different test series have been developed and used to measure behaviour in shelter dogs in order to reveal individuals not suitable for re-homing due to their aggressive tendencies. However, behavioural tests previously validated on pet dogs seem to have relatively low predictability in the case of shelter dogs. Here, we investigate the potential effects of (1) timing of the behaviour testing and (2) presence of a human companion on dogs' aggressive behaviour. In Study I, shelter dogs (n=25) showed more aggression when tested in a short test series two weeks after they had been placed in the shelter compared to their responses in the same test performed 1-2 days after arrival. In Study II, the occurrence of aggressive behaviour was more probable in pet dogs (n=50) in the presence than in the absence of their passive owner. We conclude that the sensitivity of aggression tests for shelter dogs can be increased by running the test in the presence of a caretaker, and after some period of acclimatisation to the new environment. This methodology could also provide better chances for successful adoption. PMID:24482210

  14. Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity.

    PubMed

    Sakamoto, Shohei; Miyaji, Takaaki; Hiasa, Miki; Ichikawa, Reiko; Uematsu, Akira; Iwatsuki, Ken; Shibata, Atsushi; Uneyama, Hisayuki; Takayanagi, Ryoichi; Yamamoto, Akitsugu; Omote, Hiroshi; Nomura, Masatoshi; Moriyama, Yoshinori

    2014-10-21

    Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut(-/-)) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut(-/-) mice. Glucose-responsive ATP release was also absent in pancreatic β-cells in Vnut(-/-) mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut(-/-) mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis.

  15. Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress.

    PubMed

    Torres, Mauricio; Castillo, Karen; Armisén, Ricardo; Stutzin, Andrés; Soto, Claudio; Hetz, Claudio

    2010-12-29

    Prion-related disorders (PrDs) are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed PrP(RES). Altered endoplasmic reticulum (ER) homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of PrDs. The ER operates as a major intracellular calcium store, playing a crucial role in pathological events related to neuronal dysfunction and death. Here we investigated the possible impact of PrP misfolding on ER calcium homeostasis in infectious and familial models of PrDs. Neuro2A cells chronically infected with scrapie prions showed decreased ER-calcium content that correlated with a stronger upregulation of UPR-inducible chaperones, and a higher sensitivity to ER stress-induced cell death. Overexpression of the calcium pump SERCA stimulated calcium release and increased the neurotoxicity observed after exposure of cells to brain-derived infectious PrP(RES). Furthermore, expression of PrP mutants that cause hereditary Creutzfeldt-Jakob disease or fatal familial insomnia led to accumulation of PrP(RES) and their partial retention at the ER, associated with a drastic decrease of ER calcium content and higher susceptibility to ER stress. Finally, similar results were observed when a transmembrane form of PrP was expressed, which is proposed as a neurotoxic intermediate. Our results suggest that alterations in calcium homeostasis and increased susceptibility to ER stress are common pathological features of both infectious and familial PrD models.

  16. Gut microbiota affects sensitivity to acute DSS-induced colitis independently of host genotype.

    PubMed

    Brinkman, Brigitta M; Becker, Anne; Ayiseh, Rene B; Hildebrand, Falk; Raes, Jeroen; Huys, Geert; Vandenabeele, Peter

    2013-11-01

    Caspase-deficient mice and wild-type (WT) mice show significant differences in their gut microbiota composition. These differences coincide with the observation that caspase-3-deficient mice carrying a natural caspase-11 mutation (Casp3/11(-/-)) are less sensitive to acute dextran sodium sulfate-induced colitis than WT mice. For these reasons, we investigated the role of the microbiota in the development of colitis by cohousing WT and Casp3/11(-/-) mice. Microbial community fingerprinting by denaturing gradient gel electrophoresis analysis revealed that the similarities in gut microbial composition of WT and Casp3/11(-/-) mice increased after cohousing. In the acute dextran sodium sulfate-induced colitis model, Casp3/11(-/-) mice that were cohoused with WT mice showed increased weight loss and disease activity scores and increased neutrophil infiltration and inflammatory cytokine levels in their colon tissue compared with Casp3/11(-/-) mice that were not cohoused with WT mice. Also, we demonstrate that only the microbiota of the Casp3/11(-/-) mice cohoused with WT mice showed an important increase in Prevotella species. In conclusion, our cohousing experiments revealed that the colitogenic activity of the WT microbiota is transferable to Casp3/11(-/-) mice and that Prevotella species are likely to be involved. By contrast, the relative protection of Casp3/11(-/-) mice against dextran sodium sulfate damage is not transferred to WT mice after cohousing. These results underscore the need for in-depth studies of the bilateral interaction of host genes and microbiota to gain insight into the mechanisms of disease pathogenesis. Our findings also have important implications for the experimental design of disease studies in genetically modified mice and conclusions drawn from them. PMID:24105395

  17. Aggressive experience affects the sensitivity of neurons towards pharmacological treatment in the hypothalamic attack area.

    PubMed

    Haller, J; Abrahám, I; Zelena, D; Juhász, G; Makara, G B; Kruk, M R

    1998-09-01

    Early investigators of brain stimulation-evoked complex behaviours (attack, escape, feeding, self-grooming, sexual behaviour) reported that experience may affect the behavioural outcome of brain stimulation. This intriguing example of functional neuronal plasticity was later totally neglected. The present experiment investigated the behavioural outcome of in vivo microdialysis perfusion of the glutamate agonist kainate and/or the GABAA antagonist bicuculline into the hypothalamic attack area (HAA) of (1) animals naive to dyadic encounters; (2) animals with a recent aggressive experience (the probe being implanted 6-24 h after the last of a series of dyadic encounters); and (3) animals with an earlier aggressive experience (probe being implanted 2 weeks after the last aggressive experience). On the experimental day, rats received two 5-min infusions during a dyadic encounter lasting 35 min with an unknown opponent. Flow rate was 1.5-2 microliters/min, drug concentrations were 1.8 x 10(-5) and 1.5 x 10(-5) M for kainate and bicuculline, respectively. Behaviour was analysed before, during and after perfusions. Only the combined kainate + bicuculline treatment had significant effects on behaviour at the doses studied. A significant increase in aggressive behaviour was elicited only in animals with a recent aggressive experience, while naive animals and with an earlier experience responded to the treatments by grooming. These results appear to support early observations indicating that one important aspect of brain stimulation effects is previous experience. PMID:9832932

  18. Offering a forage crop at pasture did not adversely affect voluntary cow traffic or milking visits in a pasture-based automatic milking system.

    PubMed

    Scott, V E; Kerrisk, K L; Garcia, S C

    2016-03-01

    Feed is a strong incentive for encouraging cows in automatic milking systems (AMS) to voluntarily move around the farm and achieve milkings distributed across the 24 h day. It has been reported that cows show preferences for some forages over others, and it is possible that offering preferred forages may increase cow traffic. A preliminary investigation was conducted to determine the effect of offering a forage crop for grazing on premilking voluntary waiting times in a pasture-based robotic rotary system. Cows were offered one of two treatments (SOYBEAN or GRASS) in a cross-over design. A restricted maximum likelihood procedure was used to model voluntary waiting times. Mean voluntary waiting time was 45.5±6.0 min, with no difference detected between treatments. High and mid-production cows spent 55 min/milking for low-production cows, whereas waiting time increased as queue length increased. Voluntary waiting time was 23% and 80% longer when cows were fetched from the paddock or had a period of forced waiting before volunteering for milking, respectively. The time it took cows to return to the dairy since last exiting was not affected by treatment, with a mean return time of 13.7±0.6 h. Although offering SOYBEAN did not encourage cows to traffic more readily through the premilking yard, the concept of incorporating forage crops in AMS still remains encouraging if the aim is to increase the volume or quantity of home-grown feed rather than improving cow traffic.

  19. Cigarette smoking adversely affects disease activity and disease-specific quality of life in patients with Crohn’s disease at a tertiary referral center

    PubMed Central

    Quezada, Sandra M; Langenberg, Patricia; Cross, Raymond K

    2016-01-01

    Purpose Smoking has a negative impact on disease activity in Crohn’s disease (CD). Smoking may also affect the quality of life, but this has not been evaluated using validated measures over time. We assessed the relationship between smoking and disease-specific quality of life over time in a tertiary referral inflammatory bowel disease cohort. Patients and methods Retrospective cohort study from July 2004 to July 2009 in patients with CD identified from the University of Maryland, Baltimore, Institutional Review Board-approved University of Maryland School of Medicine Inflammatory Bowel Disease Program database. Smoking status was classified as current, former, and never. Age was categorized as <40 years, 40–59 years, and ≥60 years. Index visit disease activity and quality of life was measured with the Harvey–Bradshaw index, and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Repeated measures linear regression was used to assess the association between smoking and quality of life over time after adjustment for confounding variables. Results A total of 608 patients were included, of whom 42% were male; 80% were Caucasian; 22% were current smokers; 24% were former smokers; and 54% were never smokers. Over time, adjusted Harvey–Bradshaw index scores declined in all patients, but current smokers had consistently higher scores. After adjustment for sex, age, and disease duration, never smokers had higher mean SIBDQ scores at index visit compared to former and current smokers (P<0.0001); all increased over time but SIBDQ scores for never smokers remained consistently highest. Conclusion Smoking has a negative impact on disease activity and quality of life in patients with CD. Prospects of improved disease activity and quality of life should be proposed as an additional incentive to encourage smoking cessation in patients with CD. PMID:27703391

  20. Behavioural Responses to Thermal Conditions Affect Seasonal Mass Change in a Heat-Sensitive Northern Ungulate

    PubMed Central

    van Beest, Floris M.; Milner, Jos M.

    2013-01-01

    Background Empirical tests that link temperature-mediated changes in behaviour (activity and resource selection) to individual fitness or condition are currently lacking for endotherms yet may be critical to understanding the effect of climate change on population dynamics. Moose (Alces alces) are thought to suffer from heat stress in all seasons so provide a good biological model to test whether exposure to non-optimal ambient temperatures influence seasonal changes in body mass. Seasonal mass change is an important fitness correlate of large herbivores and affects reproductive success of female moose. Methodology/Principal Findings Using GPS-collared adult female moose from two populations in southern Norway we quantified individual differences in seasonal activity budget and resource selection patterns as a function of seasonal temperatures thought to induce heat stress in moose. Individual body mass was recorded in early and late winter, and autumn to calculate seasonal mass changes (n = 52 over winter, n = 47 over summer). We found large individual differences in temperature-dependent resource selection patterns as well as within and between season variability in thermoregulatory strategies. As expected, individuals using an optimal strategy, selecting young successional forest (foraging habitat) at low ambient temperatures and mature coniferous forest (thermal shelter) during thermally stressful conditions, lost less mass in winter and gained more mass in summer. Conclusions/Significance This study provides evidence that behavioural responses to temperature have important consequences for seasonal mass change in moose living in the south of their distribution in Norway, and may be a contributing factor to recently observed declines in moose demographic performance. Although the mechanisms that underlie the observed temperature mediated habitat-fitness relationship remain to be tested, physiological state and individual variation in thermal tolerance

  1. An eukaryotic translation initiation factor, AteIF5A-2, affects cadmium accumulation and sensitivity in Arabidopsis.

    PubMed

    Xu, Xiao-Yan; Ding, Zhong-Jie; Chen, Lei; Yan, Jin-Ying; Li, Gui-Xin; Zheng, Shao-Jian

    2015-10-01

    Cadmium (Cd) is one of the most toxic elements and can be accumulated in plants easily; meanwhile, eIF5A is a highly conserved protein in all eukaryotic organisms. The present work tried to investigate whether eIF5A is involved in Cd accumulation and sensitivity in Arabidopsis (Arabidopsis thaliana L.) by comparing the wild-type Columbia-0 (Col-0) with a knockdown mutant of AteIF5A-2, fbr12-3 under Cd stress conditions. The results showed that the mutant fbr12-3 accumulated more Cd in roots and shoots and had significantly lower chlorophyll content, shorter root length, and smaller biomass, suggesting that downregulation of AteIF5A-2 makes the mutant more Cd sensitive. Real-time polymerase chain reaction revealed that the expressions of metal transporters involved in Cd uptake and translocation including IRT1, ZIP1, AtNramp3, and AtHMA4 were significantly increased but the expressions of PCS1 and PCS2 related to Cd detoxification were decreased notably in fbr12-3 compared with Col-0. As a result, an increase in MDA and H2 O2 content but decrease in root trolox, glutathione and proline content under Cd stress was observed, indicating that a severer oxidative stress occurs in the mutant. All these results demonstrated for the first time that AteIF5A influences Cd sensitivity by affecting Cd uptake, accumulation, and detoxification in Arabidopsis.

  2. An eukaryotic translation initiation factor, AteIF5A-2, affects cadmium accumulation and sensitivity in Arabidopsis.

    PubMed

    Xu, Xiao-Yan; Ding, Zhong-Jie; Chen, Lei; Yan, Jin-Ying; Li, Gui-Xin; Zheng, Shao-Jian

    2015-10-01

    Cadmium (Cd) is one of the most toxic elements and can be accumulated in plants easily; meanwhile, eIF5A is a highly conserved protein in all eukaryotic organisms. The present work tried to investigate whether eIF5A is involved in Cd accumulation and sensitivity in Arabidopsis (Arabidopsis thaliana L.) by comparing the wild-type Columbia-0 (Col-0) with a knockdown mutant of AteIF5A-2, fbr12-3 under Cd stress conditions. The results showed that the mutant fbr12-3 accumulated more Cd in roots and shoots and had significantly lower chlorophyll content, shorter root length, and smaller biomass, suggesting that downregulation of AteIF5A-2 makes the mutant more Cd sensitive. Real-time polymerase chain reaction revealed that the expressions of metal transporters involved in Cd uptake and translocation including IRT1, ZIP1, AtNramp3, and AtHMA4 were significantly increased but the expressions of PCS1 and PCS2 related to Cd detoxification were decreased notably in fbr12-3 compared with Col-0. As a result, an increase in MDA and H2 O2 content but decrease in root trolox, glutathione and proline content under Cd stress was observed, indicating that a severer oxidative stress occurs in the mutant. All these results demonstrated for the first time that AteIF5A influences Cd sensitivity by affecting Cd uptake, accumulation, and detoxification in Arabidopsis. PMID:25559189

  3. The increased sensitivity of human cytomegalovirus (HCMV) PCR quantitation in whole blood affects reproductive rate (Ro) measurement.

    PubMed

    Gurtler, Volker; Mayall, Barrie C; Wang, Jenny; Ghaly-Derias, Shahbano

    2014-02-01

    In order to determine the effect of the increase in sensitivity of HCMV detection in whole blood compared to plasma on reproductive rate (Ro) measurement, an optimized human cytomegalovirus (HCMV) quantitative PCR assay was developed. The results presented in this study are summarized by the following three methodological improvements: (i) at values below the limit of quantitation (LOQ) of 60copies/ml, determination of HCMV load was more sensitive with whole blood than plasma, (ii) for the determination of viral load, whole blood was more sensitive than plasma below 1000copies/ml but little difference was observed above 1000copies/ml and (iii) the measurement of "Reproductive Rate" can be affected by imprecise measurement of HCMV viral load in either plasma or whole blood compartments depending on whether samples were taken from patients on antiviral treatment or from patients where HCMV load was rising. Taken together this study provides methodological improvements suggesting that below HCMV viral load levels of 1000copies/ml (1640IU/ml) both plasma and whole blood should be tested.

  4. Lactose in milk replacer can partly be replaced by glucose, fructose, or glycerol without affecting insulin sensitivity in veal calves.

    PubMed

    Pantophlet, A J; Gilbert, M S; van den Borne, J J G C; Gerrits, W J J; Roelofsen, H; Priebe, M G; Vonk, R J

    2016-04-01

    Calf milk replacer (MR) contains 40 to 50% lactose. Lactose strongly fluctuates in price and alternatives are desired. Also, problems with glucose homeostasis and insulin sensitivity (i.e., high incidence of hyperglycemia and hyperinsulinemia) have been described for heavy veal calves (body weight >100 kg). Replacement of lactose by other dietary substrates can be economically attractive, and may also positively (or negatively) affect the risk of developing problems with glucose metabolism. An experiment was designed to study the effects of replacing one third of the dietary lactose by glucose, fructose, or glycerol on glucose homeostasis and insulin sensitivity in veal calves. Forty male Holstein-Friesian (body weight=114 ± 2.4 kg; age=97 ± 1.4 d) calves were fed an MR containing 462 g of lactose/kg (CON), or an MR in which 150 g of lactose/kg of MR was replaced by glucose (GLU), fructose (FRU), or glycerol (GLY). During the first 10d of the trial, all calves received CON. The CON group remained on this diet and the other groups received their experimental diets for a period of 8 wk. Measurements were conducted during the first (baseline) and last week of the trial. A frequently sampled intravenous glucose tolerance test was performed to assess insulin sensitivity and 24 h of urine was collected to measure glucose excretion. During the last week of the trial, a bolus of 1.5 g of [U-(13)C] substrates was added to their respective meals and plasma glucose, insulin, and (13)C-glucose responses were measured. Insulin sensitivity was low at the start of the trial and remained low [1.2 ± 0.1 and 1.0 ± 0.1 (mU/L)(-1) × min(-1)], and no treatment effect was noted. Glucose excretion was low at the start of the trial (3.4 ± 1.0 g/d), but increased in CON and GLU calves (26.9 ± 3.9 and 43.0 ± 10.6g/d) but not in FRU and GLY calves. Postprandial glucose was higher in GLU, lower in FRU, and similar in GLY compared with CON calves. Postprandial insulin was lower in FRU

  5. Simulated microgravity affects semicarbazide-sensitive amine oxidase expression in recombinant Escherichia coli by HPLC-ESI-QQQ analysis.

    PubMed

    Zhang, Yongqian; Lai, Chengjun; Duan, Jinyan; Guan, Ningxin; Ullah, Kaleem; Deng, Yulin

    2012-05-01

    Simulated microgravity has been reported to affect the gene, protein expression, and its function in the cells. Semicarbazide-sensitive amine oxidase (SSAO; E.C.1.4.3.6.) is widely distributed in vascular cells, smooth muscle cells, and adipocytes. It is noteworthy whether the expression of SSAO is affected under simulated microgravity or not. In this study, an SSAO-transformed Escherichia coli BL21 was constructed firstly. Then, a sensitive, selective, and accurate method based on high-performance liquid chromatography electrospray ionization triple quadrupole (HPLC-ESI-QQQ) was developed to determine the amount of SSAO in the E. coli BL21. The limit of detection and limit of quantification were 5.0 and 10 fmol, respectively. Finally, SSAO expression in the recombinant E. coli BL21 was evaluated with various gravity and temperature conditions by HPLC-ESI-QQQ analysis. It is interesting that the tendency in the alteration of SSAO under simulated microgravity showed temperature difference. At 18 °C, the amount of SSAO in the inclusion bodies and soluble fractions under the simulated microgravity increased by 83% and 116%, respectively, compared with normal gravity. However, the decrease by 38% and 49% in the inclusion bodies and soluble fractions under the simulated microgravity was observed at 37 °C. Results obtained here indicate that the SSAO expression under simulated microgravity is dramatically sensitive to the temperature. On the other hand, a novel bioreactor from this study may also be useful for the recombinant protein expression in the field of gene engineering.

  6. Adverse effects of anabolic steroids.

    PubMed

    Hickson, R C; Ball, K L; Falduto, M T

    1989-01-01

    Anabolic steroids are used therapeutically for various disorders and as ergogenic aids by athletes to augment strength, muscular development, and to enhance performance. There is a wide range of concomitant temporary and permanent adverse effects with steroid administration. Several well-documented adverse actions of these hormones may develop rapidly within several weeks or less (i.e. altered reproductive function) or require up to several years of steroid intake (i.e. liver carcinoma). More recent studies indicate that glucose intolerance, insulin resistance, increased cardiovascular disease risk profiles, cerebral dangers, musculoskeletal injuries, prostate cancer, psychosis and schizophrenic episodes, among others, accompany anabolic steroid intake. There is, at present, no evidence to support the claim that athletes are less susceptible to adverse effects than those individuals receiving hormone treatment in a clinical setting. Based on the available information which has accumulated primarily from cross-sectional, short term longitudinal, and case studies, there is a need: (a) to develop a comprehensive battery of specific and sensitive markers of adverse effects, particularly those that would be able to detect the onset of adverse actions; and (b) to conduct controlled long term longitudinal studies in order to fully understand the extensiveness and mechanisms involved in the occurrence of adverse effects.

  7. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  8. Sirtuin Inhibition Adversely Affects Porcine Oocyte Meiosis

    PubMed Central

    Zhang, Liang; Ma, Rujun; Hu, Jin; Ding, Xiaolin; Xu, Yinxue

    2015-01-01

    Sirtuins have been implicated in diverse biological processes, including oxidative stress, energy metabolism, cell migration, and aging. Here, we employed Sirtuin inhibitors, nicotinamide (NAM) and Sirtinol, to investigate their effects on porcine oocyte maturation respectively. The rate of polar body extrusion in porcine oocytes decreased after treatment with NAM and Sirtinol, accompanied with the failure of cumulus cell expansion. We further found that NAM and Sirtinol significantly disrupted oocyte polarity, and inhibited the formation of actin cap and cortical granule-free domain (CGFD). Moreover, the abnormal spindles and misaligned chromosomes were readily detected during porcine oocyte maturation after treatment with NAM and Sirtinol. Together, these results suggest that Sirtuins are involved in cortical polarity and spindle organization in porcine oocytes. PMID:26176547

  9. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    SciTech Connect

    Chen, Y.-J.; Liao, H.-F.; Tsai, T.-H.; Wang, S.-Y.; Shiao, M.-S. . E-mail: msshiao@vghtpe.gov.tw

    2005-11-15

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.

  10. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  11. Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice

    PubMed Central

    Yu, Qinghui; Teixeira, Cátia M.; Mahadevia, Darshini; Huang, Yung-Yu; Balsam, Daniel; Mann, J John; Gingrich, Jay A; Ansorge, Mark S.

    2014-01-01

    Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypo-activity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (> P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction. PMID:24589889

  12. Egg intensity and freeze-thawing of fecal samples affect sensitivity of Echinococcus multilocularis detection by PCR.

    PubMed

    Klein, C; Liccioli, S; Massolo, A

    2014-10-01

    Echinococcus multilocularis is one of the most relevant zoonotic parasites with about 18,000 human cases per year. Its detection in wild host is crucial for disease prevention. The present study aimed to determine factors affecting the sensitivity of E. multilocularis detection by PCR using DNA extracted from fecal samples of coyotes (Canis latrans). Fecal samples were screened for the presence of Taeniidae eggs through centrifugation and sedimentation. DNA was extracted from fecal samples with and without prior freeze-thawing of the sample and then subjected to PCR targeting a mitochondrial gene (nad1) and a multi-loci microsatellite marker (EmsB). The presence of PCR inhibitors was determined through internal amplification control. Subjecting the sample to repeated freeze-thaw cycles significantly increased the sensitivity of the PCR by 20%. Likewise, egg intensity had a significant effect on PCR, an effect which was more pronounced for samples not subjected to freeze-thawing. Two or more eggs per gram of feces significantly increased the odds for a positive PCR outcome. The presence of PCR inhibitors had no effect on PCR in samples subjected to freeze-thaw cycles, whereas in samples not subjected to freeze-thaw cycles, the presence of PCR inhibitors was associated with a 0.78 lower odds ratio of positive PCR outcome. Targeting a nuclear versus a mitochondrial gene did not have a significant effect on the sensitivity of PCR. We recommend freeze-thawing samples prior to DNA extraction to become a standard procedure for E. multilocularis detection in canid feces. PMID:25082017

  13. Factors affecting the sensitivity and detection limits of MRI, CT, and SPECT for multimodal diagnostic and therapeutic agents.

    PubMed

    Seevinck, Peter R; Seppenwoolde, Jan-Henry; de Wit, Tim C; Nijsen, Johannes F W; Beekman, Freek J; van Het Schip, Alfred D; Bakker, Chris J G

    2007-05-01

    Noninvasive imaging techniques like magnetic resonance imaging (MRI), computed tomography (CT) and single photon emission computed tomography (SPECT) play an increasingly important role in the diagnostic workup and treatment of cancerous disease. In this context, a distinct trend can be observed towards the development of contrast agents and radiopharmaceuticals that open up perspectives on a multimodality imaging approach, involving all three aforementioned techniques. To promote insight into the potentialities of such an approach, we prepared an overview of the strengths and limitations of the various imaging techniques, in particular with regard to their capability to quantify the spatial distribution of a multimodal diagnostic agent. To accomplish this task, we used a two-step approach. In the first step, we examined the situation for a particular therapeutic anti-cancer agent with multimodal imaging opportunities, viz. holmium-loaded microspheres (HoMS). Physical phantom experiments were performed to enable a comparative evaluation of the three modalities assuming the use of standard equipment, standard clinical scan protocols, and signal-known-exactly conditions. These phantom data were then analyzed so as to obtain first order estimates of the sensitivity and detection limits of MRI, CT and SPECT for HoMS. In the second step, the results for HoMS were taken as a starting point for a discussion of the factors affecting the sensitivity and detection limits of MRI, CT and SPECT for multimodal agents in general. In this, emphasis was put on the factors that must be taken into account when extrapolating the findings for HoMS to other diagnostic tasks, other contrast agents, other experimental conditions, and other scan protocols.

  14. The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity.

    PubMed

    Kubaszek, Agata; Pihlajamäki, Jussi; Punnonen, Kari; Karhapää, Pauli; Vauhkonen, Ilkka; Laakso, Markku

    2003-02-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in many tissues. IL-6 null mice show low energy expenditure, but the effect of the variants of the IL-6 gene on energy expenditure has not been previously studied in humans. Therefore, we investigated the effect of the C-174G promoter polymorphism of the IL-6 gene on energy expenditure, measured by indirect calorimetry in healthy Finnish subjects (n = 124). We also measured insulin sensitivity by the hyperinsulinemic-euglycemic clamp. Subjects with the C-174C genotype of the IL-6 gene had significantly lower energy expenditure than subjects with the G-174C or G-174G genotypes both in fasting (CC 13.68 +/- 1.98, CG 14.73 +/- 1.57, GG 14.81 +/- 2.01 kcal x kg(-1) x min(-1); P = 0.012) and during the euglycemic-hyperinsulinemic clamp (CC 15.24 +/- 2.05, CG 16.62 +/- 2.06, GG 16.66 +/- 2.50 kcal x kg(-1) x min(-1); P = 0.007). Moreover, subjects homozygous for the C allele had lower rates of whole-body glucose uptake than carriers of the G allele (CC 50.95 +/- 13.91, CG 59.40 +/- 14.17, GG 59.21 +/- 15.93 micro mol x kg(-1) x min(-1); P = 0.016). The rates of both oxidative (P = 0.013) and nonoxidative (P = 0.016) glucose disposal were significantly affected by the IL-6 promoter polymorphism. In conclusion, the C-174C promoter polymorphism of the IL-6 gene influences energy expenditure and insulin sensitivity in healthy normoglycemic subjects. Whether this polymorphism is a risk factor for obesity or type 2 diabetes can be estimated only in prospective population-based studies.

  15. Aboveground allometric models for freeze-affected black mangroves (Avicennia germinans): equations for a climate sensitive mangrove-marsh ecotone

    USGS Publications Warehouse

    Osland, Michael J.; Day, Richard H.; Larriviere, Jack C.; From, Andrew S.

    2014-01-01

    Across the globe, species distributions are changing in response to climate change and land use change. In parts of the southeastern United States, climate change is expected to result in the poleward range expansion of black mangroves (Avicennia germinans) at the expense of some salt marsh vegetation. The morphology of A. germinans at its northern range limit is more shrub-like than in tropical climes in part due to the aboveground structural damage and vigorous multi-stem regrowth triggered by extreme winter temperatures. In this study, we developed aboveground allometric equations for freeze-affected black mangroves which can be used to quantify: (1) total aboveground biomass; (2) leaf biomass; (3) stem plus branch biomass; and (4) leaf area. Plant volume (i.e., a combination of crown area and plant height) was selected as the optimal predictor of the four response variables. We expect that our simple measurements and equations can be adapted for use in other mangrove ecosystems located in abiotic settings that result in mangrove individuals with dwarf or shrub-like morphologies including oligotrophic and arid environments. Many important ecological functions and services are affected by changes in coastal wetland plant community structure and productivity including carbon storage, nutrient cycling, coastal protection, recreation, fish and avian habitat, and ecosystem response to sea level rise and extreme climatic events. Coastal scientists in the southeastern United States can use the identified allometric equations, in combination with easily obtained and non-destructive plant volume measurements, to better quantify and monitor ecological change within the dynamic, climate sensitive, and highly-productive mangrove-marsh ecotone.

  16. Aboveground Allometric Models for Freeze-Affected Black Mangroves (Avicennia germinans): Equations for a Climate Sensitive Mangrove-Marsh Ecotone

    PubMed Central

    Osland, Michael J.; Day, Richard H.; Larriviere, Jack C.; From, Andrew S.

    2014-01-01

    Across the globe, species distributions are changing in response to climate change and land use change. In parts of the southeastern United States, climate change is expected to result in the poleward range expansion of black mangroves (Avicennia germinans) at the expense of some salt marsh vegetation. The morphology of A. germinans at its northern range limit is more shrub-like than in tropical climes in part due to the aboveground structural damage and vigorous multi-stem regrowth triggered by extreme winter temperatures. In this study, we developed aboveground allometric equations for freeze-affected black mangroves which can be used to quantify: (1) total aboveground biomass; (2) leaf biomass; (3) stem plus branch biomass; and (4) leaf area. Plant volume (i.e., a combination of crown area and plant height) was selected as the optimal predictor of the four response variables. We expect that our simple measurements and equations can be adapted for use in other mangrove ecosystems located in abiotic settings that result in mangrove individuals with dwarf or shrub-like morphologies including oligotrophic and arid environments. Many important ecological functions and services are affected by changes in coastal wetland plant community structure and productivity including carbon storage, nutrient cycling, coastal protection, recreation, fish and avian habitat, and ecosystem response to sea level rise and extreme climatic events. Coastal scientists in the southeastern United States can use the identified allometric equations, in combination with easily obtained and non-destructive plant volume measurements, to better quantify and monitor ecological change within the dynamic, climate sensitive, and highly-productive mangrove-marsh ecotone. PMID:24971938

  17. B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

    PubMed

    Dunussi-Joannopoulos, Kyri; Hancock, Gerald E; Kunz, Arthur; Hegen, Martin; Zhou, Xiaochuan X; Sheppard, Barbara J; Lamothe, Jennifer; Li, Evelyn; Ma, Hak-Ling; Hamann, Philip R; Damle, Nitin K; Collins, Mary

    2005-10-01

    We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

  18. The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs.

    PubMed

    Visconti, R; Della Monica, R; Palazzo, L; D'Alessio, F; Raia, M; Improta, S; Villa, M R; Del Vecchio, L; Grieco, D

    2015-09-01

    To grant faithful chromosome segregation, the spindle assembly checkpoint (SAC) delays mitosis exit until mitotic spindle assembly. An exceedingly prolonged mitosis, however, promotes cell death and by this means antimicrotubule cancer drugs (AMCDs), that impair spindle assembly, are believed to kill cancer cells. Despite malformed spindles, cancer cells can, however, slip through SAC, exit mitosis prematurely and resist killing. We show here that the Fcp1 phosphatase and Wee1, the cyclin B-dependent kinase (cdk) 1 inhibitory kinase, play a role for this slippage/resistance mechanism. During AMCD-induced prolonged mitosis, Fcp1-dependent Wee1 reactivation lowered cdk1 activity, weakening SAC-dependent mitotic arrest and leading to mitosis exit and survival. Conversely, genetic or chemical Wee1 inhibition strengthened the SAC, further extended mitosis, reduced antiapoptotic protein Mcl-1 to a minimum and potentiated killing in several, AMCD-treated cancer cell lines and primary human adult lymphoblastic leukemia cells. Thus, the Fcp1-Wee1-Cdk1 (FWC) axis affects SAC robustness and AMCDs sensitivity. PMID:25744022

  19. Differences in the sensitivity of fungi and bacteria to season and invertebrates affect leaf litter decomposition in a Mediterranean stream.

    PubMed

    Mora-Gómez, Juanita; Elosegi, Arturo; Duarte, Sofia; Cássio, Fernanda; Pascoal, Cláudia; Romaní, Anna M

    2016-08-01

    Microorganisms are key drivers of leaf litter decomposition; however, the mechanisms underlying the dynamics of different microbial groups are poorly understood. We investigated the effects of seasonal variation and invertebrates on fungal and bacterial dynamics, and on leaf litter decomposition. We followed the decomposition of Populus nigra litter in a Mediterranean stream through an annual cycle, using fine and coarse mesh bags. Irrespective of the season, microbial decomposition followed two stages. Initially, bacterial contribution to total microbial biomass was higher compared to later stages, and it was related to disaccharide and lignin degradation; in a later stage, bacteria were less important and were associated with hemicellulose and cellulose degradation, while fungi were related to lignin decomposition. The relevance of microbial groups in decomposition differed among seasons: fungi were more important in spring, whereas in summer, water quality changes seemed to favour bacteria and slowed down lignin and hemicellulose degradation. Invertebrates influenced litter-associated microbial assemblages (especially bacteria), stimulated enzyme efficiencies and reduced fungal biomass. We conclude that bacterial and fungal assemblages play distinctive roles in microbial decomposition and differ in their sensitivity to environmental changes, ultimately affecting litter decomposition, which might be particularly relevant in highly seasonal ecosystems, such as intermittent streams.

  20. The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs.

    PubMed

    Visconti, R; Della Monica, R; Palazzo, L; D'Alessio, F; Raia, M; Improta, S; Villa, M R; Del Vecchio, L; Grieco, D

    2015-09-01

    To grant faithful chromosome segregation, the spindle assembly checkpoint (SAC) delays mitosis exit until mitotic spindle assembly. An exceedingly prolonged mitosis, however, promotes cell death and by this means antimicrotubule cancer drugs (AMCDs), that impair spindle assembly, are believed to kill cancer cells. Despite malformed spindles, cancer cells can, however, slip through SAC, exit mitosis prematurely and resist killing. We show here that the Fcp1 phosphatase and Wee1, the cyclin B-dependent kinase (cdk) 1 inhibitory kinase, play a role for this slippage/resistance mechanism. During AMCD-induced prolonged mitosis, Fcp1-dependent Wee1 reactivation lowered cdk1 activity, weakening SAC-dependent mitotic arrest and leading to mitosis exit and survival. Conversely, genetic or chemical Wee1 inhibition strengthened the SAC, further extended mitosis, reduced antiapoptotic protein Mcl-1 to a minimum and potentiated killing in several, AMCD-treated cancer cell lines and primary human adult lymphoblastic leukemia cells. Thus, the Fcp1-Wee1-Cdk1 (FWC) axis affects SAC robustness and AMCDs sensitivity.

  1. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues.

    PubMed

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-12-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/-) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.

  2. Pharmacogenomics of adverse drug reactions

    PubMed Central

    2013-01-01

    Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed. PMID:23360680

  3. Myocardial performance index is sensitive to changes in cardiac contractility, but is also affected by vascular load condition.

    PubMed

    Uemura, Kazunori; Kawada, Toru; Zheng, Can; Li, Meihua; Shishido, Toshiaki; Sugimachi, Masaru

    2013-01-01

    Myocardial performance index (MPI), or Tei index, is measured by Doppler echocardiography in clinical practice. MPI has been shown to be useful in evaluating left ventricular (LV) performance and predicting prognosis in cardiac patients. However, the effects of LV load and contractile states on MPI remain to be thoroughly investigated. In 14 anesthetized dogs, we obtained LV pressure-volume relationship with use of sonomicrometry and catheter-tip manometry. MPI was determined from the time derivative of LV volume and pressure. LV end-systolic pressure-volume ratio (Ees'), effective arterial elastance (Ea) and LV end-diastolic volume (Ved) were used as indices of LV contractility, afterload and preload, respectively. Hemodynamic conditions were varied over wide ranges [heart rate (HR), 66-192 bpm; mean arterial pressure, 71-177 mmHg] by infusing cardiovascular agents, by inducing ischemic heart failure and by electrical atrial pacing. Multiple linear regression analysis of pooled data (66 data sets) indicated that MPI (0.6-1.8) significantly correlated with Ees' [1.5-17.5 mmHg · ml(-1), p<0.0001, standard partial regression coefficient (β) =-0.66], Ea (3.6-21.9 mmHg · ml(-1), p<0.001, β = 0.4) and Ved (11-100 ml, p<0.0001, β = -0.69). MPI directly correlated with the time constant of isovolumic relaxation (19-66 ms, p<0.05), but not with HR or LV diastolic-stiffness (all p>0.1). Theoretical analysis also indicated that MPI decreases following the increases in LV contractility and in preload, while it increases in response to an increase in LV afterload. We conclude that MPI sensitively detects changes in LV contractility. However, MPI is also affected by changes in LV afterload and preload. PMID:24109782

  4. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  5. The Effects of T-Group Training and Group Video Recall Procedures on Affective Sensitivity, Openmindedness and Self-Perception Change in Counselors.

    ERIC Educational Resources Information Center

    Cerra, Patrick Frank

    This study investigated the relative effect of T group training and Group Video Recall (GVR) procedures in the growth of affective sensitivity, openmindedness, and self-perception in 17 Indiana University students majoring or minoring in Counseling and Guidance. Relationships among the three behaviors were also sought. The Rokeach Dogmatism Scale…

  6. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  7. Maternal respiratory sensitization and gestational allergen exposure does not affect subsequent pup responses to homologous or heterologous allergen.

    PubMed

    Pucheu-Haston, Cherie M; Copeland, Lisa B; Haykal-Coates, Najwa; Ward, Marsha D W

    2010-03-01

    Evidence suggests that the predisposition towards atopy begins early in life. Maternal allergy has been associated with an increased risk of the development of allergic disease in offspring. Some studies suggest that the development of childhood atopy may also be influenced by prenatal allergen exposure. In this study, a respiratory allergen exposure model was used to determine the impact of maternal sensitization (with or without additional exposures during pregnancy) on subsequent pup responses to homologous or heterologous allergen. Female BALB/c mice received two intratracheal aspiration (IA) exposures to Metarhizium anisopliae crude antigen (MACA) or Hank's buffered salt solution (HBSS) prior to breeding. Some mice also received three additional exposures during pregnancy. Control mothers did not receive treatment. Young adult offspring received three IA exposures to MACA, house dust mite extract (HDM) or HBSS. Offspring sensitized as young adults to either HDM or MACA developed an airway inflammatory response, including increased bronchoalveolar lavage fluid lactate dehydrogenase activity, total protein and total and differential cell counts compared to offspring exposed to HBSS. Increased airway responsiveness to methacholine was observed in pups treated with HDM but not with MACA. Maternal sensitization status (with or without gestational allergen exposure) had no effect on offspring response to either MACA or HDM. In conclusion, this study demonstrates that IA administration of MACA or HDM extract to young adult BALB/c mice induces the development of an inflammatory airway response. In contrast to previous reports, neither maternal sensitization nor gestational allergen exposure could be demonstrated to have a clear effect on offspring sensitization. This discrepancy may be a function of the respiratory sensitization and exposure protocol used in this study, which mimics natural sensitization more closely than do parenteral routes of exposure. PMID

  8. Assessment of toxicity thresholds in aquatic environments: does benthic growth of diatoms affect their exposure and sensitivity to herbicides?

    PubMed

    Larras, Floriane; Montuelle, Bernard; Bouchez, Agnès

    2013-10-01

    Benthic diatoms evolved in a biofilm structure, at the interface between water and substrata. Biofilms can adsorb toxicants, such as herbicides, but little is known about the exposure of biofilm organisms, such as benthic diatoms, to these adsorbed herbicides. We assessed the sensitivity of 11 benthic diatoms species to 6 herbicides under both planktonic and benthic conditions using single-species bioassays. The concentration that reduced the growth rate of the population by 10% (EC10) and 50% (EC50), respectively, varied depending on the species, the herbicides, and the growth forms involved. As a general trend, the more hydrophobic the herbicide, the more species were found to be sensitive under benthic growth conditions. Statistical differences (alpha<5%) were observed between the sensitivities under planktonic and benthic growth conditions for many hydrophobic herbicides. A protective effect of the biofilm against herbicides was observed, and this tended to decrease (at both the EC10 and EC50 levels) with increasing hydrophobicity. The biofilm matrix appeared to control exposure to herbicides, and consequently their toxicity towards benthic diatoms. For metolachlor, terbutryn and irgarol, benthic thresholds derived from species sensitivity distributions were more protective than planktonic thresholds. For hydrophobic herbicides, deriving sensitivity thresholds from data obtained under benthic growth seems to offer a promising alternative.

  9. Neural correlates of automatic perceptual sensitivity to facial affect in posttraumatic stress disorder subjects who survived L'Aquila eartquake of April 6, 2009.

    PubMed

    Mazza, Monica; Catalucci, Alessia; Mariano, Melania; Pino, Maria Chiara; Tripaldi, Simona; Roncone, Rita; Gallucci, Massimo

    2012-09-01

    The "Emotional Numbing" (EN) constitutes one of the core symptoms in PTSD although its exact nature remains elusive. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. The aim of our study, which included ten physically healthy subjects with PTSD, diagnosed according to DSM-IV-TR, who survived L'Aquila earthquake of April 6, 2009, and 10 healthy controls matching for age, sex and education, was to examine automatic perceptual sensitivity to facial affect in PTSD, through an affective priming task that was administered during functional magnetic resonance (fMRI). Behavioural data revealed in the PTSD group a higher sensitivity to negative facial affect on an automatic processing level. FMRI data analysis revealed that PTSD subjects showed a significantly higher activation in right insula and left amygdala that we did not observe in healthy subjects; on the contrary, healthy controls showed a greater activation of left lingual gyrus. Our data support the hypothesis that PTSD appears to be sensitive to negative affect on an automatic processing level and correlates with the activation of specific areas involved in processing emotions. An elevated activation of these areas may underlie the emotion dysregulation in PTSD and could explain the Emotional Numbing symptom associated with this disorder. The present study suffers of a number of limitations, for instance, the relatively small sample size did not allow the application of alternative statistical models.

  10. Partial inactivation of nucleus accumbens core decreases delay discounting in rats without affecting sensitivity to delay or magnitude.

    PubMed

    Moschak, Travis M; Mitchell, Suzanne H

    2014-07-15

    Increased preference for smaller, sooner rewards (delay discounting) is associated with several behavioral disorders, including ADHD and substance use disorders. However, delay discounting is a complex cognitive process and the relationship is unclear between the pathophysiology of the disorders and the component processes underlying delay discounting, including sensitivity to reinforcer delay and sensitivity to reinforcer magnitude. To investigate these processes, male Long Evans rats were trained in one of three tasks measuring sensitivity to delay, sensitivity to magnitude, or both (typical delay discounting task). After learning the task, animals were implanted with bilateral cannulae into either the nucleus accumbens core (AcbC) or the lateral orbitofrontal cortex (lOFC), both of which have been implicated in delay discounting. Upon recovering from the surgery, a baclofen/muscimol cocktail was infused to temporarily inactivate each of these two regions and task performance was assessed. Unlike previous studies showing that lesions of the AcbC increased delay discounting, partial inactivation of the AcbC decreased delay discounting, although it had no effects on the tasks independently assessing either sensitivity to delay or magnitude. The effects of AcbC inactivation were larger in animals that had low levels of delay discounting at baseline. Inactivation of the lOFC had no effects on behavior in any task. These findings suggest that the AcbC may act to promote impulsive choice in individuals with low impulsivity. Furthermore, the data suggest that the AcbC is able to modulate delay and magnitude sensitivity together, but not either of the two in isolation.

  11. Assessment of Relationship-Specific Incentive and Threat Sensitivities: Predicting Satisfaction and Affect in Adult Intimate Relationships

    ERIC Educational Resources Information Center

    Laurenceau, Jean-Philippe; Kleinman, Brighid M.; Kaczynski, Karen J.; Carver, Charles S.

    2010-01-01

    Self-report scales assessing relationship-specific incentive and threat sensitivity were created. Initial tests of factor structure and associations with relationship quality were conducted in a sample of persons in intimate relationships (Study 1). Associations with conceptually related measures were examined to determine convergent and…

  12. X-ray survival characteristics and genetic analysis for nineSaccharomyces deletion mutants that affect radiation sensitivity

    SciTech Connect

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2006-07-21

    We examine ionizing radiation (IR) sensitivity and epistasisrelationships of several Saccharomyces mutants affectingpost-translational modifications of histones H2B and H3. Mutantsbre1delta, lge1delta, and rtf1delta, defective in histone H2B lysine 123ubiquitination, show IR sensitivity equivalent to that of the dot1deltamutant that we reported on earlier, consistent with published findingsthat Dot1p requires H2B K123 ubiquitination to fully methylate histone H3K79. This implicates progressive K79 methylation rather thanmono-methylation in IR resistance. The set2delta mutant, defective in H3K36 methylation, shows mild IR sensitivity whereas mutants that abolishH3 K4 methylation resemble wild type. The dot1delta, bre1delta, andlge1delta mutants show epistasis for IR sensitivity. The paf1deltamutant, also reportedly defective in H2B K123 ubiquitination, confers nosensitivity. The rad6delta, rad51null, rad50delta, and rad9deltamutations are epistatic to bre1? and dot1delta, but rad18delta andrad5delta show additivity with bre1delta, dot1delta, and each other. Thebre1delta rad18delta double mutant resembles rad6delta in sensitivity;thus the role of Rad6p in ubiquitinating H2B accounts for its extrasensitivity compared to rad18delta. We conclude that IR resistanceconferred by BRE1 and DOT1 is mediated through homologous recombinationalrepair, not postreplication repair, and confirm findings of a G1checkpoint role for the RAD6/BRE1/DOT1 pathway.

  13. Adverse reactions to cosmetics.

    PubMed

    Gendler, E

    1987-06-01

    Adverse reactions to cosmetics can be irritant or allergic and are most often caused by fragrances or preservatives. Preservatives include formaldehyde, formaldehyde releasers, and parabens. Other agents that cause allergy are paraphenylenediamine in hair dyes and toluene sulfonamide formaldehyde resin in nail polishes.

  14. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  15. The association of dehydroepiandrosterone and dehydroepiandrosterone sulfate with anxiety sensitivity and electronic diary negative affect among smokers with and without posttraumatic stress disorder.

    PubMed

    Van Voorhees, Elizabeth E; Dennis, Michelle F; McClernon, F Joseph; Calhoun, Patrick S; Buse, Natalie A; Beckham, Jean C

    2013-08-01

    Posttraumatic stress disorder (PTSD) is associated with increased smoking initiation, maintenance, and relapse. Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are neurosteroids that have been associated with mood measures as well as smoking status, and nicotine is associated with increased DHEA and DHEAS levels. Given the difficulties with mood experienced by smokers with PTSD, the purpose of the current study was to evaluate the association between negative affect and anxiety sensitivity with DHEA and DHEAS levels. Ninety-six smokers with and without PTSD provided blood samples for neurosteroid analyses and completed self-report measures of anxiety sensitivity and electronic diary ratings of negative affect. As expected, PTSD smokers reported higher levels of anxiety sensitivity (F(1,94) = 20.67, partial η2 = 0.18, P < 0.0001) and negative affect (F(1,91) = 7.98, partial η2 = 0.08, P = 0.006). After accounting for age and sex, DHEAS was significantly inversely associated with both anxiety sensitivity (F(3,92) = 6.97, partial η2 = 0.07, P = 0.01) and negative affect (F(3,87) = 10.52, partial η2 = 0.11, P = 0.002) across groups. Effect sizes indicated that these effects are moderate to high. No significant interactions of diagnosis and DHEA(S) levels with mood measures were detected. Given that nicotine is known to elevate DHEA(S) levels, these results suggest that DHEAS may serve as a biomarker of the association between mood and nicotine among smokers. Implications for the results include (1) the use of DHEAS measurement across time and across quit attempts and (2) the potential for careful use of DHEA supplementation to facilitate abstinence during smoking cessation.

  16. Enteric YaiW Is a Surface-Exposed Outer Membrane Lipoprotein That Affects Sensitivity to an Antimicrobial Peptide

    PubMed Central

    Arnold, Markus F. F.; Caro-Hernandez, Paola; Tan, Karen; Runti, Giulia; Wehmeier, Silvia; Scocchi, Marco; Doerrler, William T.; Ferguson, Gail P.

    2014-01-01

    yaiW is a previously uncharacterized gene found in enteric bacteria that is of particular interest because it is located adjacent to the sbmA gene, whose bacA ortholog is required for Sinorhizobium meliloti symbiosis and Brucella abortus pathogenesis. We show that yaiW is cotranscribed with sbmA in Escherichia coli and Salmonella enterica serovar Typhi and Typhimurium strains. We present evidence that the YaiW is a palmitate-modified surface exposed outer membrane lipoprotein. Since BacA function affects the very-long-chain fatty acid (VLCFA) modification of S. meliloti and B. abortus lipid A, we tested whether SbmA function might affect either the fatty acid modification of the YaiW lipoprotein or the fatty acid modification of enteric lipid A but found that it did not. Interestingly, we did observe that E. coli SbmA suppresses deficiencies in the VLCFA modification of the lipopolysaccharide of an S. meliloti bacA mutant despite the absence of VLCFA in E. coli. Finally, we found that both YaiW and SbmA positively affect the uptake of proline-rich Bac7 peptides, suggesting a possible connection between their cellular functions. PMID:24214946

  17. Adverse reactions to cosmetics.

    PubMed

    Dogra, A; Minocha, Y C; Kaur, S

    2003-01-01

    Adverse reaction to cosmetics constitute a small but significant number of cases of contact dermatitis with varied appearances. These can present as contact allergic dermatitis, photodermatitis, contact irritant dermatitis, contact urticaria, hypopigmentation, hyperpigmentation or depigmentation, hair and nail breakage. Fifty patients were included for the study to assess the role of commonly used cosmetics in causing adverse reactions. It was found that hair dyes, lipsticks and surprisingly shaving creams caused more reaction as compared to other cosmetics. Overall incidence of contact allergic dermatitis seen was 3.3% with patients own cosmetics. Patch testing was also done with the basic ingredients and showed positive results in few cases where casual link could be established. It is recommended that labeling of the cosmetics should be done to help the dermatologists and the patients to identify the causative allergen in cosmetic preparation.

  18. Prothrombotic SERPINC1 gene polymorphism may affect heparin sensitivity among different ethnicities of Chinese patients receiving heart surgery.

    PubMed

    Wang, Jiang; Ma, Hai-Ping; Ti, Ai Lai Ti Ta Lai; Zhang, Yong-Qiang; Zheng, Hong

    2015-11-01

    The purpose of this study was to investigate a possible correlation between single-nucleotide polymorphisms (SNPs) of the antithrombin (gene, SERPINC1, and perioperative sensitivity to heparin in patients receiving heart surgery. The SERPINC1 genotype and allele frequency, coagulation parameters 24 hours before and after surgery, and clinical findings were compared among 3 ethnic groups, Han, Uighur, and Kazakh, patientswho received heart surgery. In Han patients, longer coagulation time as well as higher heparin and protamine dosage was observed. SERPINC1 gene sequencing identified 2 mutations in exon 5, g.981A>G (rs5877) and g.1011A>G (rs5878). The minor allele frequency of allele (A>G) for rs5877 and rs5878 was higher in the Han patients and was significantly different among the ethnic groups (P = .004 and P = .006, respectively). The increased SERPINC1 SNP frequency among Han patients receiving heart surgery might contribute to the differences in their perioperative sensitivity to heparin.

  19. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    PubMed Central

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  20. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate.

  1. High-anxiety rats are less sensitive to the rewarding affects of amphetamine on 50kHz USV.

    PubMed

    Lehner, Małgorzata H; Taracha, Ewa; Kaniuga, Ewelina; Wisłowska-Stanek, Aleksandra; Wróbel, Jacek; Sobolewska, Alicja; Turzyńska, Danuta; Skórzewska, Anna; Płaźnik, Adam

    2014-12-15

    This study assessed behaviour, as measured by 50kHz calls related to positive affect, in rats with different fear conditioned response strengths: low-anxiety rats (LR) and high-anxiety rats (HR), after amphetamine injection in a two-injection protocol (TIPS). The results showed that the first dose of amphetamine evoked similar behavioural effects in frequency-modulated (FM) 50kHz calls in the LR and HR groups. The second injection of amphetamine resulted in stronger FM 50kHz calls in LR compared with HR rats. The biochemical data ('ex vivo' analysis) showed that the LR rats had increased basal levels of dopamine in the amygdala, and increased homovanilic acid (HVA), dopamine's main metabolite, in the amygdala and prefrontal cortex compared with HR rats. The 'in vivo' analysis (microdialysis study) showed that the LR rats had increased HVA concentrations in the basolateral amygdala in response to an aversively conditioned context. Research has suggested that differences in dopaminergic system activity in the amygdala and prefrontal cortex may be one of the biological factors that underlie individual differences in response to fear stimuli, which may also affect the rewarding effects of amphetamine.

  2. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  3. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  4. The CYP3A4 inhibitor intraconazole does not affect the pharmacokinetics of a new calcium-sensitizing drug levosimendan.

    PubMed

    Antila, S; Honkanen, T; Lehtonen, L; Neuvonen, P J

    1998-08-01

    Itraconazole is a potent inhibitor of CYP3A4 isoenzyme and it can cause clinically significant interactions with some other drugs. Levosimendan is a new calcium-sensitizing drug intended for congestive heart failure. We aimed to study possible interactions of itraconazole with levosimendan in healthy volunteers. Twelve healthy male volunteers were included into a randomized, double-blind, two-phase crossover study. A wash-out period of 4 weeks was held between the phases. The subjects were given orally itraconazole 200 mg or placebo daily for 5 days. On the fifth day, they received a single oral dose of 2 mg of levosimendan. Levosimendan plasma concentrations were determined up to 12 hours and ECG, heart rate, and blood pressure followed-up to 8 hours after intake of levosimendan. Itraconazole had no significant effects on the pharmacokinetic parameters of levosimendan. Neither were there any differences in heart rate, PQ-, QTc- or QRS intervals between the placebo and itraconazole phases. The systolic blood pressure was decreased slightly more (p < 0.05) during the itraconazole phase than during the placebo phase. In conclusion, because the potent CYP3A4 inhibitor itraconazole had no significant pharmacokinetic interaction with levosimendan, interactions with CYP3A4 inhibitor, and oral levosimendan are unlikely.

  5. Autocrine interferon-γ may affect malignant behavior and sensitivity to tamoxifen of MCF-7 via estrogen receptor β subtype.

    PubMed

    Niu, Xiu Long; Wang, Yue; Yao, Zhi; Duan, Hongjie; Li, Zhijun; Liu, Wenxing; Zhang, Hongjian; Deng, Wei Min

    2015-12-01

    Mitogenic actions of estrogens are mediated by two distinct estrogen receptors (ERs), which are critical in the progression and therapeutic response of breast cancer. ER expression is a dynamic phenomenon that is regulated by numerous factors, including cytokines, in the tumor microenvironment. Recently, studies have shown that autocrine production of IL-4 promotes cancer cell growth and there is negative correlation between tumor IL-4 and hormone receptor levels, suggesting that there is crosstalk between cytokine receptors and ER. Thus, we evaluated for interaction between the two ERs and the cytokines IL-4 and IFN-γ, and if this interaction modulates malignant behavior. We identified that ERβ exerts protective activity in the progression of breast cancer cell line MCF-7, which co-expresses ERα and ERβ. IFN-γ and IL-4 have the opposite effects on malignant biological behavior. Furthermore, we found positive correlation between IFN-γ and ERβ expression in MCF-7. We also determined that autocrine IFN-γ in MCF-7 increases mRNA expression of ERβ resulting in enhanced sensitivity to tamoxifen (TAM). These results indicate that ERβ and autocrine IFN-γ represent two putative targets for breast cancer therapy.

  6. Vaccine adverse events.

    PubMed

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  7. [Adverse events prevention ability].

    PubMed

    Aparo, Ugo Luigi; Aparo, Andrea

    2007-03-01

    The issue of how to address medical errors is the key to improve the health care system performances. Operational evidence collected in the last five years shows that the solution is only partially linked to future technological developments. Cultural and organisational changes are mandatory to help to manage and drastically reduce the adverse events in health care organisations. Classical management, merely based on coordination and control, is inadequate. Proactive, self-organising network based structures must be put in place and managed using adaptive, fast evolving management tools. PMID:17484160

  8. [Adverse events prevention ability].

    PubMed

    Aparo, Ugo Luigi; Aparo, Andrea

    2007-03-01

    The issue of how to address medical errors is the key to improve the health care system performances. Operational evidence collected in the last five years shows that the solution is only partially linked to future technological developments. Cultural and organisational changes are mandatory to help to manage and drastically reduce the adverse events in health care organisations. Classical management, merely based on coordination and control, is inadequate. Proactive, self-organising network based structures must be put in place and managed using adaptive, fast evolving management tools.

  9. MicroRNA-144 affects radiotherapy sensitivity by promoting proliferation, migration and invasion of breast cancer cells.

    PubMed

    Yu, Lei; Yang, Yanming; Hou, Jiguang; Zhai, Chengwei; Song, Yunhao; Zhang, Zhiliang; Qiu, Ling; Jia, Xiaojing

    2015-10-01

    Radiotherapy resistance remains a major obstacle for patients with breast cancer. miRNAs are important regulators in many biological processes including proliferation, apoptosis, invasion and metastasis and response to treatment in different types of tumors. Here, we describe the role of miRNA-144 in the regulation of radiotherapy sensitivity, migration and invasion of breast cancer cells. The cell survival rate of breast cancer cells was measured by WST-1 assay after irradiation. The caspase-3/-7 activity and apoptotic proteins were analyzed by Caspase-Glo3/7 assay and western blot analysis, respectively. The migration and invasion of breast cancer cells were evaluated by BD Transwell migration and Matrigel invasion assays. The EMT markers were detected by western blot analysis. We found that overexpression of miR-144 increased the proliferation rate of MDA-MB-231 cells without radiation. Both MDA-MB‑231 and SKBR3 cells exhibited significantly increased radiation resistance after overexpression of miR-144. Meanwhile, the migration and invasion of both MDA-MB-231 and SKBR3 cells were changed by altered miR-144 expression. In addition, the overexpression of miR-144 inhibited E-cadherin expression and promoted Snail expression. miR-144 activated AKT by downregulation of PTEN in breast cancer cells. Our results strongly suggest that miR-144 acts as an important regulator of tumorigenesis and tumor progression of breast cancer. These results indicate that miR-144 might serve as a potential molecular target for breast cancer treatment.

  10. Series Length Used during Trend Analysis Affects Sensitivity to Changes in Progression Rate in the Ocular Hypertension Treatment Study

    PubMed Central

    Gardiner, Stuart K.; Demirel, Shaban; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M.; Cioffi, George A.; Ritch, Robert; Gordon, Mae O.; Kass, Michael A.

    2013-01-01

    Purpose. Trend analysis techniques to detect glaucomatous progression typically assume a constant rate of change. This study uses data from the Ocular Hypertension Treatment Study to assess whether this assumption decreases sensitivity to changes in progression rate, by including earlier periods of stability. Methods. Series of visual fields (mean 24 per eye) completed at 6-month intervals from participants randomized initially to observation were split into subseries before and after the initiation of treatment (the “split-point”). The mean deviation rate of change (MDR) was derived using these entire subseries, and using only the window length (W) tests nearest the split-point, for different window lengths of W tests. A generalized estimating equation model was used to detect changes in MDR occurring at the split-point. Results. Using shortened subseries with W = 7 tests, the MDR slowed by 0.142 dB/y upon initiation of treatment (P < 0.001), and the proportion of eyes showing “rapid deterioration” (MDR <–0.5 dB/y with P < 5%) decreased from 11.8% to 6.5% (P < 0.001). Using the entire sequence, no significant change in MDR was detected (P = 0.796), and there was no change in the proportion of eyes progressing (P = 0.084). Window lengths 6 ≤ W ≤ 9 produced similar benefits. Conclusions. Event analysis revealed a beneficial treatment effect in this dataset. This effect was not detected by linear trend analysis applied to entire series, but was detected when using shorter subseries of length between six and nine fields. Using linear trend analysis on the entire field sequence may not be optimal for detecting and monitoring progression. Nonlinear analyses may be needed for long series of fields. (ClinicalTrials.gov number, NCT00000125.) PMID:23349433

  11. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    PubMed

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects. PMID:25426064

  12. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    PubMed

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects.

  13. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    PubMed Central

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects. PMID:25426064

  14. Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

    PubMed Central

    Savelieva, Katerina V.; Rajan, Indrani; Yang, Qi; Cullinan, Emily; Lanthorn, Thomas H.

    2008-01-01

    The neurotransmitter serotonin (5-HT) plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2). We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO) and Tph1/Tph2 double knockout (DKO) mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders. PMID:18923670

  15. Modifying metabolically sensitive histone marks by inhibiting glutamine metabolism affects gene expression and alters cancer cell phenotype.

    PubMed

    Simpson, Natalie E; Tryndyak, Volodymyr P; Pogribna, Marta; Beland, Frederick A; Pogribny, Igor P

    2012-12-01

    The interplay of metabolism and epigenetic regulatory mechanisms has become a focal point for a better understanding of cancer development and progression. In this study, we have acquired data supporting previous observations that demonstrate glutamine metabolism affects histone modifications in human breast cancer cell lines. Treatment of non-invasive epithelial (T-47D and MDA-MB-361) and invasive mesenchymal (MDA-MB-231 and Hs-578T) breast cancer cell lines with the glutaminase inhibitor, Compound 968, resulted in cytotoxicity in all cell lines, with the greatest effect being observed in MDA-MB-231 breast cancer cells. Compound 968-treatment induced significant downregulation of 20 critical cancer-related genes, the majority of which are anti-apoptotic and/or promote metastasis, including AKT, BCL2, BCL2L1, CCND1, CDKN3, ERBB2, ETS1, E2F1, JUN, KITLG, MYB, and MYC. Histone H3K4me3, a mark of transcriptional activation, was reduced at the promoters of all but one of these critical cancer genes. The decrease in histone H3K4me3 at global and gene-specific levels correlated with reduced expression of SETD1 and ASH2L, genes encoding the histone H3K4 methyltransferase complex. Further, the expression of other epigenetic regulatory genes, known to be downregulated during apoptosis (e.g., DNMT1, DNMT3B, SETD1 and SIRT1), was also downregulated by Compound 968. These changes in gene expression and histone modifications were accompanied by the activation of apoptosis, and decreased invasiveness and resistance of MDA-MB-231 cells to chemotherapeutic drug doxorubicin. The results of this study provide evidence to a link between cytotoxicity caused by inhibiting glutamine metabolism with alterations of the epigenome of breast cancer cells and suggest that modification of intracellular metabolism may enhance the efficiency of epigenetic therapy. PMID:23117580

  16. Warmer winters modulate life history and energy storage but do not affect sensitivity to a widespread pesticide in an aquatic insect.

    PubMed

    Arambourou, Hélène; Stoks, Robby

    2015-10-01

    Despite the increased attention for the effects of pesticides under global warming no studies tested how winter warming affects subsequent sensitivity to pesticides. Winter warming is expected to cause delayed negative effects when it increases metabolic rates and thereby depletes energy reserves. Using a common-garden experiment, we investigated the combined effect of a 4 °C increase in winter temperature and subsequent exposure to chlorpyrifos in the aquatic larvae of replicated low- and high-latitude European populations of the damselfly Ischnura elegans. The warmer winter (8 °C) resulted in a higher winter survival and higher growth rates compared to the cold winter (4 °C) commonly experienced by European high-latitude populations. Low-latitude populations were better at coping with the warmer winter, indicating thermal adaptation to the local winter temperatures. Subsequent chlorpyrifos exposure at 20 °C induced strong negative effects on survival, growth rate, lipid content and acetylcholinesterase activity while phenoloxidase activity increased. These pesticide effects were not affected by winter warming. Our results suggest that for species where winter warming has positive effects on life history, no delayed effects on the sensitivity to subsequent pesticide exposure should be expected. PMID:26261878

  17. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  18. The direct and interactive effects of physical abuse severity and negative affectivity on length of psychiatric hospitalization: evidence of differential reactivity to adverse environments in psychiatrically high-risk youth.

    PubMed

    Comas, Michelle; Valentino, Kristin; Bridgett, David J; Hayden, Lisa C

    2014-01-01

    The current study examined the interactive influence of multiple factors (i.e., physical abuse severity and negative affectivity) in predicting youth's inpatient psychiatric length of stay (LOS), extending previous research focused on identification of only single LOS predictors. Elevated physical abuse severity was hypothesized to predict longer youth LOS, and negative affectivity was anticipated to exacerbate this relationship. This study included 42 youth. Clinicians rated youth temperament, whereas physical abuse severity and LOS were coded from youth medical records. Controlling for other previously determined predictors of LOS (i.e., age, gender, and GAF), moderation analyses confirmed hypotheses, revealing a temperament by environment interaction. Specifically, physical abuse severity was positively associated with LOS only in the context of high negative affectivity. Findings highlighted the importance of disentangling the interactive effects of multiple factors in predicting LOS. Moreover, critical clinical implications involving prioritized trauma assessment and treatment for inpatient youth are discussed.

  19. Glycosylation of Residue 141 of Subtype H7 Influenza A Hemagglutinin (HA) Affects HA-Pseudovirus Infectivity and Sensitivity to Site A Neutralizing Antibodies

    PubMed Central

    Alvarado-Facundo, Esmeralda; Vassell, Russell; Schmeisser, Falko; Weir, Jerry P.; Weiss, Carol D.; Wang, Wei

    2016-01-01

    Human infections with H7 subtype influenza virus have been reported, including an H7N7 outbreak in Netherlands in 2003 and H7N9 infections in China in 2013. Previously, we reported murine monoclonal antibodies (mAbs) that recognize the antigenic site A of H7 hemagglutinin (HA). To better understand protective immunity of H7 vaccines and vaccine candidate selection, we used these mAbs to assess the antigenic relatedness among two H7 HA isolated from past human infections and determine residues that affect susceptibility to neutralization. We found that these mAbs neutralize pseudoviruses bearing HA of A/Shanghai/02/2013(H7N9), but not A/Netherlands/219/2003(H7N7). Glycosylation of the asparagine residue at position 141 (N141) (N133, H3 HA numbering) in the HA of A/Netherlands/219/2003 HA is responsible for this resistance, and it affects the infectivity of HA-pseudoviruses. The presence of threonine at position 143 (T135, H3 HA numbering) in the HA of A/Netherlands/219/2003, rather than an alanine found in the HA of A/Shanghai/02/2013(H7N9), accounts for these differences. These results demonstrate a key role for glycosylation of residue N141 in affecting H7 influenza HA-mediated entry and sensitivity to neutralizing antibodies, which have implications for candidate vaccine design. PMID:26862918

  20. ADVERSE DRUG REACTIONS IN THE ORAL CAVITY.

    PubMed

    Boras, Vanja Vučićević; Andabak-Rogulj, Ana; Brailo, Vlaho; Šimunković, Sonja Kraljević; Gabrić, Dragana; Vrdoljak, Danko Velimir

    2015-06-01

    Every medication may lead to adverse effects, even when used in standard doses and mode of application. In the oral cavity, adverse effects may affect every part of oral mucosa and are the result of medications taken either locally or systemically. Oral adverse reactions to drugs are not typical and therefore sometimes not easy to recognize. On diagnosing adverse side effects in the oral cavity, experienced clinician will usually diagnose the condition on the basis of detailed medical history and clinical finding. However, the only objective evidence for the offending drug is 're-challenge', i.e. exposure to the drug after its discontinuation. It carries a huge risk of anaphylactic reaction; therefore it has to be performed in a controlled hospital setting. Therapy is based on immediate exclusion of the offending drug and, if lesions are present in the oral cavity, topical or systemic corticosteroid therapy is prescribed. This article gives a review of patients with oral adverse drug reactions referred to the Department of Oral Medicine in Zagreb.

  1. Adverse childhood experiences and health anxiety in adulthood.

    PubMed

    Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

    2014-03-01

    Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety. PMID:24011493

  2. The B-3 ethylene response factor MtERF1-1 mediates resistance to a subset of root pathogens in Medicago truncatula without adversely affecting symbiosis with rhizobia.

    PubMed

    Anderson, Jonathan P; Lichtenzveig, Judith; Gleason, Cynthia; Oliver, Richard P; Singh, Karam B

    2010-10-01

    The fungal necrotrophic pathogen Rhizoctonia solani is a significant constraint to a range of crops as diverse as cereals, canola, and legumes. Despite wide-ranging germplasm screens in many of these crops, no strong genetic resistance has been identified, suggesting that alternative strategies to improve resistance are required. In this study, we characterize moderate resistance to R. solani anastomosis group 8 identified in Medicago truncatula. The activity of the ethylene- and jasmonate-responsive GCC box promoter element was associated with moderate resistance, as was the induction of the B-3 subgroup of ethylene response transcription factors (ERFs). Genes of the B-1 subgroup showed no significant response to R. solani infection. Overexpression of a B-3 ERF, MtERF1-1, in Medicago roots increased resistance to R. solani as well as an oomycete root pathogen, Phytophthora medicaginis, but not root knot nematode. These results indicate that targeting specific regulators of ethylene defense may enhance resistance to an important subset of root pathogens. We also demonstrate that overexpression of MtERF1-1 enhances disease resistance without apparent impact on nodulation in the A17 background, while overexpression in sickle reduced the hypernodulation phenotype. This suggests that under normal regulation of nodulation, enhanced resistance to root diseases can be uncoupled from symbiotic plant-microbe interactions in the same tissue and that ethylene/ERF regulation of nodule number is distinct from the defenses regulated by B-3 ERFs. Furthermore, unlike the stunted phenotype previously described for Arabidopsis (Arabidopsis thaliana) ubiquitously overexpressing B-3 ERFs, overexpression of MtERF1-1 in M. truncatula roots did not show adverse effects on plant development.

  3. COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence.

    PubMed

    Schellekens, Arnt F A; Franke, Barbara; Ellenbroek, Bart; Cools, Alexander; de Jong, Cor A J; Buitelaar, Jan K; Verkes, Robbert-Jan

    2013-03-01

    Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene-environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene-environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.

  4. TRICHOME BIREFRINGENCE-LIKE27 affects aluminum sensitivity by modulating the O-acetylation of xyloglucan and aluminum-binding capacity in Arabidopsis.

    PubMed

    Zhu, Xiao Fang; Sun, Ying; Zhang, Bao Cai; Mansoori, Nasim; Wan, Jiang Xue; Liu, Yu; Wang, Zhi Wei; Shi, Yuan Zhi; Zhou, Yi Hua; Zheng, Shao Jian

    2014-09-01

    Xyloglucan (XyG) has been reported to contribute to the aluminum (Al)-binding capacity of the cell wall in Arabidopsis (Arabidopsis thaliana). However, the influence of O-acetylation of XyG, accomplished by the putative O-acetyltransferase TRICHOME BIREFRINGENCE-LIKE27 (TBL27 [AXY4]), on its Al-binding capacity is not known. In this study, we found that the two corresponding TBL27 mutants, axy4-1 and axy4-3, were more Al sensitive than wild-type Columbia-0 plants. TBL27 was expressed in roots as well as in leaves, stems, flowers, and siliques. Upon Al treatment, even within 30 min, TBL27 transcript accumulation was strongly down-regulated. The mutants axy4-1 and axy4-3 accumulated significantly more Al in the root and wall, which could not be correlated with pectin content or pectin methylesterase activity, as no difference in the mutants was observed compared with the wild type when exposed to Al stress. The increased Al accumulation in the wall of the mutants was found to be in the hemicellulose fraction. While the total sugar content of the hemicellulose fraction did not change, the O-acetylation level of XyG was reduced by Al treatment. Taken together, we conclude that modulation of the O-acetylation level of XyG influences the Al sensitivity in Arabidopsis by affecting the Al-binding capacity in the hemicellulose. PMID:25006026

  5. A temperature-sensitive mutation affecting cilia regeneration, nuclear development, and the cell cycle of Tetrahymena thermophila is rescued by cytoplasmic exchange

    SciTech Connect

    Pennock, D.G.; Thatcher, T.; Gorovsky, M.A. )

    1988-07-01

    A temperature-sensitive mutation was isolated that blocks cilia regeneration and arrests growth in Tetrahymena thermophila. Protein and RNA synthesis and ATP production appeared to be largely unaffected at the restrictive temperature, suggesting that the mutation is specific for cilia regeneration and growth. At the restrictive temperature, mutant cells arrested at a specific point in the cell cycle, after macronuclear S phase and shortly before micronuclear mitosis. Arrested cels did not undergo nuclear divisions, DNA replication, or cytokinesis, so the mutation appears to cause true cell cycle arrest. Surprisingly, the mutation des not appear to affect micronuclear mitosis directly but rather some event(s) prior to micronuclear mitosis that must be completed before cells can complete the cell cycle. The cell cycle arrest was transiently complemented by wild-type cytoplasm exchanged during conjugation with a wild-type cell. Each starved, wild-type cell apparently contained enough rescuing factor to support an average of six cell divisions. Thus, this mutation affects assembly and/or function of at least one but not al of the microtubule-based structures in T. thermophila.

  6. Sensitivity of the Autonomic Nervous System to Visual and Auditory Affect Across Social and Non-Social Domains in Williams Syndrome

    PubMed Central

    Järvinen, Anna; Dering, Benjamin; Neumann, Dirk; Ng, Rowena; Crivelli, Davide; Grichanik, Mark; Korenberg, Julie R.; Bellugi, Ursula

    2012-01-01

    Although individuals with Williams syndrome (WS) typically demonstrate an increased appetitive social drive, their social profile is characterized by dissociations, including socially fearless behavior coupled with anxiousness, and distinct patterns of “peaks and valleys” of ability. The aim of this study was to compare the processing of social and non-social visually and aurally presented affective stimuli, at the levels of behavior and autonomic nervous system (ANS) responsivity, in individuals with WS contrasted with a typically developing (TD) group, with the view of elucidating the highly sociable and emotionally sensitive predisposition noted in WS. Behavioral findings supported previous studies of enhanced competence in processing social over non-social stimuli by individuals with WS; however, the patterns of ANS functioning underlying the behavioral performance revealed a surprising profile previously undocumented in WS. Specifically, increased heart rate (HR) reactivity, and a failure for electrodermal activity to habituate were found in individuals with WS contrasted with the TD group, predominantly in response to visual social affective stimuli. Within the auditory domain, greater arousal linked to variation in heart beat period was observed in relation to music stimuli in individuals with WS. Taken together, the findings suggest that the pattern of ANS response in WS is more complex than previously noted, with increased arousal to face and music stimuli potentially underpinning the heightened behavioral emotionality to such stimuli. The lack of habituation may underlie the increased affiliation and attraction to faces characterizing individuals with WS. Future research directions are suggested. PMID:23049519

  7. Exposure to early adversity: Points of cross-species translation that can lead to improved understanding of depression.

    PubMed

    Andersen, Susan L

    2015-05-01

    The relationship between developmental exposure to adversity and affective disorders is reviewed. Adversity discussed herein includes physical and sexual abuse, neglect, or loss of a caregiver in humans. While these stressors can occur at any point during development, the unique temporal relationship to specific depressive symptoms was the focus of discussion. Further influences of stress exposure during sensitive periods can vary by gender and duration of abuse as well. Data from animal studies are presented to provide greater translational and causal understanding of how sensitive periods, different types of psychosocial stressors, and sex interact to produce depressive-like behaviors. Findings from maternal separation, isolation rearing, chronic variable stress, and peer-peer rearing paradigms clarify interpretation about how various depressive behaviors are influenced by age of exposure. Depressive behaviors are broken down into the following categories: mood and affect, anhedonia, energy, working memory, sleep-wake, appetite changes, suicide, and general malaise. Cross-species evidence from humans, nonhuman primates, rats, and mice within each of these categories is discussed. In conclusion, sensitive periods for affective-related behaviors (anxiety, mood, and controllability) occur earlier in life, while other aspects of depression are associated with adversity later during adolescence. PMID:25997766

  8. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.

  9. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence. PMID:23850228

  10. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment.

  11. Adverse reaction to lupine-fortified pasta.

    PubMed

    Hefle, S L; Lemanske, R F; Bush, R K

    1994-08-01

    A 5-year-old girl with peanut sensitivity experienced urticaria and angioedema after ingesting a spaghetti-like pasta fortified with sweet lupine seed flour. The pasta was extracted and used in immunologic studies in patients with peanut sensitivity to determine whether such individuals are at similar risk. Results of skin prick tests with the lupine pasta extract were positive in five of seven subjects; these patients also reported a history of adverse reactions to green peas. In direct RAST studies IgE binding from pooled sera from patients with peanut sensitivity to the lupine pasta extract was 7 times that of a nonallergic control serum, and individual serum samples demonstrated binding from 1 to 6 times that of the negative control. Direct RAST studies of lupine seed flour with serum samples from patients with peanut allergy demonstrated IgE binding 1 to 11 times that of the negative control. Immunoblotting studies of electrophoretically separated pasta extract and lupine seed flour proteins showed IgE-binding protein bands at approximately 21 kd and in the range of 35 to 55 kd molecular weight. We conclude that some peanut-sensitive patients may be at risk for adverse reactions to lupine.

  12. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  13. Adverse reactions to the sulphite additives

    PubMed Central

    Misso, Neil LA

    2012-01-01

    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. Most studies report a prevalence of sulphite sensitivity of 3 to 10% among asthmatic subjects who ingest these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. Although a number of potential mechanisms have been proposed, the precise mechanisms underlying sulphite sensitivity remain unclear. PMID:24834193

  14. The Use of Fish Oil with Warfarin Does Not Significantly Affect either the International Normalised Ratio or Incidence of Adverse Events in Patients with Atrial Fibrillation and Deep Vein Thrombosis: A Retrospective Study

    PubMed Central

    Pryce, Rebecca; Bernaitis, Nijole; Davey, Andrew K.; Badrick, Tony; Anoopkumar-Dukie, Shailendra

    2016-01-01

    Background: Warfarin is a leading anticoagulant in the management of atrial fibrillation (AF) and deep vein thrombosis (DVT). Drug interactions influence the safety of warfarin use and while extensive literature exists regarding the effect on warfarin control and bleeding incidence with many medicines, there is little evidence on the influence of complementary medicines. The aim of this study was to assess the influence of fish and krill oil supplementation on warfarin control and bleeding incidence in AF and DVT patients. Methods: A retrospective analysis was conducted utilising patient information from a large private pathology clinic. AF and DVT patients receiving long-term warfarin therapy (>30 days) at the clinic and taking fish and krill oil supplements were eligible for study inclusion. Results: Of the 2081 patients assessed, a total of 573 warfarin users met the inclusion criteria with 145 patients in the fish and krill oil group (supplement group) and 428 patients in the control group. Overall, it was found that fish and krill oils did not significantly alter warfarin time in therapeutic range (TTR) or bleeding incidence, even when compared by gender. Conclusion: Omega-3 supplementation with fish and krill oil does not significantly affect long-term warfarin control and bleeding and thromboembolic events when consumed concurrently in patients managed at an anticoagulation clinic. PMID:27657121

  15. Linezolid Induced Adverse Drug Reactions - An Update.

    PubMed

    Kishor, Kamal; Dhasmana, Neha; Kamble, Shashank Shivaji; Sahu, Roshan Kumar

    2015-01-01

    Treatment regimen recommended for resistant tuberculosis consists of various drugs and these drugs are prescribed for at least 12-15 months. Such a long duration therapy and high dose of antibiotics result in adverse drug reactions (ADRs). ADRs may lead to various complications in disease management like replacement of drugs, dose increment, therapy withdrawal, etc. Linezolid is one of those drugs, practiced as an anti-mycobacterial agent and it is an important member of drug regimen for MDR and XDR tuberculosis. Linezolid is a broad spectrum antibiotic known for its unique mechanism of inhibition of resistant pathogenic strains. However, it causes serious adverse effects like thrombocytopenia, optic neuropathy, peripheral neuropathy, lactic acidosis, etc. Literature suggests that Linezolid can cause severe ADRs which affect patient compliance and hinder in therapy to a larger extent. Recent studies confirm the possibility of ADRs to be predicted with genetic make-up of individuals. To effectively deliver the available treatment regimen and ensure patient compliance, it is important to manage ADRs more efficiently. The role of pharmacogenomics in reducing adverse drug effects has been recently explored. In the present review, we discussed about Linezolid induced adverse drug reactions, mechanisms and genetic associations. PMID:26424176

  16. Adverse Stress, Hippocampal Networks, and Alzheimer's Disease

    PubMed Central

    Rothman, Sarah M.; Mattson, Mark P.

    2009-01-01

    Recent clinical data have implicated chronic adverse stress as a potential risk factor in the development of Alzheimer's disease (AD) and data also suggest that normal, physiological stress responses may be impaired in AD. It is possible that pathology associated with AD causes aberrant responses to chronic stress, due to potential alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Recent work in rodent models of AD suggests that chronic adverse stress exacerbates the cognitive deficits and hippocampal pathology that are present in the AD brain. This review summarizes recent findings obtained in experimental AD models regarding the influence of chronic adverse stress on the underlying cellular and molecular disease processes including the potential role of glucocorticoids. Emerging findings suggest that both AD and chronic adverse stress affect hippocampal neural networks in a similar fashion. We describe alterations in hippocampal plasticity that occur in both chronic stress and AD including dendritic remodeling, neurogenesis and long-term potentiation. Finally, we outline potential roles for oxidative stress and neurotrophic factor signaling as key determinants of the impact of chronic stress on the plasticity of neural networks and AD pathogenesis. PMID:19943124

  17. 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze

    PubMed Central

    Karabeg, Margherita M.; Grauthoff, Sandra; Kollert, Sina Y.; Weidner, Magdalena; Heiming, Rebecca S.; Jansen, Friederike; Popp, Sandy; Kaiser, Sylvia; Lesch, Klaus-Peter; Sachser, Norbert

    2013-01-01

    The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised

  18. Tmc1 Point Mutation Affects Ca2+ Sensitivity and Block by Dihydrostreptomycin of the Mechanoelectrical Transducer Current of Mouse Outer Hair Cells

    PubMed Central

    Corns, Laura F.; Johnson, Stuart L.; Kros, Corné J.

    2016-01-01

    The transduction of sound into electrical signals depends on mechanically sensitive ion channels in the stereociliary bundle. The molecular composition of this mechanoelectrical transducer (MET) channel is not yet known. Transmembrane channel-like protein isoforms 1 (TMC1) and 2 (TMC2) have been proposed to form part of the MET channel, although their exact roles are still unclear. Using Beethoven (Tmc1Bth/Bth) mice, which have an M412K point mutation in TMC1 that adds a positive charge, we found that Ca2+ permeability and conductance of the MET channel of outer hair cells (OHCs) were reduced. Tmc1Bth/Bth OHCs were also less sensitive to block by the permeant MET channel blocker dihydrostreptomycin, whether applied extracellularly or intracellularly. These findings suggest that the amino acid that is mutated in Bth is situated at or near the negatively charged binding site for dihydrostreptomycin within the permeation pore of the channel. We also found that the Ca2+ dependence of the operating range of the MET channel was altered by the M412K mutation. Depolarization did not increase the resting open probability of the MET current of Tmc1Bth/Bth OHCs, whereas raising the intracellular concentration of the Ca2+ chelator BAPTA caused smaller increases in resting open probability in Bth mutant OHCs than in wild-type control cells. We propose that these observations can be explained by the reduced Ca2+ permeability of the mutated MET channel indirectly causing the Ca2+ sensor for adaptation, at or near the intracellular face of the MET channel, to become more sensitive to Ca2+ influx as a compensatory mechanism. SIGNIFICANCE STATEMENT In the auditory system, the hair cells convert sound-induced mechanical movement of the hair bundles atop these cells into electrical signals through the opening of mechanically gated ion channels at the tips of the bundles. Although the nature of these mechanoelectrical transducer (MET) channels is still unclear, recent studies implicate

  19. Xyloglucan Endotransglucosylase-Hydrolase17 Interacts with Xyloglucan Endotransglucosylase-Hydrolase31 to Confer Xyloglucan Endotransglucosylase Action and Affect Aluminum Sensitivity in Arabidopsis1[OPEN

    PubMed Central

    Zhu, Xiao Fang; Wan, Jiang Xue; Sun, Ying; Shi, Yuan Zhi; Braam, Janet; Li, Gui Xin; Zheng, Shao Jian

    2014-01-01

    Previously, we reported that although the Arabidopsis (Arabidopsis thaliana) Xyloglucan Endotransglucosylase-Hydrolase31 (XTH31) has predominately xyloglucan endohydrolase activity in vitro, loss of XTH31 results in remarkably reduced in vivo xyloglucan endotransglucosylase (XET) action and enhanced Al resistance. Here, we report that XTH17, predicted to have XET activity, binds XTH31 in yeast (Saccharomyces cerevisiae) two-hybrid and coimmunoprecipitations assays and that this interaction may be required for XTH17 XET activity in planta. XTH17 and XTH31 may be colocalized in plant cells because tagged XTH17 fusion proteins, like XTH31 fusion proteins, appear to target to the plasma membrane. XTH17 expression, like that of XTH31, was substantially reduced in the presence of aluminum (Al), even at concentrations as low as 10 µm for 24 h or 25 µm for just 30 min. Agrobacterium tumefaciens-mediated transfer DNA insertion mutant of XTH17, xth17, showed low XET action and had moderately shorter roots than the wild type but was more Al resistant than the wild type. Similar to xth31, xth17 had low hemicellulose content and retained less Al in the cell wall. These data suggest a model whereby XTH17 and XTH31 may exist as a dimer at the plasma membrane to confer in vivo XET action, which modulates cell wall Al-binding capacity and thereby affects Al sensitivity in Arabidopsis. PMID:24948835

  20. Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair

    PubMed Central

    Penterling, Corina; Drexler, Guido A.; Böhland, Claudia; Stamp, Ramona; Wilke, Christina; Braselmann, Herbert; Caldwell, Randolph B.; Reindl, Judith; Girst, Stefanie; Greubel, Christoph; Siebenwirth, Christian; Mansour, Wael Y.; Borgmann, Kerstin; Dollinger, Günther; Unger, Kristian; Friedl, Anna A.

    2016-01-01

    Histone demethylases have recently gained interest as potential targets in cancer treatment and several histone demethylases have been implicated in the DNA damage response. We investigated the effects of siRNA-mediated depletion of histone demethylase Jarid1A (KDM5A, RBP2), which demethylates transcription activating tri- and dimethylated lysine 4 at histone H3 (H3K4me3/me2), on growth characteristics and cellular response to radiation in several cancer cell lines. In unirradiated cells Jarid1A depletion lead to histone hyperacetylation while not affecting cell growth. In irradiated cells, depletion of Jarid1A significantly increased cellular radiosensitivity. Unexpectedly, the hyperacetylation phenotype did not lead to disturbed accumulation of DNA damage response and repair factors 53BP1, BRCA1, or Rad51 at damage sites, nor did it influence resolution of radiation-induced foci or rejoining of reporter constructs. We conclude that the radiation sensitivity observed following depletion of Jarid1A is not caused by a deficiency in repair of DNA double-strand breaks. PMID:27253695

  1. Adverse effects of general anaesthetics.

    PubMed

    Berthoud, M C; Reilly, C S

    1992-01-01

    This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis. PMID:1418699

  2. Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment

    PubMed Central

    El Hajj, Nady; Schneider, Eberhard; Lehnen, Harald; Haaf, Thomas

    2014-01-01

    The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as ‘developmental origins of health and disease (DOHAD)’ or ‘Barker’ hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene–environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10–20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease. PMID:25187623

  3. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    PubMed Central

    Moral, Angel; Moreno, Victoria; Girón, Francisco; El-Qutob, David; Moure, José D; Alcántara, Manuel; Padial, Antonia; Oehling, Alberto G; Millán, Carmen; de la Torre, Fernando

    2016-01-01

    Background Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. Patients and methods A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. Results The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). Conclusion In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. PMID:27418842

  4. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  5. Docosahexaenoic Acid Sensitizes Leukemia Lymphocytes to Barasertib and Everolimus by ROS-dependent Mechanism Without Affecting the Level of ROS and Viability of Normal Lymphocytes.

    PubMed

    Zhelev, Zhivko; Ivanova, Donika; Lazarova, Desislava; Aoki, Ichio; Bakalova, Rumiana; Saga, Tsuneo

    2016-04-01

    The aim of the present study was: (i) to investigate the possibility of sensitizing leukemia lymphocytes to anticancer drugs using docosahexaenoic acid (DHA); (ii) to find combinations with synergistic cytotoxic effect on leukemia lymphocytes, without or with only very low cytotoxicity towards normal lymphocytes; (iii) and to clarify the role of reactive oxygen species (ROS) in the induction of apoptosis and cytotoxicity by such combinations. The study covered 15 anticancer drugs, conventional and new-generation. Well-expressed synergistic cytotoxic effects were observed after treatment of leukemia lymphocytes (Jurkat) with DHA in combination with: barasertib, lonafarnib, everolimus, and palbociclib. We selected two synergistic combinations, DHA with everolimus or barasertib, and investigated their effects on viability of normal lymphocytes, as well as on the production of ROS and induction of apoptosis in both cell lines (leukemia and normal). At the selected concentrations, DHA, everolimus and barasertib (applied separately) were cytotoxic towards leukemia lymphocytes, but not normal lymphocytes. In leukemia cells, the cytotoxicity of combinations was accompanied by strong induction of apoptosis and production of ROS. In normal lymphocytes, drugs alone and in combination with DHA did not affect the level of ROS and did not induce apoptosis. To our knowledge, the present study is the first to report synergistic ROS-dependent cytotoxicity between DHA and new-generation anticancer drugs, such as everolimus and barasertib, that is cancer cell-specific (particularly for acute lymphoblastic leukemia cells Jurkat). These combinations are harmless to normal lymphocytes and do not induce abnormal production of ROS in these cells. The data suggest that DHA could be used as a supplementary component in anticancer chemotherapy, allowing therapeutic doses of everolimus and barasertib to be reduced, minimizing their side-effects. PMID:27069145

  6. Diets High in Protein or Saturated Fat Do Not Affect Insulin Sensitivity or Plasma Concentrations of Lipids and Lipoproteins in Overweight and Obese Adults123

    PubMed Central

    Chiu, Sally; Williams, Paul T.; Dawson, Taylor; Bergman, Richard N.; Stefanovski, Darko; Watkins, Steven M.; Krauss, Ronald M.

    2014-01-01

    Background: Previous human studies reported inconsistent effects of dietary protein and branched-chain amino acids (BCAAs) on insulin action and glucose metabolism. Similarly, it is unclear whether saturated fat (SF) intake influences these metabolic variables. Objective: The objective of this study was to test the effects of high [30% of energy (%E)] vs. moderate (20%E) intakes of protein (primarily whey) on insulin action and lipid and lipoprotein concentrations in the context of both high (15%E) and low (7%E) SF diets. Methods: The study was conducted as a randomized controlled trial in 158 overweight and obese men and women. After a 4-wk baseline diet [55%E carbohydrate, 15%E protein, 30%E fat (7%E SF)], participants were randomly assigned to 4 wk of either the baseline diet or 1 of 4 test diets containing 35%E carbohydrate and either 20%E or 30%E protein and either 7%E or 15%E SF. Frequently sampled i.v. glucose tolerance tests were administered after each dietary period. Results: Other than significantly higher fasting glucose concentrations for high vs. moderate protein intakes with a low-fat diet (difference ± SE: 0.47 ± 0.14 mmol/L; P = 0.001), there were no significant effects of dietary protein or SF on glucose metabolism, plasma insulin, or concentrations of lipids and lipoproteins. Changes in plasma BCAAs across all diets were negatively correlated with changes in the metabolic clearance rate of insulin (ρ = −0.18, P = 0.03) and positively correlated with changes in the acute insulin response to glucose (ρ = 0.15, P = 0.05). Conclusions: These findings suggest that short-term intake of BCAAs can influence insulin dynamics. However, in this group of overweight and obese individuals, neither high protein nor SF intake affected insulin sensitivity or plasma concentrations of lipids and lipoproteins. This trial was registered at clinicaltrials.gov as NCT00508937. PMID:25332473

  7. ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents.

    PubMed

    Mancarella, Caterina; Casanova-Salas, Irene; Calatrava, Ana; Ventura, Selena; Garofalo, Cecilia; Rubio-Briones, José; Magistroni, Vera; Manara, Maria Cristina; López-Guerrero, José Antonio; Scotlandi, Katia

    2015-06-30

    Identifying patients who may benefit from targeted therapy is an urgent clinical issue in prostate cancer (PCa). We investigated the molecular relationship between TMPRSS2-ERG (T2E) fusion gene and insulin-like growth factor receptor (IGF-1R) to optimize the use of IGF-1R inhibitors.IGF-1R was analyzed in cell lines and in radical prostatectomy specimens in relation to T2E status. ERG binding to IGF-1R promoter was evaluated by chromatin immunoprecipitation (ChIP). Sensitivity to anti-IGF-1R agents was evaluated alone or in combination with anti-androgen abiraterone acetate in vitro at basal levels or upon ERG modulation.IGF-1R analysis performed in PCa cells or clinical samples showed that T2E expression correlated with higher IGF-1R expression at mRNA and protein levels. Genetic modulation of ERG directly affected IGF-1R protein levels in vitro. ChIP analysis showed that ERG binds IGF-1R promoter and that promoter occupancy is higher in T2E-positive cells. IGF-1R inhibition was more effective in cell lines expressing the fusion gene and combination of IGF-1R inhibitors with abiraterone acetate produced synergistic effects in T2E-expressing cells.Here, we provide the rationale for use of T2E fusion gene to select PCa patients for anti-IGF-1R treatments. The combination of anti-IGF-1R-HAbs with an anti-androgen therapy is strongly advocated for patients expressing T2E.

  8. ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents

    PubMed Central

    Mancarella, Caterina; Casanova-Salas, Irene; Calatrava, Ana; Ventura, Selena; Garofalo, Cecilia; Rubio-Briones, José; Magistroni, Vera; Manara, Maria Cristina; López-Guerrero, José Antonio; Scotlandi, Katia

    2015-01-01

    Identifying patients who may benefit from targeted therapy is an urgent clinical issue in prostate cancer (PCa). We investigated the molecular relationship between TMPRSS2-ERG (T2E) fusion gene and insulin-like growth factor receptor (IGF-1R) to optimize the use of IGF-1R inhibitors. IGF-1R was analyzed in cell lines and in radical prostatectomy specimens in relation to T2E status. ERG binding to IGF-1R promoter was evaluated by chromatin immunoprecipitation (ChIP). Sensitivity to anti-IGF-1R agents was evaluated alone or in combination with anti-androgen abiraterone acetate in vitro at basal levels or upon ERG modulation. IGF-1R analysis performed in PCa cells or clinical samples showed that T2E expression correlated with higher IGF-1R expression at mRNA and protein levels. Genetic modulation of ERG directly affected IGF-1R protein levels in vitro. ChIP analysis showed that ERG binds IGF-1R promoter and that promoter occupancy is higher in T2E-positive cells. IGF-1R inhibition was more effective in cell lines expressing the fusion gene and combination of IGF-1R inhibitors with abiraterone acetate produced synergistic effects in T2E-expressing cells. Here, we provide the rationale for use of T2E fusion gene to select PCa patients for anti-IGF-1R treatments. The combination of anti-IGF-1R-HAbs with an anti-androgen therapy is strongly advocated for patients expressing T2E. PMID:25906745

  9. Race, racism, and racial disparities in adverse birth outcomes.

    PubMed

    Dominguez, Tyan Parker

    2008-06-01

    While the biologic authenticity of race remains a contentious issue, the social significance of race is indisputable. The chronic stress of racism and the social inequality it engenders may be underlying social determinants of persistent racial disparities in health, including infant mortality, preterm delivery, and low birth weight. This article describes the problem of racial disparities in adverse birth outcomes; outlines the multidimensional nature of racism and the pathways by which it may adversely affect health; and discusses the implications for clinical practice.

  10. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors.

  11. Mu opioid receptor polymorphism, early social adversity, and social traits.

    PubMed

    Carver, Charles S; Johnson, Sheri L; Kim, Youngmee

    2016-10-01

    A polymorphism in the mu opioid receptor gene OPRM1 (rs1799971) has been investigated for its role in sensitivity to social contexts. Evidence suggests that the G allele of this polymorphism is associated with higher levels of sensitivity. This study tested for main effects of the polymorphism and its interaction with a self-report measure of childhood adversity as an index of negative environment. Outcomes were several personality measures relevant to social connection. Significant interactions were obtained, such that the negative impact of childhood adversity on personality was greater among G carriers than among A homozygotes on measures of agreeableness, interdependence, anger proneness, hostility, authentic pride, life engagement, and an index of (mostly negative) feelings coloring one's world view. Findings support the role of OPRM1 in sensitivity to negative environments. Limitations are noted, including the lack of a measure of advantageous social environment to assess sensitivity to positive social contexts.

  12. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  13. Adverse weather impacts on arable cropping systems

    NASA Astrophysics Data System (ADS)

    Gobin, Anne

    2016-04-01

    Damages due to extreme or adverse weather strongly depend on crop type, crop stage, soil conditions and management. The impact is largest during the sensitive periods of the farming calendar, and requires a modelling approach to capture the interactions between the crop, its environment and the occurrence of the meteorological event. The hypothesis is that extreme and adverse weather events can be quantified and subsequently incorporated in current crop models. Since crop development is driven by thermal time and photoperiod, a regional crop model was used to examine the likely frequency, magnitude and impacts of frost, drought, heat stress and waterlogging in relation to the cropping season and crop sensitive stages. Risk profiles and associated return levels were obtained by fitting generalized extreme value distributions to block maxima for air humidity, water balance and temperature variables. The risk profiles were subsequently confronted with yields and yield losses for the major arable crops in Belgium, notably winter wheat, winter barley, winter oilseed rape, sugar beet, potato and maize at the field (farm records) to regional scale (statistics). The average daily vapour pressure deficit (VPD) and reference evapotranspiration (ET0) during the growing season is significantly lower (p < 0.001) and has a higher variability before 1988 than after 1988. Distribution patterns of VPD and ET0 have relevant impacts on crop yields. The response to rising temperatures depends on the crop's capability to condition its microenvironment. Crops short of water close their stomata, lose their evaporative cooling potential and ultimately become susceptible to heat stress. Effects of heat stress therefore have to be combined with moisture availability such as the precipitation deficit or the soil water balance. Risks of combined heat and moisture deficit stress appear during the summer. These risks are subsequently related to crop damage. The methodology of defining

  14. Psychiatric adverse effects of pediatric corticosteroid use.

    PubMed

    Drozdowicz, Linda B; Bostwick, J Michael

    2014-06-01

    Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions

  15. Young Children's Affective Responses to Acceptance and Rejection from Peers: A Computer-Based Task Sensitive to Variation in Temperamental Shyness and Gender

    ERIC Educational Resources Information Center

    Howarth, Grace Z.; Guyer, Amanda E.; Perez-Edgar, Koraly

    2013-01-01

    This study presents a novel task examining young children's affective responses to evaluative feedback--specifically, social acceptance and rejection--from peers. We aimed to determine (1) whether young children report their affective responses to hypothetical peer evaluation predictably and consistently, and (2) whether young children's responses…

  16. NaCl does not affect hypothalamic noradrenergic input in deoxycorticosterone acetate/NaCl and Dahl salt-sensitive rats.

    PubMed

    Chen, Y F; Meng, Q C; Wyss, J M; Jin, H K; Rogers, C F; Oparil, S

    1990-07-01

    Previous studies from our laboratories demonstrated that dietary NaCl supplementation in NaCl-sensitive spontaneously hypertensive rats elevates blood pressure, increases peripheral sympathetic nervous system activity, and depresses endogenous norepinephrine stores and turnover in the anterior hypothalamus. These findings suggest that reduced noradrenergic input to sympathoinhibitory neurons in anterior hypothalamus contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. The current study tested the hypothesis that dietary NaCl supplementation depresses endogenous norepinephrine stores and turnover in anterior hypothalamus of two other NaCl-sensitive models of hypertension, the Dahl salt-sensitive rat and the deoxycorticosterone acetate/NaCl hypertensive rat, thus increasing blood pressure by reducing noradrenergic input to the anterior hypothalamus. Dahl salt-sensitive rats were fed a high (8%) NaCl diet, and deoxycorticosterone acetate/NaCl rats rats drank 1% NaCl solution ad libitum for 2 or 4 weeks. Age-matched Dahl salt-sensitive rats fed a basal 1% NaCl diet and uninephrectomized Sprague-Dawley rats drinking tap water were controls. Regional brain catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Norepinephrine turnover in hypothalamus (anterior, posterior, and ventral regions) and brain stem (pons and medulla) was assessed using the dopamine beta-hydroxylase inhibitor 1-cyclohexyl-2-mercapto-imidazole. High NaCl treatment caused significant elevations in blood pressure in Dahl salt-sensitive and deoxycorticosterone acetate/NaCl rats, but endogenous norepinephrine levels and turnover rates were not significantly different in anterior hypothalamus or any other brain region studied between the NaCl-supplemented and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  18. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  19. Transcription factor CecR (YbiH) regulates a set of genes affecting the sensitivity of Escherichia coli against cefoperazone and chloramphenicol.

    PubMed

    Yamanaka, Yuki; Shimada, Tomohiro; Yamamoto, Kaneyoshi; Ishihama, Akira

    2016-07-01

    Genomic SELEX (systematic evolution of ligands by exponential enrichment) screening was performed for identification of the binding site of YbiH, an as yet uncharacterized TetR-family transcription factor, on the Escherichia coli genome. YbiH was found to be a unique single-target regulator that binds in vitro within the intergenic spacer located between the divergently transcribed ybiH-ybhGFSR and rhlE operons. YbhG is an inner membrane protein and YbhFSR forms a membrane-associated ATP-binding cassette (ABC) transporter while RhlE is a ribosome-associated RNA helicase. Gel shift assay and DNase footprinting analyses indicated one clear binding site of YbiH, including a complete palindromic sequence of AATTAGTT-AACTAATT. An in vivo reporter assay indicated repression of the ybiH operon and activation of the rhlE operon by YbiH. After phenotype microarray screening, YbiH was indicated to confer resistance to chloramphenicol and cefazoline (a first-generation cephalosporin). A systematic survey of the participation of each of the predicted YbiH-regulated genes in the antibiotic sensitivity indicated involvement of the YbhFSR ABC-type transporter in the sensitivity to cefoperazone (a third-generation cephalosporin) and of the membrane protein YbhG in the control of sensitivity to chloramphenicol. Taken together with the growth test in the presence of these two antibiotics and in vitro transcription assay, it was concluded that the hitherto uncharacterized YbiH regulates transcription of both the bidirectional transcription units, the ybiH-ybhGFSR operon and the rhlE gene, which altogether are involved in the control of sensitivity to cefoperazone and chloramphenicol. We thus propose to rename YbiH as CecR (regulator of cefoperazone and chloramphenicol sensitivity). PMID:27112147

  20. Six-year trajectories of post-traumatic stress and severe psychological distress symptoms and associations with timing of trauma exposure, ongoing adversity and sense of injustice: a latent transition analysis of a community cohort in conflict-affected Timor-Leste

    PubMed Central

    Rees, S; Steel, Z; Tam, N; Soares, Z; Soares, C; Silove, DM

    2016-01-01

    Objectives To identify the 6-year trajectories of post-traumatic stress symptoms (PTSS) and psychological distress symptoms, and examine for associations with timing of trauma exposure, ongoing adversity and with the sense of injustice in conflict-affected Timor-Leste. Setting A whole-of-household survey was conducted in 2004 and 2010 in Dili, the capital of Timor-Leste. Participants 1022 adults were followed up over 6 years (retention rate 84.5%). Interviews were conducted by field workers applying measures of traumatic events (TEs), ongoing adversity, a sense of injustice, PTS symptoms and psychological distress. Results Latent transition analysis supported a 3-class longitudinal model (psychological distress, comorbid symptoms and low symptoms). We derived 4 composite trajectories comprising recovery (20.8%), a persisting morbidity trajectory (7.2%), an incident trajectory (37.2%) and a low-symptom trajectory (34.7%). Compared with the low-symptom trajectory, the persistent and incident trajectories reported greater stress arising from poverty and family conflict, higher TE exposure for 2 historical periods, and a sense of injustice for 2 historical periods. The persistent trajectory was unique in reporting greater TE exposure in the Indonesian occupation, whereas the incident trajectory reported greater TE exposure during the later internal conflict that occurred between baseline and follow-up. Compared with the low-symptom trajectory, the incident trajectory reported a greater sense of injustice relating to the periods of the Indonesian occupation and independence. The persistent trajectory was characterised by a sense of injustice relating to the internal conflict and contemporary times. The recovery trajectory was characterised by the absence of these risk factors, the only difference from the low-symptom trajectory being that the former reported a sense of injustice for the period surrounding independence. Conclusions Our findings suggest that the timing

  1. How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance? Study protocol of a prospective pilot study

    PubMed Central

    Zheng, Yanhua; Stener-Victorin, Elisabet; Ng, Ernest H Y; Li, Juan; Wu, Xiaoke; Ma, Hongxia

    2015-01-01

    Introduction Hyperinsulinaemia and insulin resistance (IR) are key features of polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of acupuncture treatment has been investigated in a completed prospective pilot trial (Clinicaltrials.gov: NCT01457209), and acupuncture with electrical stimulation applied to insulin-resistant rats with dihydrotestosterone-induced PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a prospective pilot study to evaluate whether using the same acupuncture treatment protocol given over a longer period of time (6 months) than in the previous pilot trial will improve insulin sensitivity in women with PCOS and IR. Our hypothesis is that acupuncture with combined manual and low-frequency electrical stimulation of the needles will improve insulin sensitivity in women with PCOS and IR. Methods/analysis This is a prospective pilot trial. A total of 112 women with PCOS and IR will be recruited and categorised according to their body mass index (BMI) as normal weight (BMI=18.5−23 kg/m2) or as overweight/obese (BMI>23 kg/m2). Acupuncture will be applied three times per week for 6 months at 30 min per treatment. The primary outcome will be the change in insulin sensitivity before and after 6 months of acupuncture treatment, as measured by an oral glucose tolerance test. Ethics/dissemination Ethical approval of this study has been granted from the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (No. 2013039). Written and informed consent will be obtained from each patient before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal and presented at international congresses. Trial registration numbers NCT02026323 and ChiCTR-OCH-13003921. PMID:25941189

  2. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

  3. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  4. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  5. Cutaneous Adverse Effects of Neurologic Medications.

    PubMed

    Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

    2016-03-01

    Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.

  6. Dietary zinc deficiency affects blood linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio; a sensitive physiological marker of zinc status in vivo (Gallus gallus).

    PubMed

    Reed, Spenser; Qin, Xia; Ran-Ressler, Rinat; Brenna, James Thomas; Glahn, Raymond P; Tako, Elad

    2014-03-20

    Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn⁺ (zinc adequate control, 42.3 μg/g zinc), and Zn⁻ (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn⁺ control versus Zn⁻ group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn⁺ control group (p < 0.05), and hepatic Δ⁶ desaturase was significantly higher in the Zn⁺ group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn⁻ group compared to the Zn⁺ group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation.

  7. Dietary Zinc Deficiency Affects Blood Linoleic Acid: Dihomo-γ-linolenic Acid (LA:DGLA) Ratio; a Sensitive Physiological Marker of Zinc Status in Vivo (Gallus gallus)

    PubMed Central

    Reed, Spenser; Qin, Xia; Ran-Ressler, Rinat; Brenna, James Thomas; Glahn, Raymond P.; Tako, Elad

    2014-01-01

    Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn(+) (zinc adequate control, 42.3 μg/g zinc), and Zn(−) (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn(+) control versus Zn(−) group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn(+) control group (p < 0.05), and hepatic Δ6 desaturase was significantly higher in the Zn(+) group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn(−) group compared to the Zn(+) group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation. PMID:24658588

  8. Arabidopsis 56–Amino Acid Serine Palmitoyltransferase-Interacting Proteins Stimulate Sphingolipid Synthesis, Are Essential, and Affect Mycotoxin Sensitivity[W][OPEN

    PubMed Central

    Kimberlin, Athen N.; Majumder, Saurav; Han, Gongshe; Chen, Ming; Cahoon, Rebecca E.; Stone, Julie M.; Dunn, Teresa M.; Cahoon, Edgar B.

    2013-01-01

    Maintenance of sphingolipid homeostasis is critical for cell growth and programmed cell death (PCD). Serine palmitoyltransferase (SPT), composed of LCB1 and LCB2 subunits, catalyzes the primary regulatory point for sphingolipid synthesis. Small subunits of SPT (ssSPT) that strongly stimulate SPT activity have been identified in mammals, but the role of ssSPT in eukaryotic cells is unclear. Candidate Arabidopsis thaliana ssSPTs, ssSPTa and ssSPTb, were identified and characterized. Expression of these 56–amino acid polypeptides in a Saccharomyces cerevisiae SPT null mutant stimulated SPT activity from the Arabidopsis LCB1/LCB2 heterodimer by >100-fold through physical interaction with LCB1/LCB2. ssSPTa transcripts were more enriched in all organs and >400-fold more abundant in pollen than ssSPTb transcripts. Accordingly, homozygous ssSPTa T-DNA mutants were not recoverable, and 50% nonviable pollen was detected in heterozygous ssspta mutants. Pollen viability was recovered by expression of wild-type ssSPTa or ssSPTb under control of the ssSPTa promoter, indicating ssSPTa and ssSPTb functional redundancy. SPT activity and sensitivity to the PCD-inducing mycotoxin fumonisin B1 (FB1) were increased by ssSPTa overexpression. Conversely, SPT activity and FB1 sensitivity were reduced in ssSPTa RNA interference lines. These results demonstrate that ssSPTs are essential for male gametophytes, are important for FB1 sensitivity, and limit sphingolipid synthesis in planta. PMID:24214397

  9. Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients.

    PubMed

    Milanesi, Elena; Hadar, Adva; Maffioletti, Elisabetta; Werner, Haim; Shomron, Noam; Gennarelli, Massimo; Schulze, Thomas G; Costa, Marta; Del Zompo, Maria; Squassina, Alessio; Gurwitz, David

    2015-07-01

    Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 (IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression has been suggested as a putative biomarker for lithium unresponsiveness. In this study, we examined the in vitro effects of insulin-like growth factor 1 (IGF-1) on lithium sensitivity in lymphoblastoid cell lines (LCLs) from lithium responder (R) and non-responder (NR) bipolar patients. Moreover, we evaluated levels of microRNA let-7c, a small RNA predicted to target IGF1. We found that exogenous IGF-1 added to serum-free media increased lithium sensitivity selectively in LCLs from NR BD patients. However, no significant differences were observed when comparing let-7c expression in LCLs from R vs. NR BD patients. Our data support a key role for IGF-1 in lithium resistance/response in the treatment of bipolar disorder.

  10. Adverse environments: investigating local variation in child growth.

    PubMed

    Moffat, Tina; Galloway, Tracey

    2007-01-01

    Epigenetic and life history approaches to child growth are centered on the relationship between the organism and its environment. However, defining and operationalizing the concept of environment is challenging, in light of the multiple variables that influence growth. Moreover, the concept of adaptation as it applies to child growth is seldom considered in the developed country context. This paper presents a study of children living in three neighborhoods in the City of Hamilton, Ontario, Canada. Two of the communities are considered adverse environments on the basis of low socioeconomic status, and their inner city, industrial location. In contrast to children living in the higher socioeconomic status area, children in these adverse environments display negative growth indicators, i.e., somewhat constrained linear growth in one and risk for overweight and obesity in both. Although both these inner city neighborhoods constitute adverse environments, they differ in ways that have a significant impact on children's growth. We argue for a definition of "adverse environment" that is broadly based, incorporating a range of physical, social, and temporal factors that are highly localized and sensitive to community-level influences on growth and health. As well, we consider whether higher prevalence of overweight and obesity is adaptive in any way to these adverse environments and conclude that they are more likely to be deleterious than adaptive in either the long or short term.

  11. Factors affecting the f × Q product of 3C-SiC microstrings: What is the upper limit for sensitivity?

    NASA Astrophysics Data System (ADS)

    Kermany, Atieh R.; Bennett, James S.; Brawley, George A.; Bowen, Warwick P.; Iacopi, Francesca

    2016-02-01

    The fn × Q (Hz) is a crucial sensitivity parameter for micro-electro-mechanical sensing. We have recently shown a fn × Q product of ˜1012 Hz for microstrings made of cubic silicon carbide on silicon, establishing a new state-of-the-art and opening new frontiers for mass sensing applications. In this work, we analyse the main parameters influencing the frequency and quality factor of silicon carbide microstrings (material properties, microstring geometry, clamping condition, and environmental pressure) and investigate the potential for approaching the theoretical upper limit. We indicate that our previous result is only about a factor 2 lower than the thermoelastic dissipation limit. For fully reaching this upper limit, a substantial reduction of the defects in the silicon carbide thin film would be required, while maintaining a high residual tensile stress in the perfect-clamped strings.

  12. Destruction of IgG anti-A sensitized erythrocytes by mononuclear leucocytes from normal and ABO haemolytic disease affected infants.

    PubMed Central

    Romano, E L; Rossi Devivo, M L; Soyano, A; Linares, J

    1984-01-01

    Studies were undertaken to investigate the antibody-dependent cell-mediated cytotoxicity (ADCC) activity of mononuclear leucocytes (MNL) from cord and healthy adult blood and that from infants with ABO haemolytic disease. The ADCC levels of MNL from both types of newborn blood were found to be higher than that of MNL from adult blood. The extent of ADCC was positively related to the degree of antibody sensitization of the red cells and to the effector cell target cell ratio. The ADCC activity was effected mainly by the adherent cell fraction and could be inhibited by cytochalasin B, hydrocortisone and also by high concentrations (more than 0.5 mg/ml) of non-specific free human IgG. Phagocytosis was also demonstrated to be an important mechanism in the destruction of IgG anti-A coated red cells by the MNL. PMID:6538121

  13. Disruption of the copper efflux pump (CopA) of Serratia marcescens ATCC 274 pleiotropically affects copper sensitivity and production of the tripyrrole secondary metabolite, prodigiosin.

    PubMed

    Williamson, N R; Simonsen, H T; Harris, A K P; Leeper, F J; Salmond, George P C

    2006-02-01

    The prodigiosin biosynthetic gene cluster (pig cluster) of Serratia marcescens ATCC 274 (Sma 274) is flanked by cueR/copA homologues. Inactivation of the copA homologue resulted in an increased sensitivity to copper, confirming that CopA is involved in copper homeostasis in Sma 274. The effect of copper on the biosynthesis of prodigiosin in Sma 274 and the copA mutant strain was investigated. Increased levels of copper were found to reduce prodigiosin production in the wild type Sma 274, but increase production in the copA mutant strain. The physiological implications for CopA mediated prodigiosin production are discussed. We also demonstrate that the gene products of pigB-pigE of Sma 274 are sufficient for the biosynthesis of 2-methyl-3-n-amyl-pyrrole and condensation with 4-methoxy-2,2'-bipyrrole-5-carboxyaldehyde to form prodigiosin, as we have shown for Serratia sp. ATCC 39006.

  14. Availability of N-Methyl-d-Aspartate Receptor Coagonists Affects Cocaine-Induced Conditioned Place Preference and Locomotor Sensitization: Implications for Comorbid Schizophrenia and Substance Abuse

    PubMed Central

    Puhl, Matthew D.; Berg, Alexandra R.; Bechtholt, Anita J.

    2015-01-01

    Schizophrenia is associated with high prevalence of substance abuse. Recent research suggests that dysregulation of N-methyl-d-aspartate receptor (NMDAR) function may play a role in the pathophysiology of both schizophrenia and drug addiction, and thus, may account for this high comorbidity. Our laboratory has developed two transgenic mouse lines that exhibit contrasting NMDAR activity based on the availability of the glycine modulatory site (GMS) agonists d-serine and glycine. Glycine transporter 1 knockdowns (GlyT1+/−) exhibit NMDAR hyperfunction, whereas serine racemase knockouts (SR−/−) exhibit NMDAR hypofunction. We characterized the behavior of these lines in a cocaine-induced (20 mg/kg) conditioned place preference (CPP) and locomotor sensitization paradigm. Compared with wild-type mice, GlyT1+/− mice displayed hastened extinction of CPP and robust cocaine-induced reinstatement. SR−/− mice appeared to immediately “forget” the learned preference, because they did not exhibit cocaine-induced reinstatement and also displayed attenuated locomotor sensitization. Treatment of GlyT1+/− mice with gavestinel (10 mg/kg on day 1; 5 mg/kg on days 2–17), a GMS antagonist, attenuated cocaine-induced CPP and caused them to immediately “forget” the learned preference. Treatment of SR−/− mice with d-serine (300 mg/kg on day 1; 150 mg/kg on days 2–17) to normalize brain levels caused them to avoid the cocaine-paired side of the chamber during extinction. These results highlight NMDAR dysfunction as a possible neural mechanism underlying comorbid schizophrenia and substance abuse. Also, these findings suggest drugs that directly or indirectly activate the NMDAR GMS could be an effective treatment of cocaine abuse. PMID:25788713

  15. A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men.

    PubMed

    Cedernaes, Jonathan; Lampola, Lauri; Axelsson, Emil K; Liethof, Lisanne; Hassanzadeh, Sara; Yeganeh, Adine; Broman, Jan-Erik; Schiöth, Helgi B; Benedict, Christian

    2016-02-01

    The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral satiety signal. Against this background, in the present study 16 men participated in two separate sessions: one night of PSD (4.25 h sleep) versus one night of full sleep (8.5 h sleep). In the morning following each sleep condition, subjects' oral cavities were rinsed with a 1-molar sucrose solution for 45 s, preceded and followed by blood sampling for repeated determination of plasma glucose and serum insulin concentrations (-3, +3, +5, +7, +10 and +20 min). Our main result was that PSD, compared with full sleep, was associated with significantly higher peripheral insulin resistance, as indicated by a higher fasting homeostasis model assessment of insulin resistance index (+16%, P = 0.025). In contrast, no CPIR was observed in any of the two sleep conditions. Our findings indicate that a single night of PSD is already sufficient to impair fasting insulin sensitivity in healthy men. In contrast, brief oral cavity rinsing with sucrose solution did not change serum insulin concentrations, suggesting that a blunted CPIR is an unlikely mechanism through which acute sleep loss causes metabolic perturbations during morning hours in humans. PMID:26361380

  16. Adverse events in healthcare: learning from mistakes.

    PubMed

    Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D

    2015-04-01

    Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety.

  17. Large-Scale Glycomics of Livestock: Discovery of Highly Sensitive Serum Biomarkers Indicating an Environmental Stress Affecting Immune Responses and Productivity of Holstein Dairy Cows.

    PubMed

    Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro

    2015-12-01

    Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity.

  18. IL-21 is a major negative regulator of IRF4-dependent lipolysis affecting Tregs in adipose tissue and systemic insulin sensitivity.

    PubMed

    Fabrizi, Marta; Marchetti, Valentina; Mavilio, Maria; Marino, Arianna; Casagrande, Viviana; Cavalera, Michele; Moreno-Navarrete, Josè Maria; Mezza, Teresa; Sorice, Gian Pio; Fiorentino, Loredana; Menghini, Rossella; Lauro, Renato; Monteleone, Giovanni; Giaccari, Andrea; Fernandez Real, José Manuel; Federici, Massimo

    2014-06-01

    Obesity elicits immune cell infiltration of adipose tissue provoking chronic low-grade inflammation. Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. Since interleukin (IL)-21 plays an important role in inducing and maintaining immune-mediated chronic inflammatory processes and negatively regulates Treg differentiation/activity, we hypothesized that it could play a role in obesity-induced insulin resistance. We found IL-21 and IL-21R mRNA expression upregulated in adipose tissue of high-fat diet (HFD) wild-type (WT) mice and in stromal vascular fraction from human obese subjects in parallel to macrophage and inflammatory markers. Interestingly, a larger infiltration of Treg cells was seen in the adipose tissue of IL-21 knockout (KO) mice compared with WT animals fed both normal diet and HFD. In a context of diet-induced obesity, IL-21 KO mice, compared with WT animals, exhibited lower body weight, improved insulin sensitivity, and decreased adipose and hepatic inflammation. This metabolic phenotype is accompanied by a higher induction of interferon regulatory factor 4 (IRF4), a transcriptional regulator of fasting lipolysis in adipose tissue. Our data suggest that IL-21 exerts negative regulation on IRF4 and Treg activity, developing and maintaining adipose tissue inflammation in the obesity state.

  19. Deletion of PdMit1, a homolog of yeast Csg1, affects growth and Ca(2+) sensitivity of the fungus Penicillium digitatum, but does not alter virulence.

    PubMed

    Zhu, Congyi; Wang, Weili; Wang, Mingshuang; Ruan, Ruoxin; Sun, Xuepeng; He, Meixian; Mao, Cungui; Li, Hongye

    2015-04-01

    GDP-mannose:inositol-phosphorylceramide (MIPC) and its derivatives are important for Ca(2+) sensitization of Saccharomyces cerevisiae and for the virulence of Candida albicans, but its role in the virulence of plant fungal pathogens remains unclear. In this study, we report the identification and functional characterization of PdMit1, the gene encoding MIPC synthase in Penicillium digitatum, one of the most important pathogens of postharvest citrus fruits. To understand the function of PdMit1, a PdMit1 deletion mutant was generated. Compared to its wild-type control, the PdMit1 deletion mutant exhibited slow radial growth, decreased conidia production and delayed conidial germination, suggesting that PdMit1 is important for the growth of mycelium, sporulation and conidial germination. The PdMit1 deletion mutant also showed hypersensitivity to Ca(2+). Treatment with 250 mmol/l Ca(2+) induced vacuole fusion in the wild-type strain, but not in the PdMit1 deletion mutant. Treatment with 250mmol/lCaCl2 upregulated three Ca(2+)-ATPase genes in the wild-type strain, and this was significantly inhibited in the PdMit1 deletion mutant. These results suggest that PdMit1 may have a role in regulating vacuole fusion and expression of Ca(2+)-ATPase genes by controlling biosynthesis of MIPC, and thereby imparts P. digitatum Ca(2+) tolerance. However, we found that PdMit1 is dispensable for virulence of P. digitatum.

  20. Large-Scale Glycomics of Livestock: Discovery of Highly Sensitive Serum Biomarkers Indicating an Environmental Stress Affecting Immune Responses and Productivity of Holstein Dairy Cows.

    PubMed

    Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro

    2015-12-01

    Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity. PMID:26595672

  1. Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.

    PubMed

    Mostad, Ingrid L; Bjerve, Kristian S; Basu, Samar; Sutton, Pauline; Frayn, Keith N; Grill, Valdemar

    2009-12-01

    Fatty acids (FA) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA. Here we tested for acute effects of marine n-3 FA on insulin sensitivity, insulin secretion, energy metabolism, and oxidative stress. This was a randomized, double-blind, crossover study in 11 subjects with type 2 diabetes mellitus. A 4-hour lipid infusion (Intralipid [Fresenius Kabi, Halden, Norway], total of 384 mL) was compared with a similar lipid infusion partly replaced by Omegaven (Fresenius Kabi) that contributed a median of 0.1 g fish oil per kilogram body weight, amounting to 0.04 g/kg of marine n-3 FA. Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps; insulin secretion (measured after the clamps), by C-peptide glucagon tests; and energy metabolism, by indirect calorimetry. Infusion of Omegaven increased the proportion of n-3 FA in plasma nonesterified fatty acids (NEFA) compared with Intralipid alone (20:5n-3: median, 1.5% [interquartile range, 0.6%] vs -0.2% [0.2%], P = .001; 22:6n-3: 0.8% [0.4%] vs -0.7% [0.2%], P = .001). However, glucose utilization was not affected; neither was insulin secretion or total energy production (P = .966, .210, and .423, respectively, for the differences between the lipid clamps). Omegaven tended to lower oxidation of fat (P = .062) compared with Intralipid only, correlating with the rise in individual n-3 NEFA (r = 0.627, P = .039). The effects of clamping on phospholipid FA composition, leptin, adiponectin, or F(2)-isoprostane concentrations were not affected by Omegaven. Enrichment of NEFA with n-3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.

  2. The impact on students of adverse experiences during medical school.

    PubMed

    Wilkinson, Tim J; Gill, Denzil J; Fitzjohn, Julie; Palmer, Claire L; Mulder, Roger T

    2006-03-01

    This study aimed to determine the consequences for, and coping method used by, medical students who experienced adverse experiences during their training. A nationwide questionnaire based census of all current medical students in New Zealand. The response rate was 83% (1384/1660). Two-thirds of students had at least one adverse experience, with humiliation being the most common and having the greatest adverse impact. Unwanted sexual advances, unfair treatment on the basis of gender or race had a lesser impact for most students. Most students took several hours or several days to get over an adverse episode and most commonly they then avoided that person or department. Around one half sought help. Only one-quarter felt it motivated their learning while one-sixth felt it made them consider leaving medical school. The most common perpetrators were senior doctors or nurses. Unwanted sexual advances were most common from other students or from patients. Humiliation is the experience that affected students the most and had a significant adverse effect on learning. There is a disturbing rate of unacceptable practice within medical schools, not all of which is from doctors. PMID:16707293

  3. Reliability of adverse symptom event reporting by clinicians

    PubMed Central

    Li, Yuelin; Coffey, Charles W.; Sit, Laura; Shaw, Mary; Lavene, Dawn; Bennett, Antonia V.; Fruscione, Mike; Rogak, Lauren; Hay, Jennifer; Gönen, Mithat; Schrag, Deborah; Basch, Ethan

    2013-01-01

    Purpose Adverse symptom event reporting is vital as part of clinical trials and drug labeling to ensure patient safety and inform risk–benefit decision making. The purpose of this study was to assess the reliability of adverse event reporting of different clinicians for the same patient for the same visit. Methods A retrospective reliability analysis was completed for a sample of 393 cancer patients (42.8% men; age 26–91, M = 62.39) from lung (n = 134), prostate (n = 113), and Ob/Gyn (n = 146) clinics. These patients were each seen by two clinicians who independently rated seven Common Terminology Criteria for Adverse Events (CTCAE) symptoms. Twenty-three percent of patients were enrolled in therapeutic clinical trials. Results The average time between rater evaluations was 68 min. Intraclass correlation coefficients were moderate for constipation (0.50), diarrhea (0.58), dyspnea (0.69), fatigue (0.50), nausea (0.52), neuropathy (0.71), and vomiting (0.46). These values demonstrated stability over follow-up visits. Two-point differences, which would likely affect treatment decisions, were most frequently seen among symptomatic patients for constipation (18%), vomiting (15%), and nausea (8%). Conclusion Agreement between different clinicians when reporting adverse symptom events is moderate at best. Modification of approaches to adverse symptom reporting, such as patient self-reporting, should be considered. PMID:21984468

  4. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. PMID:27100471

  5. Deletion of PdMit1, a homolog of yeast Csg1, affects growth and Ca2+ sensitivity of the fungus Penicillium digitatum, but does not alter virulence

    PubMed Central

    Zhu, Congyi; Wang, Weili; Wang, Mingshuang; Ruan, Ruoxin; Sun, Xuepeng; He, Meixian; Mao, Cungui; Li, Hongye

    2015-01-01

    GDP-mannose:inositol-phosphorylceramide (MIPC) and its derivatives are important for Ca2+ sensitization of Saccharomyces cerevisiae and for the virulence of Candida albicans, but its role in the virulence of plant fungal pathogens remains unclear. In this study, we report the identification and functional characterization of PdMit1, the gene encoding MIPC synthase in Penicillium digitatum, one of the most important pathogens of postharvest citrus fruits. To understand the function of PdMit1, a PdMit1 deletion mutant was generated. Compared to its wild-type control, the PdMit1 deletion mutant exhibited slow radial growth, decreased conidia production and delayed conidial germination, suggesting that PdMit1 is important for the growth of mycelium, sporulation and conidial germination. The PdMit1 deletion mutant also showed hypersensitivity to Ca2+. Treatment with 250 mmol/l Ca2+ induced vacuole fusion in the wild-type strain, but not in the PdMit1 deletion mutant. Treatment with 250 mmol/lCaCl2 upregulated three Ca2+-ATPase genes in the wild-type strain, and this was significantly inhibited in the PdMit1 deletion mutant. These results suggest that PdMit1 may have a role in regulating vacuole fusion and expression of Ca2+-ATPase genes by controlling biosynthesis of MIPC, and thereby imparts P. digitatum Ca2+ tolerance. However, we found that PdMit1 is dispensable for virulence of P. digitatum. PMID:25725383

  6. Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway

    PubMed Central

    Allache, Redouane; Lachance, Stéphanie; Guyot, Marie Claude; De Marco, Patrizia; Merello, Elisa; Justice, Monica J.; Capra, Valeria; Kibar, Zoha

    2014-01-01

    Wnt signaling has been classified as canonical Wnt/β-catenin-dependent or non-canonical planar cell polarity (PCP) pathway. Misregulation of either pathway is linked mainly to cancer or neural tube defects (NTDs), respectively. Both pathways seem to antagonize each other, and recent studies have implicated a number of molecular switches that activate one pathway while simultaneously inhibiting the other thereby partially mediating this antagonism. The lipoprotein receptor–related protein Lrp6 is crucial for the activation of the Wnt/β-catenin pathway, but its function in Wnt/PCP signaling remains largely unknown. In this study, we investigate the role of Lrp6 as a molecular switch between both Wnt pathways in a novel ENU mouse mutant of Lrp6 (Skax26m1Jus) and in human NTDs. We demonstrate that Skax26m1Jus represents a hypermorphic allele of Lrp6 with increased Wnt canonical and abolished PCP-induced JNK activities. We also show that Lrp6Skax26-Jus genetically interacts with a PCP mutant (Vangl2Lp) where double heterozygotes showed an increased frequency of NTDs and defects in cochlear hair cells’ polarity. Importantly, our study also demonstrates the association of rare and novel missense mutations in LRP6 that is an inhibitor rather than an activator of the PCP pathway with human NTDs. We show that three LRP6 mutations in NTDs led to a reduced Wnt canonical activity and enhanced PCP signaling. Our data confirm an inhibitory role of Lrp6 in PCP signaling in neurulation and indicate the importance of a tightly regulated and highly dosage-sensitive antagonism between both Wnt pathways in this process. PMID:24203697

  7. Exercise hypertension: an adverse prognosis?

    PubMed

    Smith, Ryan G; Rubin, Stanley A; Ellestad, Myrvin H

    2009-01-01

    We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. PMID:20409979

  8. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  9. Antiphase light and temperature cycles affect PHYTOCHROME B-controlled ethylene sensitivity and biosynthesis, limiting leaf movement and growth of Arabidopsis.

    PubMed

    Bours, Ralph; van Zanten, Martijn; Pierik, Ronald; Bouwmeester, Harro; van der Krol, Alexander

    2013-10-01

    In the natural environment, days are generally warmer than the night, resulting in a positive day/night temperature difference (+DIF). Plants have adapted to these conditions, and when exposed to antiphase light and temperature cycles (cold photoperiod/warm night [-DIF]), most species exhibit reduced elongation growth. To study the physiological mechanism of how light and temperature cycles affect plant growth, we used infrared imaging to dissect growth dynamics under +DIF and -DIF in the model plant Arabidopsis (Arabidopsis thaliana). We found that -DIF altered leaf growth patterns, decreasing the amplitude and delaying the phase of leaf movement. Ethylene application restored leaf growth in -DIF conditions, and constitutive ethylene signaling mutants maintain robust leaf movement amplitudes under -DIF, indicating that ethylene signaling becomes limiting under these conditions. In response to -DIF, the phase of ethylene emission advanced 2 h, but total ethylene emission was not reduced. However, expression analysis on members of the 1-aminocyclopropane-1-carboxylic acid (ACC) synthase ethylene biosynthesis gene family showed that ACS2 activity is specifically suppressed in the petiole region under -DIF conditions. Indeed, petioles of plants under -DIF had reduced ACC content, and application of ACC to the petiole restored leaf growth patterns. Moreover, acs2 mutants displayed reduced leaf movement under +DIF, similar to wild-type plants under -DIF. In addition, we demonstrate that the photoreceptor PHYTOCHROME B restricts ethylene biosynthesis and constrains the -DIF-induced phase shift in rhythmic growth. Our findings provide a mechanistic insight into how fluctuating temperature cycles regulate plant growth.

  10. Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands.

    PubMed

    Peng, Hui; Sun, Jianxian; Alharbi, Hattan A; Jones, Paul D; Giesy, John P; Wiseman, Steve

    2016-07-19

    Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025× equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS(1) and MS(2) spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ. PMID:27340905

  11. Antiphase Light and Temperature Cycles Affect PHYTOCHROME B-Controlled Ethylene Sensitivity and Biosynthesis, Limiting Leaf Movement and Growth of Arabidopsis1[C][W

    PubMed Central

    Bours, Ralph; van Zanten, Martijn; Pierik, Ronald; Bouwmeester, Harro; van der Krol, Alexander

    2013-01-01

    In the natural environment, days are generally warmer than the night, resulting in a positive day/night temperature difference (+DIF). Plants have adapted to these conditions, and when exposed to antiphase light and temperature cycles (cold photoperiod/warm night [−DIF]), most species exhibit reduced elongation growth. To study the physiological mechanism of how light and temperature cycles affect plant growth, we used infrared imaging to dissect growth dynamics under +DIF and −DIF in the model plant Arabidopsis (Arabidopsis thaliana). We found that −DIF altered leaf growth patterns, decreasing the amplitude and delaying the phase of leaf movement. Ethylene application restored leaf growth in −DIF conditions, and constitutive ethylene signaling mutants maintain robust leaf movement amplitudes under −DIF, indicating that ethylene signaling becomes limiting under these conditions. In response to −DIF, the phase of ethylene emission advanced 2 h, but total ethylene emission was not reduced. However, expression analysis on members of the 1-aminocyclopropane-1-carboxylic acid (ACC) synthase ethylene biosynthesis gene family showed that ACS2 activity is specifically suppressed in the petiole region under −DIF conditions. Indeed, petioles of plants under −DIF had reduced ACC content, and application of ACC to the petiole restored leaf growth patterns. Moreover, acs2 mutants displayed reduced leaf movement under +DIF, similar to wild-type plants under −DIF. In addition, we demonstrate that the photoreceptor PHYTOCHROME B restricts ethylene biosynthesis and constrains the −DIF-induced phase shift in rhythmic growth. Our findings provide a mechanistic insight into how fluctuating temperature cycles regulate plant growth. PMID:23979970

  12. Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

    SciTech Connect

    Kita, Ayako; Higa, Mari; Doi, Akira; Satoh, Ryosuke; Sugiura, Reiko

    2015-02-13

    Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2{sup +} gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2{sup +} gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking.

  13. Early adversity, neural development, and inflammation.

    PubMed

    Chiang, Jessica J; Taylor, Shelley E; Bower, Julienne E

    2015-12-01

    Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.

  14. [Cutaneous adverse effects of TNFalpha antagonists].

    PubMed

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  15. Changing Medicine and Building Community: Maine’s Adverse Childhood Experiences Momentum

    PubMed Central

    Forstadt, Leslie; Cooper, Sally; Andrews, Sue Mackey

    2015-01-01

    Physicians are instrumental in community education, prevention, and intervention for adverse childhood experiences. In Maine, a statewide effort is focusing on education about adverse childhood experiences and ways that communities and physicians can approach childhood adversity. This article describes how education about adversity and resilience can positively change the practice of medicine and related fields. The Maine Resilience Building Network brings together ongoing programs, supports new ventures, and builds on existing resources to increase its impact. It exemplifies the collective impact model by increasing community knowledge, affecting medical practice, and improving lives. PMID:25902346

  16. Non-enzymatic modifications of prostaglandin H synthase 1 affect bifunctional enzyme activity - Implications for the sensitivity of blood platelets to acetylsalicylic acid.

    PubMed

    Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Stec-Martyna, Emilia; Pawlowska, Zofia; Watala, Cezary

    2016-06-25

    Due to its ability to inhibit the blood platelet PGHS-1, acetylsalicylic acid (ASA, Aspirin(®)) is widely used as a preventive agent in atherothrombotic diseases. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair effective ASA-mediated acetylation process. On the other hand, it is proposed that ASA can prevent some of the late complications of diabetes by lowering the extent of glycation at protein free amino groups. The aim of this work was to evaluate the extents of non-enzymatic N-glycosylation (glycation) and acetylation of blood platelet PGHS-1 (COX-1) and the competition between glycation and acetylation was investigated in order to demonstrate how these two reactions may compete against platelet PGHS-1. When PGHS-1 was incubated with glycating/acetylating agents (glucose, Glu; 1,6-bisphosphofructose, 1,6-BPF; methylglyoxal, MGO, acetylsalicylic acid, ASA), the enzyme was modified in 13.4 ± 1.6, 5.3 ± 0.5, 10.7 ± 1.2 and 6.4 ± 1.1 mol/mol protein, respectively, and its activity was significantly reduced. The prior glycation/carbonylation of PGHS-1 with Glu, 1,6-BPF or MGO decreased the extent of acetylation from 6.4 ± 1.1 down to 2.5 ± 0.2, 3.6 ± 0.3 and 5.2 ± 0.2 mol/mol protein, respectively, but the enzyme still remained susceptible to the subsequent inhibition of its activity with ASA. When PGHS-1 was first acetylated with ASA and then incubated with glycating/carbonylating agents, we observed the following reductions in the enzyme modifications: from 13.4 ± 1.6 to 8.7 ± 0.6 mol/mol protein for Glu, from 5.3 ± 0.5 to 3.9 ± 0.3 mol/mol protein for 1,6-BPF and from 10.7 ± 1.2 to 7.5 ± 0.5 mol/mol protein for MGO, however subsequent glycation/carbonylation did not significantly affect PGHS-1 function. Overall, our outcomes allow to better understand the structural aspects of the chemical competition between glycation and acetylation of PGHS-1

  17. Sensitivity of spectral reflectance values to different burn and vegetation ratios: A multi-scale approach applied in a fire affected area

    NASA Astrophysics Data System (ADS)

    Pleniou, Magdalini; Koutsias, Nikos

    2013-05-01

    The aim of our study was to explore the spectral properties of fire-scorched (burned) and non fire-scorched (vegetation) areas, as well as areas with different burn/vegetation ratios, using a multisource multiresolution satellite data set. A case study was undertaken following a very destructive wildfire that occurred in Parnitha, Greece, July 2007, for which we acquired satellite images from LANDSAT, ASTER, and IKONOS. Additionally, we created spatially degraded satellite data over a range of coarser resolutions using resampling techniques. The panchromatic (1 m) and multispectral component (4 m) of IKONOS were merged using the Gram-Schmidt spectral sharpening method. This very high-resolution imagery served as the basis to estimate the cover percentage of burned areas, bare land and vegetation at pixel level, by applying the maximum likelihood classification algorithm. Finally, multiple linear regression models were fit to estimate each land-cover fraction as a function of surface reflectance values of the original and the spatially degraded satellite images. The main findings of our research were: (a) the Near Infrared (NIR) and Short-wave Infrared (SWIR) are the most important channels to estimate the percentage of burned area, whereas the NIR and red channels are the most important to estimate the percentage of vegetation in fire-affected areas; (b) when the bi-spectral space consists only of NIR and SWIR, then the NIR ground reflectance value plays a more significant role in estimating the percent of burned areas, and the SWIR appears to be more important in estimating the percent of vegetation; and (c) semi-burned areas comprising 45-55% burned area and 45-55% vegetation are spectrally closer to burned areas in the NIR channel, whereas those areas are spectrally closer to vegetation in the SWIR channel. These findings, at least partially, are attributed to the fact that: (i) completely burned pixels present low variance in the NIR and high variance in the

  18. Early adversity and mental health: linking extremely low birth weight, emotion regulation, and internalizing disorders.

    PubMed

    Waxman, Jordana; Van Lieshout, Ryan J; Schmidt, Louis A

    2014-01-01

    The experience of early adversity can increase one's risk of psychopathology later in life. Extremely low birth weight (ELBW) provides a unique model of early adversity that affords us the opportunity to understand how prenatal and early postnatal stressors can affect the development of emotional, biological, and behavioural systems. Since the neuroendocrine system and emotion regulation can both be negatively affected by exposure to early adversity, and dysregulation in these regulatory systems has been linked to various forms of psychopathology, it is possible that these systems could mediate and/or moderate associations between early adversity, specifically ELBW, and later internalizing disorders. In this review, we discuss evidence of an early programming hypothesis underlying psychopathology and the identification of neuroendocrine markers of early adversity that may mediate/moderate the development of psychopathology.

  19. Dietary aspects of adverse reactions to foods in adults.

    PubMed Central

    Parker, S L; Sussman, G L; Krondl, M

    1988-01-01

    Dietary considerations play an important role in the diagnosis, treatment and management of immunologic and nonimmunologic reactions to foods. Food diaries and trial elimination diets may prove helpful in identifying the responsible foods. Elimination diets must be monitored carefully for nutritional adequacy and should be used no longer than absolutely necessary; in some instances appropriate vitamin and mineral supplementation may be necessary. Ideally the identification of foods that provoke symptoms should be confirmed by means of double-blind challenge testing. Avoidance of some problem foods is unlikely to cause nutritional problems, but the practical and nutritional implications of allergies to staple foods such as cow's milk, eggs and wheat are far greater. Nonimmunologic adverse reactions that may mimic food allergic reactions include gastrointestinal disorders, sensitivity to food additives and psychologically based adverse reactions. There may be some degree of tolerance in metabolic disorders, which makes dietary management easier. Sensitivity to food additives necessitates careful scrutiny of food labels. In psychologic adverse reactions to foods, several foods are often involved, which increases the risk of nutritional problems. PMID:3048623

  20. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  1. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  2. Understanding adverse events: human factors.

    PubMed

    Reason, J

    1995-06-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  3. Multiple adverse experiences and child cognitive development.

    PubMed

    Guinosso, Stephanie A; Johnson, Sara B; Riley, Anne W

    2016-01-01

    During childhood and adolescence, children's social environments shape their cognitive development. Children exposed to multiple adversities in their social environment are more likely to have poorer cognitive outcomes. These findings have prompted interest among pediatric and public health communities to screen and connect youth to appropriate interventions that ameliorate the detrimental effects of adverse exposures. Such intervention efforts can be improved with a stronger conceptual understanding of the relationship between multiple adverse exposures and child cognitive development. This includes disentangling adverse exposures from other risk factors or underlying mechanisms, specifying mechanisms of action, and determining when adverse exposures are most detrimental. This review summarizes findings from the literature on each of these areas and proposes a conceptual model to guide further research and intervention.

  4. Adverse effects of anabolic steroids in athletes.

    PubMed

    Kibble, M W; Ross, M B

    1987-09-01

    The effects of anabolic steroid use on athletic performance and the adverse effects associated with the use of anabolic steroids are reviewed. Anabolic steroids increase protein synthesis in skeletal muscles and reverse catabolic processes. Because of these properties, some athletes use anabolic steroids in an attempt to improve their athletic performance. However, studies indicate that increases in muscle mass and strength during anabolic steroid administration are observed only in athletes who already are weight-trained and who continue intensive training while maintaining high-protein, high-calorie diets. Adverse effects attributed to anabolic steroid use occur frequently. Serious adverse effects include hepatic and endocrine dysfunction; cardiovascular and behavioral changes also are reported. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women. The use of anabolic steroids to improve athletic performance has become prevalent. However, the reported benefits are tempered by numerous adverse reactions.

  5. Adulthood personality correlates of childhood adversity

    PubMed Central

    Carver, Charles S.; Johnson, Sheri L.; McCullough, Michael E.; Forster, Daniel E.; Joormann, Jutta

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which we termed anger/aggression, extrinsic focus, agreeableness, and engagement. Results: Controlling for concurrent depressive symptoms and gender, higher levels of reported childhood adversity related to lower agreeableness and to higher anger/aggression and extrinsic focus. Conclusions: Findings suggest that early adversity is linked to personality variables relevant to the building of social connection. PMID:25484874

  6. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  7. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

    PubMed

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

    2016-04-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.

  8. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

    PubMed

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

    2016-04-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

  9. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament

    PubMed Central

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A.; Münsterkötter, Anna L.; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter

    2016-01-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

  10. Adverse Effects of Wheat Gluten.

    PubMed

    Koning, Frits

    2015-01-01

    Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet.

  11. Adverse Effects of Wheat Gluten.

    PubMed

    Koning, Frits

    2015-01-01

    Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet. PMID:26606684

  12. Adverse childhood event experiences, fertility difficulties, and menstrual cycle characteristics

    PubMed Central

    Jacobs, Marni B.; Boynton-Jarrett, Renee D.; Harville, Emily W.

    2016-01-01

    Introduction Increased childhood adversity may be affect adult fertility, however, the mechanism through which this occurs is unclear. Menstrual cycle abnormalities are predictive of fertility difficulties, and stress influences menstrual cycle characteristics. Here, we assesses whether adverse childhood experiences (ACEs) are associated with fertility difficulties and menstrual cycle dysregulation, offering a plausible mechanism for the link between lifetime stress and fertility. Methods From April 2012 – February 2014, 742 pregnant and non-pregnant women aged 18–45 years residing in southeastern Louisiana provided information on childhood adversity and reproductive history. Associations between ACEs and fertility difficulties and menstrual cycle patterns were evaluated. Results As the number of ACEs increased, risk of fertility difficulties and amenorrhea increased (RR = 1.09, 95% CI 1.05 – 1.13 and RR = 1.07, 95% CI 1.04 – 1.10, respectively), while fecundability decreased (FR = 0.97, 95% CI 0.95 – 1.00). Compared to women with no adversity, women in the high adversity group were more likely to experience both infertility and amenorrhea (RR = 2.75, 95% CI 1.45 – 5.21 and RR = 2.54, 95% CI 1.52 – 4.25, respectively), and reduced fecundability (FR = 0.75, 95% CI 0.56 – 1.00). Although similar patterns were seen for menstrual cycle irregularity, associations were diminished. Associations did not materially change following adjustment for age, BMI, race, education, smoking, and income. Results are constrained by the self-report nature of the study and the limited generalizability of the study population. Discussion To our knowledge, this is the first study to present evidence of a link between childhood stressors, menstrual cycle disruption, and fertility difficulties. The effect of childhood stress on fertility may be mediated through altered functioning of the HPA axis, acting to suppress fertility in response to less than optimal reproductive

  13. Chemical research on red pigments after adverse reactions to tattoo.

    PubMed

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

    2016-03-01

    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition. PMID:26934738

  14. Uncertainty Comparison of Visual Sensing in Adverse Weather Conditions.

    PubMed

    Lo, Shi-Wei; Wu, Jyh-Horng; Chen, Lun-Chi; Tseng, Chien-Hao; Lin, Fang-Pang; Hsu, Ching-Han

    2016-01-01

    This paper focuses on flood-region detection using monitoring images. However, adverse weather affects the outcome of image segmentation methods. In this paper, we present an experimental comparison of an outdoor visual sensing system using region-growing methods with two different growing rules-namely, GrowCut and RegGro. For each growing rule, several tests on adverse weather and lens-stained scenes were performed, taking into account and analyzing different weather conditions with the outdoor visual sensing system. The influence of several weather conditions was analyzed, highlighting their effect on the outdoor visual sensing system with different growing rules. Furthermore, experimental errors and uncertainties obtained with the growing rules were compared. The segmentation accuracy of flood regions yielded by the GrowCut, RegGro, and hybrid methods was 75%, 85%, and 87.7%, respectively. PMID:27447642

  15. Uncertainty Comparison of Visual Sensing in Adverse Weather Conditions†

    PubMed Central

    Lo, Shi-Wei; Wu, Jyh-Horng; Chen, Lun-Chi; Tseng, Chien-Hao; Lin, Fang-Pang; Hsu, Ching-Han

    2016-01-01

    This paper focuses on flood-region detection using monitoring images. However, adverse weather affects the outcome of image segmentation methods. In this paper, we present an experimental comparison of an outdoor visual sensing system using region-growing methods with two different growing rules—namely, GrowCut and RegGro. For each growing rule, several tests on adverse weather and lens-stained scenes were performed, taking into account and analyzing different weather conditions with the outdoor visual sensing system. The influence of several weather conditions was analyzed, highlighting their effect on the outdoor visual sensing system with different growing rules. Furthermore, experimental errors and uncertainties obtained with the growing rules were compared. The segmentation accuracy of flood regions yielded by the GrowCut, RegGro, and hybrid methods was 75%, 85%, and 87.7%, respectively. PMID:27447642

  16. Mechanisms and assessment of statin-related muscular adverse effects.

    PubMed

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-09-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

  17. Chemical research on red pigments after adverse reactions to tattoo.

    PubMed

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

    2016-03-01

    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition.

  18. Impact of early life adversity on EMG stress reactivity of the trapezius muscle.

    PubMed

    Luijcks, Rosan; Vossen, Catherine J; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J; Lousberg, Richel

    2016-09-01

    Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies. PMID:27684800

  19. Childhood adversities and psychosis: evidence, challenges, implications

    PubMed Central

    Morgan, Craig; Gayer‐Anderson, Charlotte

    2016-01-01

    There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID:27265690

  20. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  1. Encouraging spontaneous reporting of adverse effects.

    PubMed

    2015-02-01

    One priority when organising surveillance of health products is to remove barriers to reporting adverse effects. One way to encourage reporting is by providing regular feedback, as practised by the German drug bulletin arznei-telegramm, for example. PMID:25802925

  2. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  3. Gluten Sensitivity.

    PubMed

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on

  4. Gluten Sensitivity.

    PubMed

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on

  5. Affective Dynamics in Psychopathology

    PubMed Central

    Trull, Timothy J.; Lane, Sean P.; Koval, Peter; Ebner-Priemer, Ulrich W.

    2016-01-01

    We discuss three varieties of affective dynamics (affective instability, emotional inertia, and emotional differentiation). In each case, we suggest how these affective dynamics should be operationalized and measured in daily life using time-intensive methods, like ecological momentary assessment or ambulatory assessment, and recommend time-sensitive analyses that take into account not only the variability but also the temporal dependency of reports. Studies that explore how these affective dynamics are associated with psychological disorders and symptoms are reviewed, and we emphasize that these affective processes are within a nexus of other components of emotion regulation.

  6. Additive Contributions of Childhood Adversity and Recent Stressors to Inflammation at Midlife: Findings from the MIDUS Study

    ERIC Educational Resources Information Center

    Hostinar, Camelia E.; Lachman, Margie E.; Mroczek, Daniel K.; Seeman, Teresa E.; Miller, Gregory E.

    2015-01-01

    We examined the joint contributions of self-reported adverse childhood experiences (ACEs) and recent life events (RLEs) to inflammation at midlife, by testing 3 competing theoretical models: stress generation, stress accumulation, and early life stress sensitization. We aimed to identify potential mediators between adversity and inflammation.…

  7. Are Psychopaths Morally Sensitive?

    ERIC Educational Resources Information Center

    Maxwell, Bruce; Le Sage, Leonie

    2009-01-01

    Philosophical and psychological opinion is divided over whether moral sensitivity, understood as the ability to pick out a situation's morally salient features, necessarily involves emotional engagement. This paper seeks to offer insight into this question. It reasons that if moral sensitivity does draw significantly on affective capacities of…

  8. Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases

    PubMed Central

    Nomura, Kaori; Takahashi, Kunihiko; Hinomura, Yasushi; Kawaguchi, Genta; Matsushita, Yasuyuki; Marui, Hiroko; Anzai, Tatsuhiko; Hashiguchi, Masayuki; Mochizuki, Mayumi

    2015-01-01

    Background The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection. Methods Two AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems. Results The two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.6±1.3 (maximum 37) in the JP and 3.3±3.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected. Conclusion The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data. PMID:26109846

  9. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... facility uses cooling water withdrawn from a freshwater river or stream and the design intake flow of your... affect the management of fisheries. In determining whether any such disruption does not adversely affect the management of fisheries, you must consult with Federal, State, or Tribal fish and...

  10. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... facility uses cooling water withdrawn from a freshwater river or stream and the design intake flow of your... affect the management of fisheries. In determining whether any such disruption does not adversely affect the management of fisheries, you must consult with Federal, State, or Tribal fish and...

  11. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... facility uses cooling water withdrawn from a freshwater river or stream and the design intake flow of your... affect the management of fisheries. In determining whether any such disruption does not adversely affect the management of fisheries, you must consult with Federal, State, or Tribal fish and...

  12. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... facility uses cooling water withdrawn from a freshwater river or stream and the design intake flow of your... affect the management of fisheries. In determining whether any such disruption does not adversely affect the management of fisheries, you must consult with Federal, State, or Tribal fish and...

  13. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... facility uses cooling water withdrawn from a freshwater river or stream and the design intake flow of your... affect the management of fisheries. In determining whether any such disruption does not adversely affect the management of fisheries, you must consult with Federal, State, or Tribal fish and...

  14. Developing robust crop plants for sustaining growth and yield under adverse climatic changes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural production and quality are expected to suffer from adverse changes in climatic conditions, including global warming, and this will affect worldwide human and animal food security. Global warming has been shown to negatively impact crop yield and therefore will affect sustainability of a...

  15. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

  16. [Structural sensitivity analysis].

    PubMed

    Carrera-Hueso, F J; Ramón-Barrios, A

    2011-05-01

    The aim of this study was to perform a structural sensitivity analysis of a decision model and to identify its advantages and limitations. A previously published model of dinoprostone was modified, taking two scenarios into account: eliminating postpartum hemorrhages and including both hemorrhages and uterine hyperstimulation among the adverse effects. The result of the structural sensitivity analysis shows the robustness of the underlying model and confirmed the initial results: the intrauterine device is more cost-effective than intracervical dinoprostone gel. Structural sensitivity analyses should be congruent with the situation studied and clinically validated. Although uncertainty may be only slightly reduced, these analyses provide information and add greater validity and reliability to the model.

  17. Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

    PubMed Central

    Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

    2013-01-01

    Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

  18. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

    Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

    2015-01-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  19. Putative adverse outcome pathways relevant to neurotoxicity

    PubMed Central

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  20. The complement system and adverse pregnancy outcomes.

    PubMed

    Regal, Jean F; Gilbert, Jeffrey S; Burwick, Richard M

    2015-09-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child.

  1. Ocular surface adverse effects of ambient levels of air pollution.

    PubMed

    Torricelli, André Augusto Miranda; Novaes, Priscila; Matsuda, Monique; Alves, Milton Ruiz; Monteiro, Mário Luiz Ribeiro

    2011-01-01

    It is widely recognized today that outdoor air pollution can affect human health. Various chemical components that are present in ambient pollution may have an irritant effect on the mucous membranes of the body, particularly those of the respiratory tract. Much less attention has been focused on the adverse effect on the ocular surface, despite the fact that this structure is even more exposed to air pollution than the respiratory mucosa since only a very thin tear film separates the corneal and conjunctival epithelia from the air pollutants. So far, clinical data are the more widespread tools used by ophthalmologists for assessing possible aggression to the ocular surface; however, clinical findings alone appears not to correlate properly with the complaints presented by the patients pointing out the need for further clinical and laboratory studies on the subject. The purpose of this study is to review signs and symptoms associated with chronic long-term exposure to environmental air pollutants on the ocular structures currently defined as the ocular surface and to review clinical and laboratory tests used to investigate the adverse effects of air pollutants on such structures. We also review previous studies that investigated the adverse effects of air pollution on the ocular surface and discuss the need for further investigation on the subject.

  2. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    PubMed Central

    Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A

    2016-01-01

    Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045

  3. Evaluating a Skin Sensitization Model and Examining Common Assumptions of Skin Sensitizers (ASCCT meeting)

    EPA Science Inventory

    Skin sensitization is an adverse outcome that has been well studied over many decades. It was summarized using the adverse outcome pathway (AOP) framework as part of the OECD work programme (OECD, 2012). Currently there is a strong focus on how AOPs can be applied for different r...

  4. Evaluating a Skin Sensitization Model and Examining Common Assumptions of Skin Sensitizers (QSAR conference)

    EPA Science Inventory

    Skin sensitization is an adverse outcome that has been well studied over many decades. Knowledge of the mechanism of action was recently summarized using the Adverse Outcome Pathway (AOP) framework as part of the OECD work programme (OECD, 2012). Currently there is a strong focus...

  5. Adverse reaction; patent blue turning patient blue.

    PubMed

    Joshi, Meera; Hart, Matthew; Ahmed, Farid; McPherson, Sandy

    2012-11-30

    The authors report a severe anaphylactic reaction to Patent Blue V dye used in sentinel node biopsy for lymphatic mapping during breast cancer surgery to stage the axilla. Patent Blue dye is the most widely used in the UK; however, adverse reactions have been reported with the blue dye previously. This case highlights that reactions may not always be immediately evident and to be vigilant in all patients that have undergone procedures using blue dye. If the patients are not responding appropriately particularly during an anaesthetic, one must always think of a possible adverse reaction to the dye. All surgical patients should give consent for adverse reactions to patent blue dye preoperatively. Alternative agents such as methylene blue are considered.

  6. The multisystem adverse effects of NSAID therapy.

    PubMed

    James, D S

    1999-11-01

    The clinical utility of nonsteroidal anti-inflammatory drugs (NSAIDs) to manage pain and inflammation is limited by adverse side effects. Although effective analgesic and anti-inflammatory agents, NSAIDs are associated with side effects that are a consequence of nonspecific inhibition of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The primary adverse events associated with NSAID therapy are upper gastrointestinal (GI) ulceration, perforation, or bleeding, all of which involve mucosal damage of varying severity and can be asymptomatic and occur with little warning. Clinicians who prescribe NSAIDs should be able to identify patients who are at risk of an NSAID-induced GI adverse event and to detect and manage the event should one occur. The use of COX-2-specific inhibitors to manage pain and inflammation may minimize the risks of NSAID-associated toxicities.

  7. Adverse events related to blood transfusion

    PubMed Central

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-01-01

    The acute blood transfusion reactions are responsible for causing most serious adverse events. Awareness about various clinical features of acute and delayed transfusion reactions with an ability to assess the serious reactions on time can lead to a better prognosis. Evidence-based medicine has changed today's scenario of clinical practice to decrease adverse transfusion reactions. New evidence-based algorithms of transfusion and improved haemovigilance lead to avoidance of unnecessary transfusions perioperatively. The recognition of adverse events under anaesthesia is always challenging. The unnecessary blood transfusions can be avoided with better blood conservation techniques during surgery and with anaesthesia techniques that reduce blood loss. Better and newer blood screening methods have decreased the infectious complications to almost negligible levels. With universal leukoreduction of red blood cells (RBCs), selection of potential donors such as use of male donors only plasma and restriction of RBC storage, most of the non-infectious complications can be avoided. PMID:25535415

  8. Adverse health consequences of the Iraq War.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2013-03-16

    The adverse health consequences of the Iraq War (2003-11) were profound. We conclude that at least 116,903 Iraqi non-combatants and more than 4800 coalition military personnel died over the 8-year course. Many Iraqi civilians were injured or became ill because of damage to the health-supporting infrastructure of the country, and about 5 million were displaced. More than 31,000 US military personnel were injured and a substantial percentage of those deployed suffered post-traumatic stress disorder, traumatic brain injury, and other neuropsychological disorders and their concomitant psychosocial problems. Many family members of military personnel had psychological problems. Further review of the adverse health consequences of this war could help to minimise the adverse health consequences of, and help to prevent, future wars.

  9. Identifying Adverse Drug Events by Relational Learning.

    PubMed

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2012-07-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task, related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events. PMID:24955289

  10. Adverse human health effects associated with molds in the indoor environment.

    PubMed

    Hardin, Bryan D; Kelman, Bruce J; Saxon, Andrew

    2003-05-01

    Molds are common and important allergens. About 5% of individuals are predicted to have some allergic airway symptoms from molds over their lifetime. However, it should be remembered that molds are not dominant allergens and that the outdoor molds, rather than indoor ones, are the most important. For almost all allergic individuals, the reactions will be limited to rhinitis or asthma; sinusitis may occur secondarily due to obstruction. Rarely do sensitized individuals develop uncommon conditions such as ABPA or AFS. To reduce the risk of developing or exacerbating allergies, mold should not be allowed to grow unchecked indoors. When mold colonization is discovered in the home, school, or office, it should be remediated after the source of the moisture that supports its growth is identified and eliminated. Authoritative guidelines for mold remediation are available. Fungi are rarely significant pathogens for humans. Superficial fungal infections of the skin and nails are relatively common in normal individuals, but those infections are readily treated and generally resolve without complication. Fungal infections of deeper tissues are rare and in general are limited to persons with severely impaired immune systems. The leading pathogenic fungi for persons with nonimpaired immune function, Blastomyces, Coccidioides, Cryptococcus, and Histoplasma, may find their way indoors with outdoor air but normally do not grow or propagate indoors. Due to the ubiquity of fungi in the environment, it is not possible to prevent immunecompromised individuals from being exposed to molds and fungi outside the confines of hospital isolation units. Some molds that propagate indoors may under some conditions produce mycotoxins that can adversely affect living cells and organisms by a variety of mechanisms. Adverse effects of molds and mycotoxins have been recognized for centuries following ingestion of contaminated foods. Occupational diseases are also recognized in association with

  11. Fertilizers and Mixed Crop Cultivation of Chromium Tolerant and Sensitive Plants under Chromium Toxicity.

    PubMed

    Dheeba, B; Sampathkumar, P; Kannan, K

    2015-01-01

    Zea mays (maize) and Vigna radiata (green gram) are found to be the chromium (Cr) tolerant and sensitive plants, respectively. In the present paper, we investigate the reduction of the toxicity of Cr in the sensitive plants by the mixed crop cultivation in the field using various amendments. Further, the potassium dichromate was used as the source of hexavalent Cr. The results indicated that Cr adversely affects both the growth and yield of plants. The soil properties vary with Cr and different fertilizer amendments and the yield of both plants were affected by Cr. We conclude that metal accumulation of seeds of green gram was higher than corn and the application of single fertilizer either farm yard manure (FYM) or nitrogen, phosphorous, and potassium (NPK) enhances the growth and yield of both the tolerant and sensitive plants in the mixed crop cultivations. PMID:25709647

  12. Fertilizers and Mixed Crop Cultivation of Chromium Tolerant and Sensitive Plants under Chromium Toxicity

    PubMed Central

    Dheeba, B.; Sampathkumar, P.; Kannan, K.

    2015-01-01

    Zea mays (maize) and Vigna radiata (green gram) are found to be the chromium (Cr) tolerant and sensitive plants, respectively. In the present paper, we investigate the reduction of the toxicity of Cr in the sensitive plants by the mixed crop cultivation in the field using various amendments. Further, the potassium dichromate was used as the source of hexavalent Cr. The results indicated that Cr adversely affects both the growth and yield of plants. The soil properties vary with Cr and different fertilizer amendments and the yield of both plants were affected by Cr. We conclude that metal accumulation of seeds of green gram was higher than corn and the application of single fertilizer either farm yard manure (FYM) or nitrogen, phosphorous, and potassium (NPK) enhances the growth and yield of both the tolerant and sensitive plants in the mixed crop cultivations. PMID:25709647

  13. Active Hemovigilance Significantly Improves Reporting of Acute Non-infectious Adverse Reactions to Blood Transfusion.

    PubMed

    Agnihotri, Naveen; Agnihotri, Ajju

    2016-09-01

    One of the key purposes of a hemovigilance program is to improve reporting of transfusion related adverse events and subsequent data-driven improvement in blood transfusion (BT) practices. We conducted a study over 3 years to assess the impact of healthcare worker training and an active feedback programme on reporting of adverse reactions to BTs. All hospitalized patients who required a BT were included in the study. Healthcare workers involved in BT to patients were sensitized and trained in adverse reaction reporting by conducting training sessions and meetings. All the transfused patients were 'actively' monitored for any acute adverse reaction by using a uniquely coded blood issue form. A total of 18,914 blood components transfused to 5785 different patients resulted in 61 adverse reaction episodes. This incidence of 0.32 % in our study was found to be significantly higher (p < 0.005) than that reported from the same region in the past. Red blood cell units were the most frequently transfused component and thus most commonly involved in an adverse reaction (42.6 %), however apheresis platelets had the highest chance of reaction per unit transfused (0.66 %). There was no mortality associated with the BT during the study period. An active surveillance program significantly improves reporting and management of adverse reactions to BTs. PMID:27429527

  14. Transient Adverse Side Effects During Neurofeedback Training: A Randomized, Sham-Controlled, Double Blind Study.

    PubMed

    Rogel, Ainat; Guez, Jonathan; Getter, Nir; Keha, Eldad; Cohen, Tzlil; Amor, Tali; Todder, Doron

    2015-09-01

    The benefits of clinical neurofeedback training are well known, however, its adverse side-effects are less studied. This research focuses on the transient adverse side effects of neurofeedback training via a double-blind, sham/controlled methodology. Thirty healthy undergraduate students volunteers were randomly divided into three treatment groups: increasing a modified Sensory Motor Rhythm, increasing Upper Alpha, and Sham/control group who receive a random reward. The training sessions were administered for a total of ten sessions. Questionnaires of transient adverse side effects were completed by all volunteers before each session. The results suggest that similar to most medical treatments, neurofeedback can cause transient adverse side effects. Moreover, most participants reported experiencing some side effects. The side effects can be divided into non-specific side effect, associated with the neurofeedback training in general and specific ones associated with the particular protocol. Sensory Motor Rhythm protocol seems to be the most sensitive to side effects.

  15. Submandibular gland tumors. Adverse histologic factors and therapeutic implications.

    PubMed

    Weber, R S; Byers, R M; Petit, B; Wolf, P; Ang, K; Luna, M

    1990-09-01

    We reviewed our 41-year experience with tumors of the submandibular gland to determine what factors influence outcome and their implications for treatment. The most common benign neoplasm was pleomorphic adenoma (21), while among malignant tumors the adenoid cystic variety (37) predominated. For the 86 patients who had malignant tumors, the 2- and 5-year survivals by the life table method were 82% and 69%, respectively. For patients with malignant tumors, histology, size, perineural invasion, and prior treatment did not affect overall survival. Factors adversely affecting outcome were extraglandular soft-tissue extension and lymph node metastasis. Local-regional control was enhanced in patients with soft-tissue extension if they were treated by surgery followed by radiotherapy rather than by surgery alone.

  16. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  17. The adverse outcome pathway knowledge base

    EPA Science Inventory

    The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

  18. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

  19. Adverse Effects of Common Drugs: Dietary Supplements.

    PubMed

    Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

    2015-09-01

    Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists.

  20. Reducing Adverse Impact: One City's Efforts.

    ERIC Educational Resources Information Center

    Prewitt, Jeff

    Following a workshop on "Innovations in Employment Testing that Improve Validity and Reduce Adverse Impact," the City of Louisville (Kentucky) implemented a strategy to develop a comprehensive testing and recruiting program for police recruits. To improve candidate expectations and preparation, the following activities were undertaken: intense…

  1. Helping Student Teachers Avoid Adverse Legal Actions.

    ERIC Educational Resources Information Center

    Peach, Larry; Reddick, Thomas L.

    1984-01-01

    Discusses five areas of the school environment lending themselves to the possibility of teacher and student teacher liability: negligence, malpractice, rights to privacy, field trips, and search of students and school property. Suggests specific guidelines for decreasing the possibility of adverse legal action. (NEC)

  2. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options.

  3. Resilience in the Face of Adversity.

    ERIC Educational Resources Information Center

    Patterson, Jerry

    2001-01-01

    "Resilience" is the capacity for moving ahead under adverse circumstances. School superintendents are advised to stay upbeat and mindful of "both-and" opportunities; stay focused on what they care about; remain flexible and tolerant of ambiguity; be proactive, not reactive; and apply resilience-conserving strategies during tough times. (MLH)

  4. Adverse Effects of Psychotropic Medications on Sleep.

    PubMed

    Doghramji, Karl; Jangro, William C

    2016-09-01

    Psychotropic medications such as antidepressants, antipsychotics, stimulants, and benzodiazepines are widely prescribed. Most of these medications are thought to exert their effects through modulation of various monoamines as well as interactions with receptors such as histamine and muscarinic cholinergic receptors. Through these interactions, psychotropics can also have a significant impact on sleep physiology, resulting in both beneficial and adverse effects on sleep. PMID:27514301

  5. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

    Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues.

  6. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options. PMID:25536126

  7. Potassium fertilization mitigates the adverse effects of drought on selected Zea mays cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present study, the role of potassium (K) in mitigating the adverse effects of drought stress (DS) on 2 maize (Zea mays L.) cultivars, ‘Shaandan 9’ (S9; drought-tolerant) and ‘Shaandan 911’ (S911; drought-sensitive), was assessed. K application increased dry matter (DM) across all growth stage...

  8. Prediction of drug-related cardiac adverse effects in humans--B: use of QSAR programs for early detection of drug-induced cardiac toxicities.

    PubMed

    Frid, Anna A; Matthews, Edwin J

    2010-04-01

    This report describes the use of three quantitative structure-activity relationship (QSAR) programs to predict drug-related cardiac adverse effects (AEs), BioEpisteme, MC4PC, and Leadscope Predictive Data Miner. QSAR models were constructed for 9 cardiac AE clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes) and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). The models were based on a database of post-marketing AEs linked to 1632 chemical structures, and identical training data sets were configured for three QSAR programs. Model performance was optimized and shown to be affected by the ratio of the number of active to inactive drugs. Results revealed that the three programs were complementary and predictive performances using any single positive, consensus two positives, or consensus three positives were as follows, respectively: 70.7%, 91.7%, and 98.0% specificity; 74.7%, 47.2%, and 21.0% sensitivity; and 138.2, 206.3, and 144.2 chi(2). In addition, a prospective study using AE data from the U.S. Food and Drug Administration's (FDA's) MedWatch Program showed 82.4% specificity and 94.3% sensitivity. Furthermore, an external validation study of 18 drugs with serious cardiotoxicity not considered in the models had 88.9% sensitivity. PMID:19941924

  9. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  10. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  11. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  12. Close Friends' Psychopathology as a Pathway From Early Adversity to Young Adulthood Depressive Symptoms.

    PubMed

    Raposa, Elizabeth B; Hammen, Constance L; Brennan, Patricia A

    2015-01-01

    Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults' close friends' psychological symptoms and the impact of these close friendships on later depressive symptoms. A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants' mothers provided contemporaneous information about adversity exposure up to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20s. Youth also nominated a best friend to complete questionnaires about his or her own psychopathology at age 20. Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends' psychopathology predicted target youth depressive symptoms 2 to 5 years later. Results indicate that early adversity continues to affect social functioning throughout young adulthood and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity.

  13. Adverse events in emerging adulthood are associated with increases in neuroticism.

    PubMed

    Boals, Adriel; Southard-Dobbs, Shana; Blumenthal, Heidemarie

    2015-04-01

    Previous studies have produced mixed results when examining whether experiencing an adverse event can lead to changes in Neuroticism. We sought to examine this effect when (a) the event was relatively recent, (b) the event occurred during a relatively early development stage (i.e., emerging adulthood), and (c) the event was severely adverse. A sample of 1,108 undergraduates completed three measures of Neuroticism twice, separated by approximately 3 months, and indicated the most traumatic or adverse event they experienced during the intervening 3 months. We examined two operationalizations of adverse events: one that is more objectively defined (indicated experiencing a trauma listed on a trauma history measure) and another more subjectively defined (participant ratings of event centrality). The results revealed that high Neuroticism at Time 1 predicted future exposure to both types of adverse events. Critically, participants who experienced either type of adverse event during the semester reported significant increases in Neuroticism. Experiencing a high event centrality event was also associated with small increases in the personality traits Openness to Experience and Conscientiousness. The results are discussed in terms of the conditions necessary for adverse events to affect personality traits.

  14. Species sensitivity analysis of heavy metals to freshwater organisms.

    PubMed

    Xin, Zheng; Wenchao, Zang; Zhenguang, Yan; Yiguo, Hong; Zhengtao, Liu; Xianliang, Yi; Xiaonan, Wang; Tingting, Liu; Liming, Zhou

    2015-10-01

    Acute toxicity data of six heavy metals [Cu, Hg, Cd, Cr(VI), Pb, Zn] to aquatic organisms were collected and screened. Species sensitivity distributions (SSD) curves of vertebrate and invertebrate were constructed by log-logistic model separately. The comprehensive comparisons of the sensitivities of different trophic species to six typical heavy metals were performed. The results indicated invertebrate taxa to each heavy metal exhibited higher sensitivity than vertebrates. However, with respect to the same taxa species, Cu had the most adverse effect on vertebrate, followed by Hg, Cd, Zn and Cr. When datasets from all species were included, Cu and Hg were still more toxic than the others. In particular, the toxicities of Pb to vertebrate and fish were complicated as the SSD curves of Pb intersected with those of other heavy metals, while the SSD curves of Pb constructed by total species no longer crossed with others. The hazardous concentrations for 5 % of the species (HC5) affected were derived to determine the concentration protecting 95 % of species. The HC5 values of the six heavy metals were in the descending order: Zn > Pb > Cr > Cd > Hg > Cu, indicating toxicities in opposite order. Moreover, potential affected fractions were calculated to assess the ecological risks of different heavy metals at certain concentrations of the selected heavy metals. Evaluations of sensitivities of the species at various trophic levels and toxicity analysis of heavy metals are necessary prior to derivation of water quality criteria and the further environmental protection.

  15. Interventions to prevent adverse fetal programming due to maternal obesity during pregnancy.

    PubMed

    Nathanielsz, Peter W; Ford, Stephen P; Long, Nathan M; Vega, Claudia C; Reyes-Castro, Luis A; Zambrano, Elena

    2013-10-01

    Maternal obesity is a global epidemic affecting both developed and developing countries. Human and animal studies indicate that maternal obesity adversely programs the development of offspring, predisposing them to chronic diseases later in life. Several mechanisms act together to produce these adverse health effects. There is a consequent need for effective interventions that can be used in the management of human pregnancy to prevent these outcomes. The present review analyzes the dietary and exercise intervention studies performed to date in both altricial and precocial animals, rats and sheep, with the aim of preventing adverse offspring outcomes. The results of these interventions present exciting opportunities to prevent, at least in part, adverse metabolic and other outcomes in obese mothers and their offspring.

  16. Automated identification of adverse events related to central venous catheters.

    PubMed

    Penz, Janet F E; Wilcox, Adam B; Hurdle, John F

    2007-04-01

    Methods for surveillance of adverse events (AEs) in clinical settings are limited by cost, technology, and appropriate data availability. In this study, two methods for semi-automated review of text records within the Veterans Administration database are utilized to identify AEs related to the placement of central venous catheters (CVCs): a Natural Language Processing program and a phrase-matching algorithm. A sample of manually reviewed records were then compared to the results of both methods to assess sensitivity and specificity. The phrase-matching algorithm was found to be a sensitive but relatively non-specific method, whereas a natural language processing system was significantly more specific but less sensitive. Positive predictive values for each method estimated the CVC-associated AE rate at this institution to be 6.4 and 6.2%, respectively. Using both methods together results in acceptable sensitivity and specificity (72.0 and 80.1%, respectively). All methods including manual chart review are limited by incomplete or inaccurate clinician documentation. A secondary finding was related to the completeness of administrative data (ICD-9 and CPT codes) used to identify intensive care unit patients in whom a CVC was placed. Administrative data identified less than 11% of patients who had a CVC placed. This suggests that other methods, including automated methods such as phrase matching, may be more sensitive than administrative data in identifying patients with devices. Considerable potential exists for the use of such methods for the identification of patients at risk, AE surveillance, and prevention of AEs through decision support technologies. PMID:16901760

  17. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  18. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  19. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  20. Adverse outcome pathway and risks of anticoagulant rodenticides to predatory wildlife

    USGS Publications Warehouse

    Rattner, Barnett A.; Lazarus, Rebecca; Elliott, John E.; Shore, Richard F.; van den Brink, Nico

    2014-01-01

    Despite a long history of successful use, routine application of some anticoagulant rodenticides (ARs) may be at a crossroad due to new regulatory guidelines intended to mitigate risk. An adverse outcome pathway for ARs was developed to identify information gaps and end points to assess the effectiveness of regulations. This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. Risk assessments have led to restrictions affecting use of some second-generation ARs (SGARs) in North America. While the European regulatory community highlighted significant or unacceptable risk of ARs to nontarget wildlife, use of SGARs in most EU member states remains authorized due to public health concerns and the absence of safe alternatives. For purposes of conservation and restoration of island habitats, SGARs remain a mainstay for eradication of invasive species. There are significant data gaps related to exposure pathways, comparative species sensitivity, consequences of sublethal effects, potential hazards of greater AR residues in genetically resistant prey, effects of low-level exposure to multiple rodenticides, and quantitative data on the magnitude of nontarget wildlife mortality.

  1. Glaucoma eye drops adverse skin reactions.

    PubMed

    Cantisani, Carmen; Ambrifi, Marina; Frascani, Federica; Fazia, Gilda; Paolino, Giovanni; Lisi, Roberto; Calvieri, Stefano

    2014-01-01

    The term "Glaucoma" is used to describe a number of diseases of the eye characterized by a particular form of optic nerve damage that is often associated with high intraocular pressure (IOP). The open-angle glaucoma is the most common form that is also referred to as chronic glaucoma. This is described as an optic neuropathy with multifactorial nature in which there is a loss of characteristics of the optic nerve fibers. Therapeutic options for the treatment of this disease are different, you can take advantage of eye drops, laser therapy and conventional surgery or more combined treatments. Medicated eye drops are the most common way to treat glaucoma. Although eye drops are widely used, adverse reactions are not frequently observed and described. In particular, the adverse skin reactions are not frequently described in the literature, but often seen in dermatologic clinic, we reported their skin reactions and possible alternative treatments described in literature and their patent applications. PMID:25487259

  2. Adverse reactions to injectable soft tissue fillers.

    PubMed

    Requena, Luis; Requena, Celia; Christensen, Lise; Zimmermann, Ute S; Kutzner, Heinz; Cerroni, Lorenzo

    2011-01-01

    In recent years, injections with filler agents are often used for wrinkle-treatment and soft tissue augmentation by dermatologists and plastic surgeons. Unfortunately, the ideal filler has not yet been discovered and all of them may induce adverse reactions. Quickly biodegradable or resorbable agents may induce severe complications, but they will normally disappear spontaneously in a few months. Slowly biodegradable or nonresorbable fillers may give rise to severe reactions that show little or no tendency to spontaneous improvement. They may appear several years after the injection, when the patient does not remember which product was injected, and treatment is often insufficient. In this review, we discuss the most commonly used fillers, their most frequent adverse reactions as well as the characteristic histopathologic findings that allow the identification of the injected filler agent. In conclusion, histopathologic study remains as the gold standard technique to identify the responsible filler.

  3. Adverse events occurring after smallpox vaccination.

    PubMed

    Lane, J Michael; Goldstein, Joel

    2003-07-01

    We reviewed the literature on adverse events reported to occur after smallpox vaccination. Nearly one-half of the United States population is vaccinia-naïve and may be at risk for development of serious adverse events. We describe the clinical features of postvaccinial central nervous system disease, progressive vaccinia, eczema vaccinatum, accidental implantations, "generalized vaccinia," and the common erythematous and/or urticarial rashes. In the 1960s, death occurred approximately once in every million primary vaccinations, with fatalities resulting from progressive vaccinia, postvaccinial encephalitis, and eczema vaccinatum. Death in revaccinees occurred less commonly and almost entirely from progressive vaccinia. In today's population, death rates might be higher because of the increased prevalence of immune deficiency and atopic dermatitis.

  4. An Ss Model with Adverse Selection.

    ERIC Educational Resources Information Center

    House, Christopher L.; Leahy, John V.

    2004-01-01

    We present a model of the market for a used durable in which agents face fixed costs of adjustment, the magnitude of which depends on the degree of adverse selection in the secondary market. We find that, unlike typical models, the sS bands in our model contract as the variance of the shock increases. We also analyze a dynamic version of the model…

  5. Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

    PubMed

    Kerlin, Roy; Bolon, Brad; Burkhardt, John; Francke, Sabine; Greaves, Peter; Meador, Vince; Popp, James

    2016-02-01

    Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and

  6. Major adverse cardiac events during endurance sports.

    PubMed

    Belonje, Anne; Nangrahary, Mary; de Swart, Hans; Umans, Victor

    2007-03-15

    Major adverse cardiac events in endurance exercise are usually due to underlying and unsuspected heart disease. The investigators present an analysis of major adverse cardiac events that occurred during 2 consecutive annual long distance races (a 36-km beach cycling race and a 21-km half marathon) over the past 5 years. All patients with events were transported to the hospital. Most of the 62,862 participants were men (77%; mean age 40 years). Of these, 4 men (3 runners, 1 cyclist; mean age 48 years) collapsed during (n = 2) or shortly after the races, rendering a prevalence of 0.006%. Two patients collapsed after developing chest pain, 1 of whom needed resuscitation at the event site, which was successful. These patients had acute myocardial infarctions and underwent primary angioplasty. The third patient was resuscitated at the site but did not have coronary disease or inducible ventricular tachycardia or ventricular fibrillation and collapsed presumably because of catecholamine-induced ventricular fibrillation. The fourth patient experienced heat stroke and had elevated creatine kinase-MB and troponins in the absence of electrocardiographic changes. In conclusion, the risk for major adverse cardiac events during endurance sports in well-trained athletes is very low.

  7. Hierarchically nanotextured surfaces maintaining superhydrophobicity under severely adverse conditions

    NASA Astrophysics Data System (ADS)

    Maitra, Tanmoy; Antonini, Carlo; Auf der Mauer, Matthias; Stamatopoulos, Christos; Tiwari, Manish K.; Poulikakos, Dimos

    2014-07-01

    Superhydrophobic surfaces are highly desirable for a broad range of technologies and products affecting everyday life. Despite significant progress in recent years in understanding the principles of hydrophobicity, mostly inspired by surface designs found in nature, many man-made surfaces employ readily processable materials, ideal to demonstrate principles, but with little chance of survivability outside a very limited range of well-controlled environments. Here we focus on the rational development of robust, hierarchically nanostructured, environmentally friendly, metal-based (aluminum) superhydrophobic surfaces, which maintain their performance under severely adverse conditions. Based on their functionality, we superpose selected hydrophobic layers (i.e. self-assembled monolayers, thin films, or nanofibrous coatings) on hierarchically textured aluminum surfaces, collectively imparting high level robustness of superhydrophobicity under adverse conditions. These surfaces simultaneously exhibit chemical stability, mechanical durability and droplet impalement resistance. They impressively maintained their superhydrophobicity after exposure to severely adverse chemical environments like strong alkaline (pH ~ 9-10), acidic (pH ~ 2-3), and ionic solutions (3.5 weight% of sodium chloride), and could simultaneously resist water droplet impalement up to an impact velocity of 3.2 m s-1 as well as withstand standard mechanical durability tests.Superhydrophobic surfaces are highly desirable for a broad range of technologies and products affecting everyday life. Despite significant progress in recent years in understanding the principles of hydrophobicity, mostly inspired by surface designs found in nature, many man-made surfaces employ readily processable materials, ideal to demonstrate principles, but with little chance of survivability outside a very limited range of well-controlled environments. Here we focus on the rational development of robust, hierarchically

  8. Neural systems supporting cognitive-affective interactions in adolescence: the role of puberty and implications for affective disorders

    PubMed Central

    Ladouceur, Cecile D.

    2012-01-01

    Evidence from longitudinal studies suggests that adolescence may represent a period of vulnerability that, in the context of adverse events, could contribute to developmental trajectories toward behavioral and emotional health problems, including affective disorders. Adolescence is also a sensitive period for the development of neural systems supporting cognitive-affective processes, which have been implicated in the pathophysiology of affective disorders such as anxiety and mood disorders. In particular, the onset of puberty brings about a cascade of physical, hormonal, psychological, and social changes that contribute in complex ways to the development of these systems. This article provides a brief overview of neuroimaging research pertaining to the development of cognitive-affective processes in adolescence. It also includes a brief review of evidence from animal and human neuroimaging studies suggesting that sex steroids influence the connectivity between prefrontal cortical and subcortical limbic regions in ways that contribute to increased reactivity to emotionally salient stimuli. We integrate these findings in the context of a developmental affective neuroscience framework suggesting that the impact of rising levels of sex steroids during puberty on fronto-limbic connectivity may be even greater in the context of protracted development of prefrontal cortical regions in adolescence. We conclude by discussing the implications of these findings for future research aimed at identifying neurodevelopmental markers of risk for future onset of affective disorders. PMID:22969712

  9. [Contrast sensitivity in glaucoma].

    PubMed

    Bartos, D

    1989-05-01

    Author reports on results of the contrast sensitivity examinations using the Cambridge low-contrast lattice test supplied by Clement Clarke International LTD, in patients with open-angle glaucoma and ocular hypertension. In glaucoma patients there was observed statistically significant decrease of the contrast sensitivity. In patients with ocular hypertension decrease of the contrast sensitivity was in patients affected by corresponding changes of the visual field and of the optical disc. The main advantages of the Cambridge low-contrast lattice test were simplicity, rapidity and precision of its performance. PMID:2743444

  10. Adverse effects of bisphenol A on male reproductive function.

    PubMed

    Manfo, Faustin Pascal Tsagué; Jubendradass, Rajamanickam; Nantia, Edouard Akono; Moundipa, Paul Fewou; Mathur, Premendu Prakash

    2014-01-01

    BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the

  11. AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats.

    PubMed

    Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

    2009-12-01

    The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than 30 brain regions. The measurements were performed using alpha-[(14)C]methyl-l-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental setup) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be

  12. AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats

    PubMed Central

    Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

    2009-01-01

    The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than thirty brain regions. The measurements were performed using α-[14C]methyl-L-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental set up) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be

  13. Performance Characteristics of a Methodology to Quantify Adverse Events over Time in Hospitalized Patients

    PubMed Central

    Sharek, Paul J; Parry, Gareth; Goldmann, Donald; Bones, Kate; Hackbarth, Andrew; Resar, Roger; Griffin, Frances A; Rhoda, Dale; Murphy, Cathy; Landrigan, Christopher P

    2011-01-01

    Objective To assess the performance characteristics of the Institute for Healthcare Improvement Global Trigger Tool (GTT) to determine its reliability for tracking local and national adverse event rates. Data Sources Primary data from 2008 chart reviews. Study Design A retrospective study in a stratified random sample of 10 North Carolina hospitals. Hospital-based (internal) and contract research organization–hired (external) reviewers used the GTT to identify adverse events in the same 10 randomly selected medical records per hospital in each quarter from January 2002 through December 2007. Data Collection/Extraction Interrater and intrarater reliability was assessed using κ statistics on 10 percent and 5 percent, respectively, of selected medical records. Additionally, experienced GTT users reviewed 10 percent of records to calculate internal and external teams' sensitivity and specificity. Principal Findings Eighty-eight to 98 percent of the targeted 2,400 medical records were reviewed. The reliability of the GTT to detect the presence, number, and severity of adverse events varied from κ=0.40 to 0.60. When compared with a team of experienced reviewers, the internal teams' sensitivity (49 percent) and specificity (94 percent) exceeded the external teams' (34 and 93 percent), as did their performance on all other metrics. Conclusions The high specificity, moderate sensitivity, and favorable interrater and intrarater reliability of the GTT make it appropriate for tracking local and national adverse event rates. The strong performance of hospital-based reviewers supports their use in future studies. PMID:20722749

  14. Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study.

    PubMed

    Rifkin-Graboi, A; Kong, L; Sim, L W; Sanmugam, S; Broekman, B F P; Chen, H; Wong, E; Kwek, K; Saw, S-M; Chong, Y-S; Gluckman, P D; Fortier, M V; Pederson, D; Meaney, M J; Qiu, A

    2015-10-27

    Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother-infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning.

  15. Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study

    PubMed Central

    Rifkin-Graboi, A; Kong, L; Sim, L W; Sanmugam, S; Broekman, B F P; Chen, H; Wong, E; Kwek, K; Saw, S-M; Chong, Y-S; Gluckman, P D; Fortier, M V; Pederson, D; Meaney, M J; Qiu, A

    2015-01-01

    Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother–infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning. PMID:26506054

  16. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  17. Are PRO discharge screens associated with postdischarge adverse outcomes?

    PubMed Central

    Wei, F.; Mark, D.; Hartz, A.; Campbell, C.

    1995-01-01

    OBJECTIVE. We evaluate whether patient outcomes may be affected by possible errors in care at discharge as assessed by Peer Review Organizations (PROs). DATA SOURCES/STUDY SETTING. The three data sources for the study were (1) the generic screen results of a 3 percent random sample of Medicare beneficiaries age 65 years or older who were admitted to California hospitals between 1 July 1987 and 30 June 1988 (n = 20,136 patients); (2) the 1987 and 1988 California Medicare Provided Analysis and Review (MEDPAR) data files; and (3) the American Hospital Association (AHA) 1988 Annual Survey of Hospitals. STUDY DESIGN. Multivariate logistic regression analysis was used to evaluate the association between the results of generic discharge administered by the PROs and two patient outcomes: mortality and readmission within 30 days. The analysis was adjusted for other patient characteristics recorded on the uniform discharge abstract. PRINCIPAL FINDINGS. Four discharge screens indicated an increased risk of an adverse outcome-absence of documentation of discharge planning, elevated temperature, abnormal pulse, and unaddressed abnormal test results at discharge. The other three discharge screens examined-abnormal blood pressure, IV fluids or drugs, and wound drainage before discharge-were unrelated to postdischarge adverse outcomes. CONCLUSIONS. Generic discharge screens based on inadequate discharge planning, abnormal pulse, increased temperature, or unaddressed abnormal tests may be important indicators of substandard care. Other discharge screens apparently do not detect errors in care associated with major consequences for patients. PMID:7649753

  18. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

  19. Adverse food reactions--an emerging issue for adults.

    PubMed

    Skypala, Isabel

    2011-12-01

    Adverse reactions to foods are classified according to the presence or absence of involvement of the immune system, which may or may not include the production of immunoglobulin E (IgE) antibodies. This review focuses on the epidemiology, diagnosis, and management of adverse food reactions, primarily in adults, and excluding celiac disease and lactose intolerance. Reported reactions to foods are often believed to be manifestations of a food allergy; however, IgE-mediated food allergy only affects 1% to 4% of adults, with seafood, tree nuts, peanuts, fruits, and vegetables being the most common triggers. Diagnosis is challenging and most commonly achieved through careful evaluation of clinical history followed by elimination and reintroduction or challenge with the suspected offending food. With acute-onset allergic reactions, estimation of food-specific IgE antibodies is frequently used to confirm or refute the diagnosis. Recent developments, such as single allergen assays, enhance the diagnosis of IgE-mediated food allergy, but the gold standard remains oral food challenge. Despite recent advances in the management of food allergy, including the promotion of oral tolerance, the mainstay of management is still the avoidance of food triggers. Dietary management can be compromised by nutritional inadequacy, accidental exposure, food labeling, and quality of life or adherence issues. It is essential that adults with confirmed food allergy receive optimal nutrition and dietetic support to enable them to manage their condition. PMID:22117664

  20. Adverse neurological outcomes in Nigerian children with sickle cell disease.

    PubMed

    Lagunju, I A; Brown, B J

    2012-12-01

    Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria. PMID:23129067

  1. Integrated decision strategies for skin sensitization hazard.

    PubMed

    Strickland, Judy; Zang, Qingda; Kleinstreuer, Nicole; Paris, Michael; Lehmann, David M; Choksi, Neepa; Matheson, Joanna; Jacobs, Abigail; Lowit, Anna; Allen, David; Casey, Warren

    2016-09-01

    One of the top priorities of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by the Organisation for Economic Co-operation and Development (OECD). Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens assay. Data for six physicochemical properties, which may affect skin penetration, were also collected, and skin sensitization read-across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty-four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89-96% for the test set and 96-99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non-animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA. PMID:26851134

  2. Progression pattern and adverse events with bevacizumab in glioblastoma

    PubMed Central

    Mamo, A.; Baig, A.; Azam, M.; Rho, Y.S.; Sahebjam, S.; Muanza, T.; Owen, S.; Petrecca, K.; Guiot, M.C.; Al-Shami, J.; Sharma, R.; Kavan, P.

    2016-01-01

    Background The use of bevacizumab in the management of glioblastoma multiforme (gbm) remains controversial. In Canada, bevacizumab is approved for the treatment of recurrent gbm. We describe a pattern of progression across treatment lines in gbm. Methods During 2008–2014, 64 patients diagnosed with gbm were treated with bevacizumab at McGill University hospitals. Of those patients, 30 (46.9%) received bevacizumab in the first line (B1L), and 34 (53.1%) received it in the second line and beyond (B2L+). The average length of treatment with bevacizumab was 24.4 weeks (range: 0–232.7 weeks). The patterns of progression were categorized as local, distant, diffuse, multifocal, or multi-pattern. Results Local progression was seen in 46.7% of B1L patients and 26.5% of B2L+ patients, distant in 3.3% and 2.9%, diffuse in 20% and 47%, multifocal in 10% and 8.8%, and multi-pattern in 3.3% and 11.8%. No differences between the groups were observed for the distant (p = 0.3) or diffuse (p = 0.4) patterns. Grades 3 and 4 adverse events in the B1L and B2L+ groups were fatigue (33.3% vs. 17.6% respectively), hypertension (26.7% vs. 5.9%), thrombocytopenia (26.7% vs. 11.8%), neutropenia (26.7% vs. 11.8%), anemia (23.3% vs. 11.8%), leucopenia (20% vs. 8.8%), deep vein thrombosis (23.3% vs. 5.9%), seizure (16.7% vs. 8.8%), brain hemorrhage (6.7% vs. <1%), and delayed wound healing (6.7% vs. 2.9%). More total grades 3 and 4 adverse events occurred in the B1L group (p = 0.000519). Conclusions In our cohort, patterns of progression were not different in B1L and B2L+ patients. Moreover, both groups experienced similar adverse events, although more grades 3 and 4 events occurred in the B1L group, implying that severe adverse events in B1L patients could negatively affect survival outcomes.

  3. Anticoagulation-associated adverse drug events

    PubMed Central

    Piazza, Gregory; Nguyen, Thanh Nha; Cios, Deborah; Labreche, Matthew; Hohlfelder, Benjamin; Fanikos, John; Fiumara, Karen; Goldhaber, Samuel Z.

    2011-01-01

    Purpose Anticoagulant drugs are among the most common medications that cause adverse drug events (ADEs) in hospitalized patients. We performed a five-year retrospective study at Brigham and Women’s Hospital to determine clinical characteristics, types, root causes, and outcomes of anticoagulant-associated adverse drug events (ADEs). Methods We reviewed all inpatient anticoagulant-associated ADEs, including adverse drug reactions (ADRs) and medication errors, reported at Brigham and Women’s Hospital through the Safety Reporting System from May 2004 to May 2009. We also collected data regarding the cost associated with hospitalizations in which ADRs occurred. Results Of 463 anticoagulant-associated ADEs, 226 were MEs (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR. Seventy percent of anticoagulant-associated ADEs were potentially preventable. Transcription errors (48%) were the most frequent root cause of anticoagulant-associated medication errors, while medication errors (40%) were a common root cause of anticoagulant-associated ADRs. Death within 30 days of anticoagulant-associated ADEs occurred in 11% of patients. After an anticoagulant-associated ADR, most hospitalization expenditures were attributable to nursing costs (mean $33,189 per ADR) followed by pharmacy costs (mean $7,451 per ADR). Conclusion Most anticoagulant-associated ADEs among inpatients result from medication errors and are therefore potentially preventable. We observed an elevated 30-day mortality rate among patients who suffered an anticoagulant-associated ADE and high hospitalization costs following ADRs. Further Quality Improvement efforts to reduce anticoagulant-associated medication errors are warranted to improve patient safety and decrease health care expenditures. PMID:22114827

  4. Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system.

    PubMed

    Bixler, E O; Kales, A; Brubaker, B H; Kales, J D

    1987-01-01

    The rates of reported adverse drug reactions involving the central nervous system were compared among patients taking any of three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam. These rates, based upon data collected through the spontaneous reporting system of the Food and Drug Administration, were controlled for the number and size of new prescriptions for each drug. In general, triazolam had much higher overall rates than did the other two drugs. Hyperexcitability and withdrawal effects were greatest for triazolam and least for flurazepam. Amnesia was reported almost exclusively with triazolam. Rates for other cognitive as well as affective and other behavioral effects were also much greater for triazolam and about equal for the other two drugs. Finally, daytime sedation was reported slightly more for flurazepam than triazolam and least for temazepam which was also reported most frequently as lacking hypnotic effect. PMID:2892212

  5. Reducing medical errors and adverse events.

    PubMed

    Pham, Julius Cuong; Aswani, Monica S; Rosen, Michael; Lee, HeeWon; Huddle, Matthew; Weeks, Kristina; Pronovost, Peter J

    2012-01-01

    Medical errors account for ∼98,000 deaths per year in the United States. They increase disability and costs and decrease confidence in the health care system. We review several important types of medical errors and adverse events. We discuss medication errors, healthcare-acquired infections, falls, handoff errors, diagnostic errors, and surgical errors. We describe the impact of these errors, review causes and contributing factors, and provide an overview of strategies to reduce these events. We also discuss teamwork/safety culture, an important aspect in reducing medical errors.

  6. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  7. Adverse effects of equine rabies immune gobulin.

    PubMed

    Wilde, H; Chomchey, P; Prakongsri, S; Puyaratabandhu, P; Chutivongse, S

    1989-02-01

    Following a recently published prospective study of 485 recipients of equine rabies immune globulin (ERIG) manufactured by Pasteur Vaccins (Paris), this paper reports a study of 323 postexposure rabies patients receiving ERIG manufactured by the Swiss Vaccine and Serum Institute (Berna). It is concluded that there may be significant differences in adverse reaction rates, reflecting differing manufacturing or purification processes and protein content. Further studies of different ERIG products and of different lots of the same product are needed while ERIG remains an essential component of postexposure rabies treatment in developing countries.

  8. Agomelatine: a review of adverse effects.

    PubMed

    2013-03-01

    More pharmacovigilance data on agomelatine became available in 2012. The main sources of information were surveillance data from the French national monitoring system, EU periodic safety update reports (PSURs), and the European pharmacovigilance database. The principal adverse effects of agomelatine consist of hepatic, pancreatic, neuropsychiatric, muscular and cutaneous disorders. The harms associated with agomelatine, which has no proven efficacy in depression, clearly outweigh the benefits. Until regulatory agencies decide to withdraw agomelatine from the market, it is up to healthcare professionals to protect patients from this unnecessarily dangerous drug.

  9. Sensitive skin.

    PubMed

    Misery, L; Loser, K; Ständer, S

    2016-02-01

    Sensitive skin is a clinical condition defined by the self-reported facial presence of different sensory perceptions, including tightness, stinging, burning, tingling, pain and pruritus. Sensitive skin may occur in individuals with normal skin, with skin barrier disturbance, or as a part of the symptoms associated with facial dermatoses such as rosacea, atopic dermatitis and psoriasis. Although experimental studies are still pending, the symptoms of sensitive skin suggest the involvement of cutaneous nerve fibres and neuronal, as well as epidermal, thermochannels. Many individuals with sensitive skin report worsening symptoms due to environmental factors. It is thought that this might be attributed to the thermochannel TRPV1, as it typically responds to exogenous, endogenous, physical and chemical stimuli. Barrier disruptions and immune mechanisms may also be involved. This review summarizes current knowledge on the epidemiology, potential mechanisms, clinics and therapy of sensitive skin. PMID:26805416

  10. Adverse Effects of Psychotropic Medications: A Call to Action.

    PubMed

    Mago, Rajnish

    2016-09-01

    Adverse effects are common, bothersome, and a leading cause of discontinuation of treatment. The methodology for evaluating adverse effects of medications has been greatly neglected, however, especially in comparison to the methodology for assessment of efficacy of medications. Existing methods for assessment and reporting of adverse effects have important limitations leading to lack of much-needed data related to adverse effects. Lastly, there is little systematic research into management of most adverse effects. A series of recommendations are made in this article about how to improve identification, assessment, reporting, and management of adverse effects. PMID:27514294

  11. Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

    PubMed Central

    Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

    2016-01-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  12. Familial risk and childhood adversity interplay in the onset of psychosis

    PubMed Central

    Trotta, Antonella; Di Forti, Marta; Iyegbe, Conrad; Green, Priscilla; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Murray, Robin M.

    2015-01-01

    Background The association between childhood adversity and psychosis in adulthood is well established. However, genetic factors might confound or moderate this association. Aims Using a catchment-based case–control sample, we explored the main effects of, and interplay between, childhood adversity and family psychiatric history on the onset of psychosis. Method Childhood adversity (parental separation and death, physical and sexual abuse) was assessed retrospectively in 224 individuals with a first presentation of psychosis and 256 community controls from South London, UK. Occurrence of psychotic and affective disorders in first-degree relatives was ascertained with the Family Interview for Genetic Studies (FIGS). Results Parental history of psychosis did not confound the association between childhood adversity and psychotic disorder. There was no evidence that childhood adversity and familial liability combined synergistically to increase odds of psychosis beyond the effect of each individually. Conclusions Our results do not support the hypothesis that family psychiatric history amplifies the effect of childhood adversity on odds of psychosis. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence. PMID:27703716

  13. Adversity in preschool-aged children: Effects on salivary interleukin-1β.

    PubMed

    Tyrka, Audrey R; Parade, Stephanie H; Valentine, Thomas R; Eslinger, Nicole M; Seifer, Ronald

    2015-05-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary interleukin (IL)-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records. Contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. The number of past-month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Postchallenge IL-1β displayed positive associations with each adversity variable, but these were not significant. CRP was not significantly associated with any of the adversity variables. Given the evidence suggesting the involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  14. Adverse effects of outdoor pollution in the elderly

    PubMed Central

    Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  15. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  16. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  17. Early adversity, immunity and infectious disease.

    PubMed

    Avitsur, Ronit; Levy, Sigal; Goren, Naama; Grinshpahet, Rachel

    2015-01-01

    Complex interactions between biological, behavioral and environmental factors are involved in mediating individual differences in health and disease. In this review, we present evidence suggesting that increased vulnerability to infectious disease may be at least, in part, due to long-lasting effects of early life psychosocial adversities. Studies have shown that maternal psychosocial stress during pregnancy is associated with long lasting changes in immune function and disease resistance in the offspring. Studies further indicated that harsh environmental conditions during the neonatal period may also cause lasting changes in host response to infectious disease. Although the mechanisms involved in these effects have not been fully examined, several potential mediators have been described, including changes in the development of the offspring hypothalamic-pituitary-adrenal axis, alterations in epigenetic pathways, stress-related maternal health risk behavior and infection during pregnancy. Although there are ample literature indicating that perinatal psychosocial stress increases vulnerability to disease, other reports suggest that mild predictable stressors may benefit the organism and allow better coping with future stressors. Thus, understanding the possible consequences of perinatal adversities and the mechanisms that are involved in immune regulation is important for increasing awareness to the potential outcomes of early negative life events and providing insight into potential therapies to combat infection in vulnerable individuals.

  18. Adverse reactions to food: allergies and intolerances.

    PubMed

    Montalto, Massimo; Santoro, Luca; D'Onofrio, Ferruccio; Curigliano, Valentina; Gallo, Antonella; Visca, Dina; Cammarota, Giovanni; Gasbarrini, Antonio; Gasbarrini, Giovanni

    2008-01-01

    All the anomalous reactions secondary to food ingestion are defined as 'adverse reactions to food'. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reactions can be divided into 'food allergies' when they recognize immunological mechanisms, and 'food intolerances' when there are no immunological implications. The diagnostic approach to adverse reactions to food is based on accurate clinical history and objective examination, and further execution of specific tests when allergy or intolerance is suspected. The therapy for food allergies is the elimination of the food to which hypersensibility has been found; this strategy can lead, especially in pediatric age, to tolerance. If elimination diets cannot be completely performed, or if it is not possible to identify the food to eliminate, some drugs (e.g. antihistaminics, steroids, etc.) can be administered. Specific allergen immunotherapy has been recently introduced. Fundamental is food allergy prevention, especially in high-risk subjects. The therapeutic approach to secondary food intolerances is based principally on primitive disease resolution; on the other hand, some specific treatments (e.g. beta-galactosidases in lactose malabsorption) are available in case of primary intolerance. PMID:18431058

  19. Ranking Adverse Drug Reactions With Crowdsourcing

    PubMed Central

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel

    2015-01-01

    Background There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective The intent of the study was to rank ADRs according to severity. Methods We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making. PMID:25800813

  20. Adverse outcome pathway development II: best practices.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  1. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  2. Adverse outcome pathway development II: best practices.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach.

  3. Adverse Outcome Pathway Development II: Best Practices

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  4. [Adverse drug reactions in pregnant women].

    PubMed

    Lacroix, Isabelle; Cabou, Cendrine; Montastruc, Jean-Louis; Damase-Michel, Christine

    2007-01-01

    A Prospective pharmacovigilance survey of adverse drug reactions (ADRs) in pregnant women was performed in collaboration with gynaecologists and obstetricians of Midi-Pyrenees area (south west of france). The aim of the study was to evaluate the incidence of adverse drug reactions in pregnant women. The incidence of ADRs in pregnant women was low: 0.3%. Moreover, a retrospective pharmacoepidemiological study was conducted to characterize ADRs in pregnant women. Reports of ADRs collected in the Midi-Pyrenees pharmacovigilance centre from 1982 to 2002 were used: type of ADRs, drugs involved and potential risk factors were compared for pregnant women and for age-matched non pregnant women. Forty seven and 94 reports of ADRs were collected in pregnant and non-pregnant women respectively. Anaphylactic reactions were only observed in pregnant women (3 cases, p = 0.04). We observed 1 ADR related stillbirth (due to anaphylactic reaction) in pregnant women. Drugs for gynaecological and cardiovascular systems were more frequently involved in ADRs in pregnant women than in controls. ADRs mainly occurred during the third trimester of pregnancy. The incidence of ADRs is very low in pregnant women. However, one must pay attention on the risk of anaphylactic reactions in pregnant women. PMID:18206108

  5. Adverse reactions to antituberculosis drugs in Manguinhos, Rio de Janeiro, Brazil

    PubMed Central

    Damasceno, Glauciene Santana; Guaraldo, Lusiele; Engstrom, Elyne Montenegro; Filha, Mariza Miranda Theme; Santos, Reinaldo Souza-; Vasconcelos, Ana Gloria Godoi; Rozenfeld, Suely

    2013-01-01

    OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%), the skin and appendages (21.4%), and the central and peripheral nervous systems (14.3%). Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. “Probable reactions” (75%) predominated over “possible reactions” (24%). In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6%) of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I). A high dropout rate from tuberculosis treatment (24.4%) was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs. PMID:23644852

  6. Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study, Peru

    PubMed Central

    Wingfield, Tom; Boccia, Delia; Tovar, Marco; Gavino, Arquímedes; Zevallos, Karine; Montoya, Rosario; Lönnroth, Knut; Evans, Carlton A.

    2014-01-01

    Background Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs. Methods and Findings From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1

  7. Race, Gender, and Chains of Disadvantage: Childhood Adversity, Social Relationships, and Health

    PubMed Central

    Umberson, Debra; Williams, Kristi; Thomas, Patricia A.; Liu, Hui; Thomeer, Mieke Beth

    2014-01-01

    We use a life course approach to guide an investigation of relationships and health at the nexus of race and gender. We consider childhood as a sensitive period in the life course, during which significant adversity may launch chains of disadvantage in relationships throughout the life course that then have cumulative effects on health over time. Data from a nationally representative panel study (Americans’ Changing Lives, N=3,477) reveal substantial disparities between black and white adults, especially pronounced among men, in the quality of close relationships and in the consequences of these relationships for health. Greater childhood adversity helps to explain why black men have worse health than white men, and some of this effect appears to operate through childhood adversity’s enduring influence on relationship strain in adulthood. Stress that occurs in adulthood plays a greater role than childhood adversity in explaining racial disparities in health among women. PMID:24578394

  8. Potential adverse effects of omega-3 Fatty acids in dogs and cats.

    PubMed

    Lenox, C E; Bauer, J E

    2013-01-01

    Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions.

  9. Climate Sensitivity

    SciTech Connect

    Lindzen, Richard

    2011-11-09

    Warming observed thus far is entirely consistent with low climate sensitivity. However, the result is ambiguous because the sources of climate change are numerous and poorly specified. Model predictions of substantial warming aredependent on positive feedbacks associated with upper level water vapor and clouds, but models are notably inadequate in dealing with clouds and the impacts of clouds and water vapor are intimately intertwined. Various approaches to measuring sensitivity based on the physics of the feedbacks will be described. The results thus far point to negative feedbacks. Problems with these approaches as well as problems with the concept of climate sensitivity will be described.

  10. Adverse allergic reaction to Technetium-99m methylene diphosphonate

    SciTech Connect

    Spicer, J.A.; Preston, D.F.; Stephens, R.L.

    1985-04-01

    Adverse allergic reactions to radiopharmaceuticals are rare but have been documented in the literature. This report presents data consistent with a definite adverse reaction to the radiopharmaceutical (/sup 99m/Tc)MDP.

  11. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  12. Adverse Outcome Pathways – Tailoring Development to Support Use

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

  13. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  14. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease

    PubMed Central

    Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36–2.62), maltreatment (1.81; 1.38–2.38), or social isolation (1.87; 1.38–2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The

  15. Monoamine oxidase A and childhood adversity as risk factors for conduct disorder in females

    PubMed Central

    Prom-Wormley, E. C.; Eaves, L. J.; Foley, D. L.; Gardner, C. O.; Archer, K. J.; Wormley, B. K.; Maes, H. H.; Riley, B. P.; Silberg, J. L.

    2014-01-01

    Background Recent studies among males have reported a genotype-environment interaction (G × E) in which low-activity alleles at the monoamine oxidase A (MAOA) locus conferred greater sensitivity to the effects of childhood adversity on risk for conduct disorder (CD). So far, few studies of females have controlled for gene-environment correlation or used females heterozygous for this X-linked gene. Method Logistic regression analysis of a sample of 721 females ages 8-17 years from the longitudinal Virginia Twin Study of Adolescent Behavioral Development (VTSABD) assessed the additive effects of MAOA genotypes on risk for CD, together with the main effect of childhood adversity and parental antisocial personality disorder (ASP), as well as the interaction of MAOA with childhood adversity on risk for CD. Results A significant main effect of genotype on risk for CD was detected, where low-activity MAOA imparted the greatest risk to CD in girls while controlling for the significant effects of maternal ASP and childhood adversity. Significant G × E with weak effect was detected when environmental exposure was untransformed, indicating a higher sensitivity to childhood adversity in the presence of the high-activity MAOA allele. The interaction was no longer statistically significant after applying a ridit transformation to reflect the sample sizes exposed at each level of childhood adversity. Conclusions The main effect of MAOA on risk for CD in females, its absence in males and directional difference of interaction is suggestive of genotype-sex interaction. As the effect of G × E on risk for CD was weak, its inclusion is not justified. PMID:18752729

  16. Gluten Sensitivity

    MedlinePlus

    Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different ...

  17. Climate Sensitivity

    NASA Astrophysics Data System (ADS)

    Hansen, J.

    2007-12-01

    Discussion of climate sensitivity requires careful definition of forcings, feedbacks and response times, indeed, foggy definitions have produced flawed assessments of climate sensitivity. The best information available on climate sensitivity comes from insightful interpretation of the Earth's history aided by quantitative information from climate models and understanding of climate processes. Climate sensitivity is a strong function of time scale, in part because of the nature of climate feedbacks. Unfortunately for humanity, the preponderance of feedbacks on the century time scale appears to be positive. The chief implication is the need for a sharp reversal in the trend of human-made climate forcing, if we are to avoid creating a planet that is dramatically different than the one on which civilization developed.

  18. Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events

    PubMed Central

    Roitmann, Eva; Eriksson, Robert; Brunak, Søren

    2014-01-01

    Purpose: New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse event co-occurrences. Methods: We analyzed the similarity of adverse event profiles of 2347 patients extracted from EMRs from a mental health center in Denmark. The patients were clustered based on their adverse event profiles and the similarities were presented as a network. The set of adverse events in each main patient cluster was evaluated. Co-occurrences of adverse events in patients (p-value < 0.01) were identified and presented as well. Results: We found that each cluster of patients typically had a most distinguishing adverse event. Examination of the co-occurrences of adverse events in patients led to the identification of potentially interesting adverse event correlations that may be further investigated as well as provide further patient stratification opportunities. Conclusions: We have demonstrated the feasibility of a novel approach in pharmacovigilance to stratify patients based on fine-grained adverse event profiles, which also makes it possible to identify adverse event correlations. Used on larger data sets, this data-driven method has the potential to reveal unknown patterns concerning adverse event occurrences. PMID:25249979

  19. Participation in a public insurance program: subsidies, crowd-out, and adverse selection.

    PubMed

    Long, Stephen H; Marquis, M Susan

    2002-01-01

    This paper examines how varying the level of subsidies affects participation in a public insurance program, crowd-out of private insurance, and adverse selection. We study the experience in Washington's Basic Health program in 1997. Findings show that adverse selection is not a problem in voluntary public programs. Increasing subsidies have only modest effects on participation in subsidized programs, though the gains are not at the expense of the private market. Overall participation in the subsidized plan is also modest, even though participants benefit from it. The challenge to policymakers is to find program design characteristics, beyond subsidies, that attract the uninsured.

  20. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function.

    PubMed

    Anacker, Christoph; O'Donnell, Kieran J; Meaney, Michael J

    2014-09-01

    We review studies with human and nonhuman species that examine the hypothesis that epigenetic mechanisms, particularly those affecting the expression of genes implicated in stress responses, mediate the association between early childhood adversity and later risk of depression. The resulting studies provide evidence consistent with the idea that social adversity, particularly that involving parent-offspring interactions, alters the epigenetic state and expression of a wide range of genes, the products of which regulate hypothalamic-pituitary-adrenal function. We also address the challenges for future studies, including that of the translation of epigenetic studies towards improvements in treatments.

  1. Sensitivity analysis of an Ocean Carbon Cycle Model in the North Atlantic: an investigation of parameters affecting the air-sea CO2 flux, primary production and export of detritus

    NASA Astrophysics Data System (ADS)

    Scott, V.; Kettle, H.; Merchant, C. J.

    2010-12-01

    The sensitivity of the biological parameters in a nutrient-phytoplankton-zooplankton-detritus (NPZD) model in the calculation of the air-sea CO2 flux, primary production and detrital export is analysed. The NPZD model is the Hadley Centre Ocean Carbon Cycle model (HadOCC) from the UK Met Office, used in the Hadley Centre Coupled Model 3 (HadCM3) and FAst Met Office and Universities Simulator (FAMOUS) GCMs. Here, HadOCC is coupled to the 1-D General Ocean Turbulence Model (GOTM) and forced with European Centre for Medium-Range Weather Forecasting meteorology to undertake a sensitivity analysis of its twenty biological parameters. Analyses are performed at three sites in the EuroSITES European Ocean Observatory Network: the Central Irminger Sea (60° N 40° W), the Porcupine Abyssal Plain (49° N 16° W) and the European Station for Time series in the Ocean Canary Islands (29° N 15° W) to assess variability in parameter sensitivities at different locations in the North Atlantic Ocean. Reasonable changes to the values of key parameters are shown to have a large effect on the calculation of the air-sea CO2 flux, primary production, and export of biological detritus to the deep ocean. Changes in the values of key parameters have a greater effect in more productive regions than in less productive areas. We perform the analysis using one-at-a-time perturbations and using a statistical emulator, and compare results. The most sensitive parameters are generic to many NPZD ocean ecosystem models. The air-sea CO2 flux is most influenced by variation in the parameters that control phytoplankton growth, detrital sinking and carbonate production by phytoplankton (the rain ratio). Primary production is most sensitive to the parameters that define the shape of the photosythesis-irradiance curve. Export production is most sensitive to the parameters that control the rate of detrital sinking and the remineralisation of detritus.

  2. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Adverse reaction file. 606.170 Section 606.170 Food... reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding... investigation of each reported adverse reaction shall be made. A written report of the investigation of...

  3. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. Link to an amendment published at 77 FR 18, Jan. 3, 2012. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood...

  4. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  5. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  6. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  7. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  8. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  9. Adversity and Resilience: A Synthesis of International Research

    ERIC Educational Resources Information Center

    Noltemeyer, Amity L.; Bush, Kevin R.

    2013-01-01

    Children and adolescents worldwide experience a variety of adversities that have the potential to disrupt typical development. However, some of these individuals exhibit resilience, evidencing normal development in the face of adversity. Here we review research on these constructs of risk, adversity, and resilience; synthesize international…

  10. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a)...

  11. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    PubMed

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity. PMID:26260665

  12. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    PubMed

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

  13. The vomeronasal organ and chemical sensitivity: a hypothesis.

    PubMed

    Greene, Glenn J; Kipen, Howard M

    2002-08-01

    Environmental exposures to very low levels of airborne chemicals are associated with adverse symptoms, often affecting multiple organ systems, in the phenomenon of chemical sensitivity (CS). Recent surveys suggest a significant prevalence of chemically sensitive subjects in the United States, but the mechanism linking exposure to symptoms remains unclear, despite the advancement of a variety of theoretical models. In many of these models, exposure of the nasal respiratory system to an airborne agent is the first step in the pathway leading to symptoms. In this article, we advance the hypothesis that interactions between environmental chemicals and the vomeronasal organ (VNO) may play a role in the etiology of CS. The VNO, a bilateral, tubular organ located in the nose, serves in animals as part of a sensitive chemosensory system; however, evidence suggesting that the VNO retains a functional role in the adult human is controversial. Reported characteristics of the human VNO relevant to CS, including location, prevalence, selective sensitivity to airborne chemical exposure, and capacity to produce systemic effects, are discussed within the context of this ongoing debate. Beyond relevance to CS, the demonstration of an active, adult VNO could have significant impact on environmental toxicology.

  14. The vomeronasal organ and chemical sensitivity: a hypothesis.

    PubMed Central

    Greene, Glenn J; Kipen, Howard M

    2002-01-01

    Environmental exposures to very low levels of airborne chemicals are associated with adverse symptoms, often affecting multiple organ systems, in the phenomenon of chemical sensitivity (CS). Recent surveys suggest a significant prevalence of chemically sensitive subjects in the United States, but the mechanism linking exposure to symptoms remains unclear, despite the advancement of a variety of theoretical models. In many of these models, exposure of the nasal respiratory system to an airborne agent is the first step in the pathway leading to symptoms. In this article, we advance the hypothesis that interactions between environmental chemicals and the vomeronasal organ (VNO) may play a role in the etiology of CS. The VNO, a bilateral, tubular organ located in the nose, serves in animals as part of a sensitive chemosensory system; however, evidence suggesting that the VNO retains a functional role in the adult human is controversial. Reported characteristics of the human VNO relevant to CS, including location, prevalence, selective sensitivity to airborne chemical exposure, and capacity to produce systemic effects, are discussed within the context of this ongoing debate. Beyond relevance to CS, the demonstration of an active, adult VNO could have significant impact on environmental toxicology. PMID:12194902

  15. Monitoring Adverse Drug Reactions: A Preliminary Study

    PubMed Central

    Reynolds, J. L.

    1981-01-01

    The feasibility of family physicians functioning as monitors of adverse drug reactions (ADR) was examined over one month in ten practices. This was done as a preliminary trial, before attempting to use the 200 family physicians of the National Reporting System of the College of Family Physicians of Canada to monitor ADRs on a national basis. Both of these trials were designed to examine the feasibility of family physicians acting as prospective monitors of ADRs in newly marketed drugs and to identify a drug group suitable for monitoring. This study examined the detection of ADRs, prescribing and practice profiles. No firm conclusion could be reached as to the value of family doctors monitoring ADRs. This study supports the evidence that older patients receive more drugs and are at even greater risk of an ADR. Antibiotics, cardiovascular, anti-inflammatory or antidepressant drugs are suggested as those most suitable for prospective monitoring in a family practice setting. PMID:21289786

  16. Adverse skeletal effects of drugs - beyond Glucocorticoids.

    PubMed

    O'Sullivan, Susannah; Grey, Andrew

    2015-01-01

    Osteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management. PMID:25039381

  17. Management of adverse effects of mood stabilizers.

    PubMed

    Murru, Andrea; Popovic, Dina; Pacchiarotti, Isabella; Hidalgo, Diego; León-Caballero, Jordi; Vieta, Eduard

    2015-08-01

    Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management.

  18. Adverse drug reactions: classification, susceptibility and reporting.

    PubMed

    Kaufman, Gerri

    2016-08-10

    Adverse drug reactions (ADRs) are increasingly common and are a significant cause of morbidity and mortality. Historically, ADRs have been classified as type A or type B. Type A reactions are predictable from the known pharmacology of a drug and are associated with high morbidity and low mortality. Type B reactions are idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality. Not all ADRs fit into type A and type B categories; therefore, additional categories have been developed. These include type C (continuing), type D (delayed use), and type E (end of use) reactions. Susceptibility to ADRs is influenced by age, gender, disease states, pregnancy, ethnicity and polypharmacy. Drug safety is reliant on nurses and other healthcare professionals being alert to the possibility of ADRs, working with patients to optimise medicine use and exercising vigilance in the reporting of ADRs through the Yellow Card Scheme. PMID:27507394

  19. Early Childhood Adversity and Pregnancy Outcomes

    PubMed Central

    Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

    2016-01-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  20. Adverse effects of differential parental attention1

    PubMed Central

    Sajwaj, Thomas E.; Pinkston, Susan; Cordua, Glenn; Jackson, Carolyn; Herbert, Emily W.; Pinkston, Elsie M.; Hayden, M. Loeman

    1973-01-01

    In two independent parent training projects (Kansas and Mississippi), mothers of deviant young children were observed to follow almost all child behaviors with attention. The mothers were then trained to use differential attention procedures to increase their child's appropriate behaviors and to decrease deviant behaviors. Contrary to expectations, the differential attention procedure produced substantial increases in deviant behavior for four of the children. This adverse effect was maintained over many sessions and was replicated in single organism, reversal designs. A fifth child showed no change. A sixth child showed some improvement. However, this effect was not recovered in a second application of differential attention, and the child became worse. The results underline the importance of subject generality in applied behavior analysis and strongly suggest that service programs using operant techniques must carefully evaluate their effects on behavior. PMID:16795386