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  1. Diagnosis of potential stressors adversely affecting benthic ...

    EPA Pesticide Factsheets

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

  2. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

  3. 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...

  4. 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…

  5. 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

  6. 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

  7. California's racial and ethnic minorities more adversely affected by asthma.

    PubMed

    Meng, Ying-Ying; Babey, Susan H; Hastert, Theresa A; Brown, E Richard

    2007-02-01

    In California, nearly 2.8 million adults and children (8%) had active asthma in 2003. Of Californians with active asthma, 890,000 are children (ages 0-17) and 1.8 million are adults (age 18 and above). The prevalence of active asthma varies by racial and ethnic group, with racial and ethnic minority groups affected more adversely by asthma. They are more likely to go to the emergency department for asthma care, miss more school and work days because of asthma, and have poorer health status. They are also more likely to lack access to health care and to live in conditions associated with asthma exacerbations. Among California children, the prevalence of active asthma varies by racial and ethnic groups-with the highest prevalence among African Americans (17%) and American Indians/Alaska Natives (17%), followed by whites (10%), Latinos (7%) and Asians (7%; Exhibit 1). Among adults, American Indians/Alaska Natives have the highest prevalence of active asthma (13%), followed by African Americans (10%), whites (9%), Asians (5%) and Latinos (5%). The National data similarly show that both African Americans and American Indians have higher current asthma prevalence rates than non- Hispanic whites.

  8. Toxins and adverse drug reactions affecting the equine nervous system.

    PubMed

    Dawson, Dominic R

    2011-12-01

    This article provides an overview of the more common toxins and adverse drug reactions, along with more rare toxins and reactions (Table 1), that result in neurologic dysfunction in horses. A wide variety of symptoms, treatments, and outcomes are seen with toxic neurologic disease in horses. An in-depth history and thorough physical examination are needed to determine if a toxin or adverse drug reaction is responsible for the clinical signs. Once a toxin or adverse drug reaction is identified, the specific antidote, if available, and supportive care should be administered promptly.

  9. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC 79-387... 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...

  10. Does prolonged breastfeeding adversely affect a child's nutritional status?

    PubMed

    Brakohiapa, L A; Yartey, J; Bille, A; Harrison, E; Quansah, E; Armar, M A; Kishi, K; Yamamoto, S

    1988-08-20

    In 202 children who visited a children's hospital in the city of Accra, Ghana, breastfeeding beyond the age of 19 months was found to be associated with malnutrition. The effect of weaning on food intake was then studied in 15 breastfed malnourished children in a rural community. Before weaning (complete cessation of breast-feeding) protein and energy intakes of all the malnourished children were about half those of 5 normal children. 10 of the malnourished children were weaned, and their intakes rose to the levels of the normal children; the 5 who continued breastfeeding maintained their low intakes. These results indicate that prolonged breastfeeding can reduce total food intake and thus predispose to malnutrition. They also suggest that in Ghana and other developing countries the proper weaning age may be about 18 months.

  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. 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.

  13. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    PubMed

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  14. Negative affect predicts adults' ratings of the current, but not childhood, impact of adverse childhood events.

    PubMed

    LaNoue, Marianna; Graeber, David A; Helitzer, Deborah L; Fawcett, Jan

    2013-10-01

    Adverse childhood events (ACE's) have been empirically related to a wide range of negative health and mental health outcomes. However, not all individuals who experience ACE's follow a trajectory of poor outcomes, and not all individuals perceive the impact of ACE's as necessarily negative. The purpose of this study was to investigate positive and negative affect as predictors of adults' ratings of both the childhood and adult impact of their childhood adversity. Self-report data on ACE experiences, including number, severity, and 'impact' were collected from 158 community members recruited on the basis of having adverse childhood experiences. Results indicated that, regardless of event severity and number of different types of adverse events experienced, high levels of negative affect were the strongest predictor of whether the adult impact of the adverse childhood events was rated as negative. All individuals rated the childhood impact of events the same. Implications are discussed.

  15. Blood rheology at term in normal pregnancy and in patients with adverse outcome events.

    PubMed

    von Tempelhoff, Georg-Friedrich; Velten, Eva; Yilmaz, Asli; Hommel, Gerhard; Heilmann, Lothar; Koscielny, Jürgen

    2009-01-01

    Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05

  16. Wood combustion particles induce adverse effects to normal and diseased airway epithelia.

    PubMed

    Krapf, Manuel; Künzi, Lisa; Allenbach, Sandrine; Bruns, Emily A; Gavarini, Ilaria; El-Haddad, Imad; Slowik, Jay G; Prévôt, André S H; Drinovec, Luka; Močnik, Griša; Dümbgen, Lutz; Salathe, Matthias; Baumlin, Nathalie; Sioutas, Constantinos; Baltensperger, Urs; Dommen, Josef; Geiser, Marianne

    2017-02-27

    Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components.

  17. Metabolically normal obese people are protected from adverse effects following weight gain.

    PubMed

    Fabbrini, Elisa; Yoshino, Jun; Yoshino, Mihoko; Magkos, Faidon; Tiemann Luecking, Courtney; Samovski, Dmitri; Fraterrigo, Gemma; Okunade, Adewole L; Patterson, Bruce W; Klein, Samuel

    2015-02-01

    BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation.

  18. Is there evidence that recent consolidation in the health insurance industry has adversely affected premiums?

    PubMed

    Kopit, William G

    2004-01-01

    James Robinson suggests that recent consolidation in the insurance market has been a cause of higher health insurance prices (premiums). Although the recent consolidation among health insurers and rising premiums are indisputable, it is unlikely that consolidation has had any adverse effect on premiums nationwide, and Robinson provides no data that suggest otherwise. Specifically, he does not present data showing an increase in concentration in any relevant market during the past few years, let alone any resulting increase in premiums. Health insurance consolidation in certain local markets could adversely affect premiums, but it seems clear that it is not a major national antitrust issue.

  19. Adverse event reporting and developments in radiation biology after normal tissue injury: International Atomic Energy Agency consultation

    SciTech Connect

    Chen Yuhchyau . E-mail: Yuhchyau_chen@urmc.rochester.edu; Trotti, Andy; Coleman, C. Norman; Machtay, Mitchell; Mirimanoff, Rene O.; Hay, John; O'Brien, Peter C.; El-Gueddari, Brahim; Salvajoli, Joao V.; Jeremic, Branislav

    2006-04-01

    Purpose: Recent research has enhanced our understanding of radiation injury at the molecular-cellular and tissue levels; significant strides have occurred in standardization of adverse event reporting in clinical trials. In response, the International Atomic Energy Agency, through its Division of Human Health and its section for Applied Radiation Biology and Radiotherapy, organized a consultation meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology, normal tissue reactions, and adverse event reporting. Methods and Materials: Representatives from cooperative groups of African Radiation Oncology Group, Curriculo Radioterapeutica Ibero Latino Americana, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada Clinical Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation Oncology Group held the meeting discussion. Results: Representatives of major radiotherapy groups/organizations and prominent leaders in radiotherapy discussed current understanding of normal tissue radiobiologic effects, the design and implementation of future clinical and translational projects for normal tissue injury, and the standardization of adverse-event reporting worldwide. Conclusions: The consensus was to adopt NCI comprehensive adverse event reporting terminology and grading system (CTCAE v3.0) as the new standard for all cooperative group trials. Future plans included the implementation of coordinated research projects focusing on normal tissue biomarkers and data collection methods.

  20. 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

  1. Mancozeb adversely affects meiotic spindle organization and fertilization in mouse oocytes.

    PubMed

    Rossi, Gianna; Palmerini, Maria Grazia; Macchiarelli, Guido; Buccione, Roberto; Cecconi, Sandra

    2006-07-01

    In this study the effects of mancozeb, a widely used ethylenebisdithiocarbamate fungicide, on mouse oocyte meiotic maturation and fertilization were analyzed. Oocyte cumulus cell-complexes were matured in vitro with or without increasing concentrations of the fungicide (from 0.001 to 1 microg/ml) that, due to its different stability in organic solvents and in water, was resuspended either in dimethyl sulfoxide or in culture medium. Although, about 95% of oocytes reached the metaphase II stage; mancozeb-exposed oocytes showed a dose-dependent increase of alterations in spindle morphology, and this negative effect was more evident when the fungicide was resuspended in culture medium. Under the latter culture condition, oocytes matured in the presence of 0.1 and 1 microg/ml mancozeb showed a significant reduction also in the formation of male and female pronuclei. These results indicate that mancozeb can adversely affect mammalian reproductive performance, likely by perturbing microtubular organization during meiotic maturation.

  2. 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.

  3. Catheterization of Intestinal Loops in Ruminants Does Not Adversely Affect Loop Function

    PubMed Central

    Inglis, G Douglas; Kastelic, John P; Uwiera, Richard R E

    2010-01-01

    Catheterized intestinal loops may be a valuable model to elucidate key components of the host response to various treatments within the small intestine of ruminants. We examined whether catheterizing ileal loops in sheep affected the overall health of animals and intestinal function, whether a bacterial treatment could be introduced into the loops through the catheters, and whether broad-spectrum antibiotics could sterilize the loops. Escherichia coli cells transformed to express the GFP gene were introduced readily into the loops through the catheters, and GFP E. coli cells were localized within the injected loops. Catheterized loops, interspaces, and intact ileum exhibited no abnormalities in tissue appearance or electrical resistance. Expression of the IFNγ, IL1α, IL4, IL6, IL12p40, IL18, TGFβ1, and TNFα cytokine genes did not differ significantly among the intact ileum, catheterized loops, and interspaces, nor did the expression of the gene for inducible nitric oxide synthase. Broad-spectrum antibiotics administered during surgery did not sterilize the loops or interspaces and did not substantively change the composition of the microbiota. However, antibiotics reduced the overall number of bacterial cells within the loop and the relative abundance of community constituents. We concluded that catheterization of intestinal loops did not adversely affect health or loop function in sheep. Furthermore, allowing animals to recover fully from surgery and to clear pharmaceuticals will remove any confounding effects due to these factors, making catheterized intestinal loops a feasible model for studying host responses in ruminants. PMID:21262134

  4. 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

  5. 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...

  6. Impact of High-Normal Blood Pressure Measured in Emergency Room on Adverse Cardiac Events in Acute Myocardial Infarction

    PubMed Central

    Yoon, Nam Sik; Ahn, Youngkeun; Kim, Jong Hyun; Chae, Shung Chull; Kim, Young Jo; Hur, Seung Ho; Seong, In Whan; Hong, Taek Jong; Choi, Donghoon; Cho, Myeong Chan; Kim, Chong Jin; Seung, Ki Bae; Chung, Wook Sung; Jang, Yang Soo; Cho, Jeong Gwan; Park, Seung Jung

    2012-01-01

    Background and Objectives Prehypertension according to JNC7 is common and is associated with increased vascular mortality. The importance of management in high-normal blood pressure (BP) is underemphasized. Subjects and Methods We analyzed major adverse cardiac events (MACEs) in the Korea Acute Myocardial Infarction Registry in normal BP (group I) and high-normal BP (group II) patients. Results Among 14871 patients, 159 (61±12.3 years, 122 males) satisfied the study indication. Six-month and one-year clinical follow-up rate was 88.9% and 85.8%, respectively. Group I had 78 patients (60.9±12.4 years). Group II had 81 patients (61.6±12.5 years). Demographics of patients were not different between groups. Treatment strategy was not different. Initial Thrombolysis in Myocardial Infarction flow grade 0 was less frequent in group II (n=32, 47.1%) than in group I (n=16, 21.9%) (p=0.001). Successful intervention rate was not different between group II (93.8%) and group I (97.1%) (p=0.590). Six-month MACE occurred in 3 patients in group I (4.4%) and 10 in group II (15.6%) (p=0.031). Compared with normal BP, the odds ratio for patients with high-normal BP was 1.147 (p=0.045, 95% confidence interval 1.011-1.402) for 6-month MACE. Conclusion Even though high-normal BP patients had a better baseline clinical status, the prognosis was poorer than patients with normal BP. Therapeutic BP target goal for the patients with acute myocardial infarction should be <140/90 mm Hg, which is recommended in JNC7. PMID:22701132

  7. 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.

  8. A systematic review of early life factors which adversely affect subsequent lung function.

    PubMed

    Kouzouna, A; Gilchrist, F J; Ball, V; Kyriacou, T; Henderson, J; Pandyan, A D; Lenney, W

    2016-09-01

    It has been known for many years that multiple early life factors can adversely affect lung function and future respiratory health. This is the first systematic review to attempt to analyse all these factors simultaneously. We adhered to strict a priori criteria for inclusion and exclusion of studies. The initial search yielded 29,351 citations of which 208 articles were reviewed in full and 25 were included in the review. This included 6 birth cohorts and 19 longitudinal population studies. The 25 studies reported the effect of 74 childhood factors (on their own or in combinations with other factors) on subsequent lung function reported as percent predicted forced expiration in one second (FEV1). The childhood factors that were associated with a significant reduction in future FEV1 could be grouped as: early infection, bronchial hyper-reactivity (BHR) / airway lability, a diagnosis of asthma, wheeze, family history of atopy or asthma, respiratory symptoms and prematurity / low birth weight. A complete mathematical model will only be possible if the raw data from all previous studies is made available. This highlights the need for increased cooperation between researchers and the need for international consensus about the outcome measures for future longitudinal studies.

  9. 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

  10. No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function.

    PubMed

    Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Sadoghi, Patrick; Wiedner, Maria; Haas, Franz; Leithner, Andreas; Windhager, Reinhard; Zwick, Ernst B

    2012-07-01

    The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow-up of 33 months (range, 7-59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0-23.0) underwent an instrumented three-dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow-up of 33 months.

  11. 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.

  12. 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

  13. Antioxidant-rich beetroot juice does not adversely affect acute neuromuscular adaptation following eccentric exercise.

    PubMed

    Clifford, Tom; Bell, Oliver; West, Daniel J; Howatson, Glyn; Stevenson, Emma J

    2017-04-01

    This study examined the effects of beetroot juice on the repeated bout effect (RBE) to eccentric exercise. Twenty-nine recreationally active males performed two bouts of 100-drop jumps, separated by 14-21 days. Using a double-blind, independent groups design, participants consumed either a higher dose beetroot juice (H-BT; 250 ml, n = 10), a lower dose beetroot juice (L-BT; 125 ml, n = 9) or an isocaloric placebo (PLA; 250 ml, n = 10) for 3 days after bout 1; no drinks were consumed after bout 2. Maximal isometric voluntary contraction (MIVC), countermovement jump (CMJ), pressure-pain threshold (PPT) and creatine kinase (CK) were measured pre, post, 24, 48 and 72 h following both bouts. In bout 2, CMJ and MIVC recovered quicker and CK activity was attenuated (versus bout 1) (P < 0.05) in all groups, demonstrating an RBE. At 24 h post bout 1, MIVC was 84.1 ± 16.1, 83.6 ± 11.6, 79.7 ± 15.1% relative to baseline values in the H-BT, L-BT and PLA groups, respectively; at 24 h post bout 2, MIVC recovered to 90.7 ± 13.7, 92.9 ± 6.9, 87.8 ± 6.9, in the H-BT, L-BT and PLA groups, respectively. These findings suggest that supplementation with antioxidant-rich beetroot juice does not adversely affect acute adaptations to a bout of eccentric exercise.

  14. Quality of life and functional capacity are adversely affected in osteoarthritis patients with neuropathic pain.

    PubMed

    Aşkın, Ayhan; Özkan, Ayten; Tosun, Aliye; Demirdal, Ümit Seçil; İsnaç, Fethi

    2017-03-01

    The aim of this study was to examine the neuropathic pain component of knee osteoarthritis (OA) patients and to investigate the relationship between neuropathic pain, disease stage, functional state, depression, anxiety, and quality of life. This study included 60 patients with knee OA. All demographic data and radiological results were recorded. Visual Analog Scale (VAS), Timed Up and Go Test, Chair Stand Test, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), PainDETECT questionnaire, DN4 questionnaire, Short form-36 questionnaire, and Hospital Anxiety Depression Scale were performed for each patient. Neuropathic pain was detected in 66.7% of patients based on the PainDETECT scale and in 46.7% of patients based on DN4 scale. VAS-resting, OA grade, WOMAC scores, and SF-scores showed a significant difference in patients that detected neuropathic pain with PainDETECT (p<0.05). Based on the DN4 scale, patients with neuropathic pain had significantly higher WOMAC scores and significantly lower SF-36 scores (p<0.05). The PainDETECT questionnaire scores showed positive correlations with Timed Up-and-go Test, VAS-resting, WOMAC scores, Hospital Anxiety Depression Scale scores, and a negative correlation with all SF-36 scores (p<0.05). DN4 questionnaire scores showed a negative correlation with SF-36 scores and positive correlation with WOMAC scores (p<0.05). To conclude, it should be kept in mind that patients with knee OA who describe intense pain may have a neuropathic component involved in the clinical condition. Quality of life and functional capacity are adversely affected in patients with knee OA who have neuropathic pain. This should be taken into account while planning the treatment of these patients.

  15. 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

  16. 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...

  17. 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...

  18. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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...

  19. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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...

  20. 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...

  1. 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.

  2. 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.…

  3. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  4. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  5. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  6. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  7. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  8. 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...

  9. 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...

  10. 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...

  11. Does Employment-Related Resilience Affect the Relationship between Childhood Adversity, Community Violence, and Depression?

    PubMed

    Welles, Seth L; Patel, Falguni; Chilton, Mariana

    2017-04-01

    Depression is a barrier to employment among low-income caregivers receiving Temporary Assistance for Needy Families (TANF), and adverse childhood experiences (ACEs) and exposure to community violence (ECV) are often associated with depression. Using baseline data of 103 TANF caregivers of young children of the Building Wealth and Health Network Randomized Controlled Trial Pilot, this study investigated associations of two forms of employment-related resilience-self-efficacy and employment hope-with exposure to adversity/violence and depression, measured by the Center for Epidemiologic Studies Depression (CES-D) short form. Using contingency table analysis and regression analysis, we identified associations between ACEs and depression [OR = 1.70 (1.25-2.32), p = 0.0008] and having high levels of ECV with a 6.9-fold increased risk for depression when compared with those without ECV [OR = 6.86 (1.43-33.01), p = 0.02]. While self-efficacy and employment hope were significantly associated with depression, neither resilience factor impacted the association of ACE level and depression, whereas self-efficacy and employment hope modestly reduced the associations between ECV and depression, 13 and 16%, respectively. Results suggest that self-efficacy and employment hope may not have an impact on the strong associations between adversity, violence, and depression.

  12. Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival.

    PubMed

    Marean, Amber; Graf, Amanda; Zhang, Ying; Niswander, Lee

    2011-09-15

    Neural tube defects (NTDs), a common birth defect in humans, result from the failure of the embryonic neural tube (NT) to close properly. NT closure is a complex, poorly understood morphogenetic process influenced by genes and environment. The most effective environmental influence in decreasing the risk for NTDs is folic acid (FA) fortification and supplementation, and these findings led to the recommendation of periconceptual FA intake and mandatory fortification of the US grain supply in 1998. To explore the relationship between genetics and responsiveness to FA supplementation, we used five mouse NTDs models-Zic2, Shroom3, Frem2, Grhl2 (Grainyhead-like 2) and L3P (Line3P)-and a long-term generational FA supplementation scheme. Contrary to expectations, we find that three genetic mutants respond adversely to FA supplementation with increased incidence of NTDs in homozygous mutants, occurrence of NTDs in heterozygous embryos and embryonic lethality prior to NT closure. Because of these unexpected responses, we examined NTD risk after short-term FA supplementation. Our results indicate that, for the same genetic allele, NTD risk can depend on the length of FA exposure. Our data indicate that, depending on the gene mutation, FA supplementation may adversely influence embryonic development and NT closure.

  13. Does low-normal serum TSH level adversely impact cognition in elderly adults and might methimazole therapy improve outcomes?

    PubMed

    Chachamovitz, Dhiãnah Santini de Oliveira; Vigário, Patrícia Dos Santos; Silva, Silvana Oliveira E; Teixeira, Letícia B B de Mello; Fagundes, Michele Lopes; Vaisman, Mário; Teixeira, Patrícia de F Dos S

    2016-05-31

    Serum thyroid stimulating hormone (TSH) levels increase with age. This elevation has been associated with better outcomes in very elderly subjects; however, little is known about the relationship between TSH below the lower limit of the reference range and health-related outcomes. Here, we investigated the association between cognitive impairment or depressive symptoms and low-normal serum TSH (<1.0 μIU/mL, in the reference range) in elderly subjects and whether the use of methimazole in subjects without dementia but with low-normal TSH could affect cognition or depressive symptoms. From 293 healthy adults ≥65 years old with normal TSH included in the sectional phase, only subjects without dementia were prospectively analyzed: 1) TSH ≥1.0 μIU/mL (observation; untreated); 2) TSH <1.0 μIU/mL (observation; untreated); and 3) TSH <1.0 μIU/mL (methimazole therapy). Cognition was assessed, using the Mini Mental State Examination (MMSE) and depressive symptoms (at MMSE ≥ 13) by the Geriatric Depression Scale (GDS). Age >80 years was the sole independent factor associated with dementia (OR=2.89; confidence interval [CI] 1.72-4.86; p<0.01). Prospectively, 93 completed follow-up, with 7.5% (7) receiving methimazole intervention. Untreated subjects with lower TSH showed the greatest declines in MMSE scores during follow-up that was not observed in those with serum TSH ≥1.0 μIU/mL. Lower MMSE score reductions were associated with elderly subjects receiving methimazole. There were no significant changes in depressive symptoms and GDS scores among those with serum TSH <1.0 μIU/mL. In this study, low-normal TSH was not associated with higher prevalence of dementia. However, in elderly subjects without dementia, low TSH was associated with worsening cognition.

  14. 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…

  15. Lead-induced oxidative stress adversely affects health of the occupational workers.

    PubMed

    Khan, D A; Qayyum, S; Saleem, S; Khan, F A

    2008-10-01

    Lead is a persistent toxic metal and associated with impairment of various body functions in occupational workers. The main objective was to determine the lead-induced oxidative stress and adverse health effects by biochemical markers in industrial workers. One hundred and forty-eight males consisting of 87 lead-exposed industrial workers and 61 controls were included. Blood lead level (BLL) was determined on a 3010B ESA lead analyzer. Blood complete counts were done on a hematology analyzer. Biochemical markers including serum uric acid, urea, creatinine, phosphate, alanine aminotransferase (ALT), and gamma glutamyltransferase (GGT) were measured on a Selectra E auto analyzer. Serum malondialdehyde (MDA) was measured spectrophotometrically and C-reactive protein (CRP) on Immulite-1000. Results revealed that lead-exposed workers had significantly high BLLs, median (range), 29.1 (9.0-61.1) microg/dL compared with controls, 8.3 (1.0-21.7) microg/dL. Oxidative stress (MDA, GGT) and inflammatory markers (high-sensitivity CRP) were significantly increased (P < or = 0.05). Blood pressure was raised, whereas hemoglobin was decreased in exposed group (P < or = 0.002). Serum urea, uric acid, phosphate, and ALT were significantly raised in lead-exposed workers (P < or = 0.001). Serum albumin, total proteins, and glomerular filtration rate (GFR) were decreased. Blood lead showed a significant positive correlation with serum GGT (r = 0.63), MDA (r = 0.71), CRP (r = 0.75), urea (r = 0.34), creatinine (r = 0.51), and uric acid (r = 0.29) (P < or = 0.01). It is concluded that lead exposure increases oxidative stress that correlates with adverse changes in hematological, renal, and hepatic function in the occupational workers. Elevated blood lead has positive correlation with oxidative stress, inflammatory and biochemical markers that might be used to detect impairment in the body function in lead exposed workers.

  16. Diagnosis of potential stressors adversely affecting benthic invertebrate communities in Greenwich Bay, Rhode Island, USA

    EPA Science Inventory

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was imp...

  17. 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.

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

    PubMed

    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

    2011-09-01

    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.

  19. 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

    2016-11-03

    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.

  20. Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

    PubMed

    Song, Yu-Zhe; Han, Fu-Jun; Liu, Min; Xia, Cheng-Cheng; Shi, Wei-Yan; Dong, Li-Hua

    2015-01-01

    The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results.

  1. Exposure to zidovudine adversely affects mitochondrial turnover in primary T cells.

    PubMed

    Wallace, Zoë R; Sanderson, Sharon; Simon, Anna Katarina; Dorrell, Lucy

    2016-09-01

    Zidovudine (ZDV) is a widely used component of antiretroviral therapy (ART) in resource-limited settings, despite its known adverse effects, which include mitochondrial toxicity in muscle, liver and adipose tissue. It has also been associated with impaired immunological recovery. We hypothesised that ZDV might impair mitochondrial health and survival of primary T cells. We performed a cross-sectional analysis of mitochondrial function, mitophagy and susceptibility to apoptosis in healthy donor primary T cells after exposure to ZDV in vitro, together with T cells from patients who were virologically suppressed on ZDV-containing ART regimens for ≥1 year and age-matched subjects receiving non-ZDV ART regimens. The proportion of T cells expressing mitochondrial reactive oxygen species (mtROS) was significantly higher after in vitro (CD4(+) T cells and CD8(+) T cells) and in vivo (CD4(+) T cells) exposure to ZDV than other antiretroviral agents. We did not detect any effect of ZDV on mitophagy, as indicated by change in autophagic flux. However, spontaneous apoptosis, indicated by upregulation of caspase-3 was greater in ZDV-exposed T cells. In conclusion, ZDV exposure was associated with impaired mitochondrial turnover and increased susceptibility to apoptosis in T cells. These mechanisms could contribute to sub-optimal immune reconstitution.

  2. 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

  3. Maternal and young child nutrition adversely affected by external shocks such as increasing global food prices.

    PubMed

    Darnton-Hill, Ian; Cogill, Bruce

    2010-01-01

    Rising food prices, resulting from the ongoing global economic crisis, fuel price volatility, and climate change, have an adverse impact upon the poor, especially those in food-importing, resource-limited countries. The conventional approach by large organizations has been to advocate for increased staple crop yields of mainly cereals. High food prices are predicted to continue to at least 2015. Past shocks and their known impacts upon nutrition were reviewed. Price instability and increases have long been an existing global problem, which has been exacerbated by recent macroeconomic shocks such as acute emergencies due to war and civil strife, acute climatic events, increase in food prices, fuel price volatility, dysfunction of the global financial systems, long-term climate change, and the emergence of failed states. The FAO estimated that there were 815 million "hungry" people in 2006, with a now additional 75-135 million with increased vulnerability, and currently it is estimated that there are one billion people at risk of food insecurity. The shocks initially compromise maternal and child nutrition, mainly through a reduction in dietary quality and an increase in micronutrient deficiencies and concomitant increases in infectious disease morbidity and mortality. A further reduction in the quantity of diet may follow with greater underweight and wasting. Recent macroeconomic shocks have greatly increased the number of people who are vulnerable to hunger in developing countries. Nutritional surveillance systems need to be strengthened and expanded to inform policy decisions.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. 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.

  6. 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…

  7. Does maternal prenatal stress adversely affect the child's learning and memory at age six?

    PubMed

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

    2006-12-01

    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 boys, 62 girls, Age: M=6.7 years, SD=8.4 months), with the Test of Memory and Learning (TOMAL). Maternal stress levels were determined three times during pregnancy by self-report questionnaires. Furthermore, maternal saliva cortisol samples were used as a measure of hypothalamus-pituitary-adrenal axis functioning. Results of hierarchical multivariate regression analyses showed that maternal life events measured during the first part of pregnancy were negatively associated with the child's attention/concentration index, while controlling for overall IQ, gender, and postnatal stress. No associations were found between prenatal maternal cortisol and the offspring's learning and memory.

  8. Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations.

    PubMed

    Roepke, Troy A; Snyder, Mark J; Cherr, Gary N

    2005-01-26

    Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>E2>EE2>DDD>BisA>P4>E1>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng

  9. Early-life adversity accelerates cellular ageing and affects adult inflammation: Experimental evidence from the European starling

    PubMed Central

    Nettle, Daniel; Andrews, Clare; Reichert, Sophie; Bedford, Tom; Kolenda, Claire; Parker, Craig; Martin-Ruiz, Carmen; Monaghan, Pat; Bateson, Melissa

    2017-01-01

    Early-life adversity is associated with accelerated cellular ageing during development and increased inflammation during adulthood. However, human studies can only establish correlation, not causation, and existing experimental animal approaches alter multiple components of early-life adversity simultaneously. We developed a novel hand-rearing paradigm in European starling nestlings (Sturnus vulgaris), in which we separately manipulated nutritional shortfall and begging effort for a period of 10 days. The experimental treatments accelerated erythrocyte telomere attrition and increased DNA damage measured in the juvenile period. For telomere attrition, amount of food and begging effort exerted additive effects. Only the combination of low food amount and high begging effort increased DNA damage. We then measured two markers of inflammation, high-sensitivity C-reactive protein and interleukin-6, when the birds were adults. The experimental treatments affected both inflammatory markers, though the patterns were complex and different for each marker. The effect of the experimental treatments on adult interleukin-6 was partially mediated by increased juvenile DNA damage. Our results show that both nutritional input and begging effort in the nestling period affect cellular ageing and adult inflammation in the starling. However, the pattern of effects is different for different biomarkers measured at different time points. PMID:28094324

  10. Alkaline decontamination of sputum specimens adversely affects stability of mycobacterial mRNA.

    PubMed Central

    Desjardin, L E; Perkins, M D; Teixeira, L; Cave, M D; Eisenach, K D

    1996-01-01

    Reverse transcriptase PCR (RT-PCR) is an important tool for Mycobacterium tuberculosis research and diagnostics. A standard procedure using N-acetyl-L-cysteine (NALC) and NaOH has been widely adopted for digestion and decontamination of sputum specimens for mycobacterial culture. The objective of this study was to determine the compatibility of this method with the recovery of RNA for RT-PCR assays. Nineteen sputum specimens were collected from smear-positive, pretreatment tuberculosis patients. After homogenization with NALC and glass beads, specimens were further processed by the addition of either NaOH, as per the standard decontamination protocol, or phosphate buffer. RNA was prepared by using a modified guanidine-phenol extraction method developed specifically for sputum sediments. DNA was isolated from the same specimens. Reverse transcriptions of alpha antigen (85B protein) mRNA and 16S rRNA were performed together, and aliquots were removed for separate PCRs. In all specimens, the 85B mRNA target was greatly diminished by treatment with NaOH; however, the 16S rRNA target remained unaffected. Storing sputum specimens for 48 h at 4 degrees C before processing did not seem to affect the integrity or yield of RNA; however, some degradation occurred by 72 h. Data suggest that the NaOH-NALC method for processing sputum samples is not suitable for detecting mRNA targets in RT-PCR assays. PMID:8880495

  11. Fibrinolysis inhibitors adversely affect remodeling of tissues sealed with fibrin glue.

    PubMed

    Krishnan, Lissy K; Vijayan Lal, Arthur; Uma Shankar, P R; Mohanty, Mira

    2003-01-01

    Experiments have been carried out to determine if aprotinin and epsilon -amino caproic acid increases the quality of Fibrin glue. A rat model was used for tissues such as liver and skin while rabbits were used for application of glue in dura mater. Apposition of all the tissues, glued with fibrin was found to be good and remnants of the polymerized fibrin were seen even on the seventh day of application, though inhibitors were not incorporated with the glue. In skin, excessive amounts of fibrin remained as a result of addition of aprotinin and epsilon -amino caproic acid, as compared to the glue applied without any inhibitor. After dural sealing, the wound repair and new bone formation at craniotomy site progressed well in the fibrin glue applied area as compared to the commercially available glue that contained aprotinin. The adhesive strength of the glue without or with fibrinolysis inhibitors was found to be similar, after 1h grafts on rat back. The observations from this study suggests that the use of aprotinin with fibrin glue may not be required because, even liver tissue that is known to have high fibrinolytic activity was sealed and repaired well in the absence of plasminogen inhibitors. On the other hand, it was found that if inhibitors were added, nondegraded matrix remained in the tissue even after 15 days and affected migration of repair cells. Thus, the inhibition of fibrinolysis after fibrin glue application is found detrimental to wound healing.

  12. 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

  13. Glyphosate Adversely Affects Danio rerio Males: Acetylcholinesterase Modulation and Oxidative Stress.

    PubMed

    Lopes, Fernanda Moreira; Caldas, Sergiane Souza; Primel, Ednei Gilberto; da Rosa, Carlos Eduardo

    2017-04-01

    It has been demonstrated that glyphosate-based herbicides are toxic to animals. In the present study, reactive oxygen species (ROS) generation, antioxidant capacity against peroxyl radicals (ACAP), and lipid peroxidation (LPO), as well as the activity and expression of the acetylcholinesterase (AChE) enzyme, were evaluated in Danio rerio males exposed to 5 or 10 mg/L of glyphosate for 24 and 96 h. An increase in ACAP in gills after 24 h was observed in the animals exposed to 5 mg/L of glyphosate. A decrease in LPO was observed in brain tissue of animals exposed to 10 mg/L after 24 h, while an increase was observed in muscle after 96 h. No significant alterations were observed in ROS generation. AChE activity was not altered in muscles or brains of animals exposed to either glyphosate concentration for 24 or 96 h. However, gene expression of this enzyme in the brain was reduced after 24 h and was enhanced in both brain and muscle tissues after 96 h. Thus, contrary to previous findings that had attributed the imbalance in the oxidative state of animals exposed to glyphosate-based herbicides to surfactants and other inert compounds, the present study demonstrated that glyphosate per se promotes this same effect in zebrafish males. Although glyphosate concentrations did not alter AChE activity, this study demonstrated for the first time that this molecule affects ache expression in male zebrafish D. rerio.

  14. Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis

    PubMed Central

    Song, Yu-Zhe; Han, Fu-Jun; Liu, Min; Xia, Cheng-Cheng; Shi, Wei-Yan; Dong, Li-Hua

    2015-01-01

    The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31–3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97–1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49–3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02–1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26–0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results. PMID:26091483

  15. 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.

  16. 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

  17. Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-{beta}1

    SciTech Connect

    Schmid, Stephan A. . E-mail: leoni.kunz-schughart@oncoray.de; Gaumann, Andreas; Wondrak, Marit; Eckermann, Christoph; Schulte, Stephanie; Mueller-Klieser, Wolfgang; Wheatley, Denys N.; Kunz-Schughart, Leoni A.

    2007-07-15

    When lactate accumulation in a tumor microenvironment reaches an average concentration of 10-20 mM, it tends to reflect a high degree of malignancy. However, the hypothesis that tumor-derived lactate has a number of partially adverse biological effects on malignant and tumor-associated host cells requires further evidence. The present study attempted to evaluate the impact of lactate on the process of angiogenesis, in particular on the formation of tubular structures. The endothelial cell (EC) network in desmoplastic breast tumors is primarily located in areas of reactive fibroblastic stroma. We employed a fibroblast-endothelial cell co-culture model as in vitro angiogenesis system normally producing florid in vitro tubule formation to analyze this situation. In contrast to previous studies, we found that lactate significantly reduces EC network formation in a dose-dependent manner as quantified by semi-automated morphometric analyses following immunohistochemical staining. The decrease in CD31-positive tubular structures and the number of intersections was independent of VEGF supplementation and became more pronounced in the presence of protons. The number of cells, primarily of the fibroblast population, was reduced but cell loss could not be attributed to a decrease in proliferative activity or pronounced apoptotic cell death. Treatment with 10 mM lactate was accompanied by enhanced mRNA expression and release of TGF-{beta}1, which also shows anti-angiogenic activity in the model. Both TGF-{beta}1 and lactate induced myofibroblastic differentiation adjacent to the EC tubular structures. The lactate response on the EC network was diminished by TGF-{beta}1 neutralization, indicating a causal relationship between lactate and TGF-{beta}1 in the finely tuned processes of vessel formation and maturation which may also occur in vivo within tumor tissue.

  18. 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.

  19. Does epidural analgesia affect the rate of spontaneous obstetric lacerations in normal births?

    PubMed

    Albers, Leah L; Migliaccio, Laura; Bedrick, Edward J; Teaf, Dusty; Peralta, Patricia

    2007-01-01

    The precise relationship between epidural use and genital tract lacerations in normal childbirth is unclear. Data from a clinical trial on measures to lower genital tract trauma in vaginal birth were used for a secondary analysis. The goal was to assess whether epidurals affect the rate of spontaneous obstetric lacerations in normal vaginal births. Maternal characteristics and intrapartum variables were compared in women who did and did not use an epidural in labor, and also in those with and without any sutured lacerations following vaginal birth. Variables that were statistically different in both cases were entered into regression equations for simultaneous adjustment. Epidural use was not an independent predictor of sutured lacerations. Predictors of sutured lacerations included nulliparity, a prolonged second stage, being non-Hispanic white, and an infant birthweight greater than 4000 grams. Elements of midwifery management need further research.

  20. Normal adult aging and the contextual influences affecting speech and meaningful sound perception.

    PubMed

    Aydelott, Jennifer; Leech, Robert; Crinion, Jennifer

    2010-12-01

    It is widely accepted that hearing loss increases markedly with age, beginning in the fourth decade ISO 7029 (2000). Age-related hearing loss is typified by high-frequency threshold elevation and associated reductions in speech perception because speech sounds, especially consonants, become inaudible. Nevertheless, older adults often report additional and progressive difficulties in the perception and comprehension of speech, often highlighted in adverse listening conditions that exceed those reported by younger adults with a similar degree of high-frequency hearing loss (Dubno, Dirks, & Morgan) leading to communication difficulties and social isolation (Weinstein & Ventry). Some of the age-related decline in speech perception can be accounted for by peripheral sensory problems but cognitive aging can also be a contributing factor. In this article, we review findings from the psycholinguistic literature predominantly over the last four years and present a pilot study illustrating how normal age-related changes in cognition and the linguistic context can influence speech-processing difficulties in older adults. For significant progress in understanding and improving the auditory performance of aging listeners to be made, we discuss how future research will have to be much more specific not only about which interactions between auditory and cognitive abilities are critical but also how they are modulated in the brain.

  1. Normal Adult Aging and the Contextual Influences Affecting Speech and Meaningful Sound Perception

    PubMed Central

    Aydelott, Jennifer; Leech, Robert; Crinion, Jennifer

    2010-01-01

    It is widely accepted that hearing loss increases markedly with age, beginning in the fourth decade ISO 7029 (2000). Age-related hearing loss is typified by high-frequency threshold elevation and associated reductions in speech perception because speech sounds, especially consonants, become inaudible. Nevertheless, older adults often report additional and progressive difficulties in the perception and comprehension of speech, often highlighted in adverse listening conditions that exceed those reported by younger adults with a similar degree of high-frequency hearing loss (Dubno, Dirks, & Morgan) leading to communication difficulties and social isolation (Weinstein & Ventry). Some of the age-related decline in speech perception can be accounted for by peripheral sensory problems but cognitive aging can also be a contributing factor. In this article, we review findings from the psycholinguistic literature predominantly over the last four years and present a pilot study illustrating how normal age-related changes in cognition and the linguistic context can influence speech-processing difficulties in older adults. For significant progress in understanding and improving the auditory performance of aging listeners to be made, we discuss how future research will have to be much more specific not only about which interactions between auditory and cognitive abilities are critical but also how they are modulated in the brain. PMID:21307006

  2. Assembly and deacetylation of N-acetylglucosaminyl-plasmanylinositol in normal and affected paroxysmal nocturnal hemoglobinuria cells

    SciTech Connect

    Hirose, Shinichi; Ravi, Lakshmeswari; Medof, M.D. ); Hazra, S.V. )

    1991-05-01

    Decay-accelerating factor (DAF) is anchored in cell membranes by a glycosyl-plasmanylinositol (GPI) moiety that is transferred to it en bloc in the rough endoplasmic reticulum. To analyze the biochemical reactions involved in preassembly of this structure, a human hematopoietic cell-free system was employed. Incubation of cell extracts with UDP-({sup 3}H)GlcNAc and butanol partitioning of reaction mixtures yielded two products similar in TLC mobility to intermediates described in Trypanoxoma brucei. Both species were sensitive to Bacillus thuringiensis phosphatidylinositol-specific phospholipase C, indicative of association of ({sup 3}H)GlcNAc label with a plasmanylinositol-containing acceptor. Kinetic and pulse-chase experiments indicated that the slower-migrating species was a product of the faster and that it, but not the faster, was sensitive to both GPI-specific phospholipase D and nitrous acid deamination, consistent with conversion of GlcNAc- to GlcN-plasmanylinositol. Lysates of normal and of affected blood leukocytes from two paroxysmal nocturnal hemoglobinuria (PNH) patients supported assembly of the two intermediates within 1 min. Thus, the initial enzymes mediating human GPI-anchor assembly are GlcNAc-plasmanylinositol transferase and GlcNAc-plasmanylinositol deacetylase, their substrates contain plasmanylinositols, and the products of their activities are normal in affected PNH cells.

  3. Cdk4 deficiency inhibits skin tumor development but does not affect normal keratinocyte proliferation.

    PubMed

    Rodriguez-Puebla, Marcelo L; Miliani de Marval, Paula L; LaCava, Margaret; Moons, David S; Kiyokawa, Hiroaki; Conti, Claudio J

    2002-08-01

    Most human tumors have mutations that result in deregulation of the cdk4/cyclin-Ink4-Rb pathway. Overexpression of D-type cyclins or cdk4 and inactivation of Ink4 inhibitors are common in human tumors. Conversely, lack of cyclin D1 expression results in significant reduction in mouse skin and mammary tumor development. However, complete elimination of tumor development was not observed in these models, suggesting that other cyclin/cdk complexes play an important role in tumorigenesis. Here we described the effects of cdk4 deficiency on mouse skin proliferation and tumor development. Cdk4 deficiency resulted in a 98% reduction in the number of tumors generated through the two-stage carcinogenesis model. The absence of cdk4 did not affect normal keratinocyte proliferation and both wild-type and cdk4 knockout epidermis are equally affected after topical treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting in epidermal hyperplasia. In similar fashion, cdk4 knockout keratinocytes proliferated well in an in vivo model of wound-induced proliferation. Biochemical studies in mouse epidermis showed that cdk6 activity increased twofold in cdk4-deficient mice compared to wild-type siblings. These results suggest that therapeutic approaches to inhibit cdk4 activity could provide a target to inhibit tumor development with minimal or no effect in normal tissue.

  4. High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice.

    PubMed

    Wang, Yang; Dellatore, Peter; Douard, Veronique; Qin, Ling; Watford, Malcolm; Ferraris, Ronaldo P; Lin, Tiao; Shapses, Sue A

    2016-07-01

    Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects.

  5. Transformation of cytogenetically normal chronic myelomonocytic leukaemia to an acute myeloid leukaemia and the emergence of a novel +13, +15 double trisomy resulting in an adverse outcome.

    PubMed

    McGrattan, Peter; Humphreys, Mervyn; Hull, Donald; McMullin, Mary F

    2007-09-01

    A 58-year-old man was admitted with symptoms of lethargy and easy bruising for four months duration. Peripheral blood (PB) analysis revealed a white blood cell count (WBC) of 15.9 x 10(9)/l with monocytes 5.4 x 10(9)/l. Bone marrow (BM) was hypercellular with 15% blasts, monocytosis and trilineage dysplasia. Conventional cytogenetic analysis (G-banding) detected an apparently normal male karyotype (46,XY). A diagnosis of chronic myelomonocytic leukaemia (CMML) was made. After 3 years, PB analysis revealed a WBC count of 22 x 10(9)/l and a predominance of blasts. BM aspirate analysis also revealed 89% myeloid blasts and G-banding detected the emergence of an abnormal clone harbouring an extra copy of chromosomes 13 and 15. A diagnosis of disease transformation to acute myeloid leukaemia (AML) was made. Post chemotherapy BM aspirate was very hypocellular and the abnormal +13, +15 clone was still present suggesting primary refractory disease. A second course of chemotherapy was only administered for 24 hours due to complications. The abnormal +13, +15 clone was still present and it was decided that no further treatment apart from palliative care could be offered. The patient died 11 weeks later, five months after AML transformation. This is the first description of a cytogenetically normal CMML patient transforming to AML with the emergence of a unique +13, +15 double trisomy resulting in an adverse outcome.

  6. Maternal interaction style in affective disordered, physically ill, and normal women.

    PubMed

    Hamilton, E B; Jones, M; Hammen, C

    1993-09-01

    Affective style (AS) and communication deviance (CD) have been suggested as markers of dysfunctional family environments that may be associated with psychiatric illness. Studies have focused mainly on parental responses during family interactions when an offspring is the identified patient. The present study is unique in examining AS and CD in mothers with unipolar depression, bipolar disorder, or chronic physical illness, and in normal controls. The sample consisted of 64 mothers with children ages 8 to 16. Unipolar mothers were more likely to show negative AS than were any other maternal group. There were no group differences for CD. Chronic stress, few positive life events, and single parenting were associated with AS. CD was associated solely with lower socioeconomic status. Results suggest that dysfunctional interactions are determined not only by maternal psychopathology, but also by an array of contextual factors that are related to the quality of the family environment.

  7. Effect of 2% Chlorhexidine Digluconate on the Bond Strength to Normal versus Caries-Affected Dentin

    PubMed Central

    Komori, Paula C. P.; Pashley, David H.; Tjäderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; de Goes, Mario Fernando; Wang, Linda; Carrilho, Marcela R.

    2013-01-01

    SUMMARY This study evaluated the effect of 2% chlorhexidine digluconate (CHX) used as a therapeutic primer on the long-term bond strengths of two etch-and-rinse adhesives to normal (ND) and caries-affected (CAD) dentin. Forty extracted human molars with coronal carious lesions, surrounded by normal dentin, were selected for this study. Flat surfaces of two types of dentin (i.e. ND and CAD) were prepared with a water-cooled high speed diamond disc, and then acid-etched, rinsed and air-dried. In control groups, dentin was re-hydrated with distilled water, blot-dried and bonded with a three-step (Scotchbond Multi-Purpose-MP) or a two-step (Single Bond 2-SB) etch-and-rinse adhesive. In experimental groups, dentin was re-hydrated with 2% CHX (60 s), blot-dried and bonded with the same adhesives. Resin composite build-ups were made. Specimens were prepared for microtensile bond testing in accordance with the non-trimming technique and then tested either immediately or after 6-month storage in artificial saliva. Data were analyzed by ANOVA/Bonferroni tests (α = 0.05). CHX did not affect the immediate bond strength to ND or CAD (p>0.05). CHX treatment significantly lowered the loss of bond strength after 6 months seen in control bonds for ND (p<0.05), but it did not alter the bond strength of CAD (p>0.05). Application of MP on CHX-treated ND or CAD produced bonds that did not change over 6 months of storage. PMID:19363971

  8. Pre-operative psychological distress does not adversely affect functional or mental health gain after primary total hip arthroplasty.

    PubMed

    Hossain, Munier; Parfitt, Daniel J; Beard, David J; Darrah, Clare; Nolan, John; Murray, David W; Andrew, John G

    2011-01-01

    Preoperative psychological distress has been reported to predict poor outcome and patient dissatisfaction after total hip arthroplasty (THA). The purpose of this study was to investigate if pre-operative psychological distress was associated with adverse functional outcome after primary THR. We analysed the database of a prospective multi-centre study undertaken between January 1999 and January 2002. We recorded the Oxford Hip Score (OHS) and SF36 score preoperatively and up to five years after surgery for 1055 patients. We dichotomised the patients into the mentally distressed (Mental Health Scale score - MHS =56) and the not mentally distressed (MHS >56) groups based on their pre-operative MHS of the SF36. 762 (72.22%). Patients (595 not distressed and 167 distressed) were followed up at 5 years. Both pre and post-operative OHS and SF-36 scores were significantly worse in the distressed group (both p<0.001). However, both groups experienced statistically significant improvement in OHS and MHS, which was maximal at 1 year after surgery and was maintained over the follow up (p=0.00). There was a substantial improvement in mental distress in patients who reported mental distress prior to surgery. The results suggest that pre-operative psychological distress did not adversely compromise functional outcome gain after THA. Despite having worse absolute values both pre and post operatively, patients with mental distress did not have any less functional gain from THA as measured by improvement in OHS.

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

    PubMed

    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.

  10. 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

  11. Normal water irrigation as an alternative to effluent irrigation in improving rice grain yield and properties of a paper mill effluent affected soil.

    PubMed

    Boruah, D; Hazarika, S

    2010-07-01

    Rice crop (var. Luit) was grown under controlled conditions in paper mill effluent contaminated soil and irrigated with undiluted paper mill effluent as well as normal water and compared the results against a control treatment consisting of similar unaffected soil irrigated with normal water. The effluent was alkaline (pH 7.5), containing high soluble salts (EC 2.93 dS m(-1)), chloride (600 mg L(-1)) and total dissolved solids (1875 mg L(-1)). At maximum tillering (MT) stage effluent irrigation significantly (P < 0.05) reduced the leaf numbers per hill and leaf area by 19.8 and 36.4 %, respectively. Tiller number and maximum root length were reduced by 19.3% and 12.5%, respectively at fifty percent flowering (FF) stage. Effluent irrigated crop recorded significant reduction in the dry matter production (17.5-24.9%) and grain yield (19%). Unfilled grain was increased by 10.7%. Higher concentration of sodium, calcium and magnesium in the effluent irrigated soil affected K uptake. Available soil P was lowest while available N, K, S and exchangeable and water soluble Na, K, Ca, Mg were highest in effluent irrigated soil. Chloride content found to increase (3-7 folds) while microbial biomass carbon reduced (10-37%). The adverse effect of the paper mill effluent on the crop as well as on the affected soil could be reduced significantly through normal water irrigation.

  12. Dipeptidyl Peptidase IV Inhibition Does Not Adversely Affect Immune or Virological Status in HIV Infected Men And Women: A Pilot Safety Study

    PubMed Central

    Goodwin, Scott R.; Reeds, Dominic N.; Royal, Michael; Struthers, Heidi; Laciny, Erin

    2013-01-01

    Context: People infected with HIV have a higher risk for developing insulin resistance, diabetes, and cardiovascular disease than the general population. Dipeptidyl peptidase IV (DPP4) inhibitors are glucose-lowering medications with pleiotropic actions that may particularly benefit people with HIV, but the immune and virological safety of DPP4 inhibition in HIV is unknown. Objective: DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive adults. Design: This was a randomized, placebo-controlled, double-blind safety trial of sitagliptin in HIV-positive adults. Setting: The study was conducted at an academic medical center. Participants: Twenty nondiabetic HIV-positive men and women (9.8 ± 5.5 years of known HIV) taking antiretroviral therapy and with stable immune (625 ± 134 CD4+ T cells per microliter) and virological (<48 copies HIV RNA per milliliter) status. Intervention: The intervention included sitagliptin (100 mg/d) vs matching placebo for up to 24 weeks. Main Outcome Measures: CD4+ T cell number and plasma HIV RNA were measured every 4 weeks; fasting serum regulated upon activation normal T-cell expressed and secreted (RANTES), stromal derived factor (SDF)-1α, Soluble TNF receptor II, and oral glucose tolerance were measured at baseline, week 8, and the end of study. ANOVA was used for between-group comparisons; P < .05 was considered significant. Results: Compared with placebo, sitagliptin did not reduce CD4+ T cell count, plasma HIV RNA remained less than 48 copies/mL, RANTES and soluble TNF receptor II concentrations did not increase. SDF1α concentrations declined (P < .0002) in the sitagliptin group. The oral glucose tolerance levels improved in the sitagliptin group at week 8. Conclusions: Despite lowering SDF1α levels, sitagliptin did not adversely affect immune or virological status, or increase immune activation, but did improve glycemia in healthy, nondiabetic HIV-positive adults. These safety data

  13. Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

    PubMed

    Huang, Chi-Ping; Hsieh, Teng-Fu; Chen, Chi-Cheng; Hung, Xiao-Fan; Yu, Ai-Lin; Chang, Chawnshang; Shyr, Chih-Rong

    2014-09-26

    The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

  14. E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells.

    PubMed

    Aug, Argo; Altraja, Siiri; Kilk, Kalle; Porosk, Rando; Soomets, Ursel; Altraja, Alan

    2015-01-01

    E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC) and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL) on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC) with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1) to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1's maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

  15. 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

  16. When the serotonin transporter gene meets adversity: the contribution of animal models to understanding epigenetic mechanisms in affective disorders and resilience.

    PubMed

    Lesch, Klaus-Peter

    2011-01-01

    Although converging epidemiological evidence links exposure to stressful life events with increased risk for affective spectrum disorders, there is extraordinary interindividual variability in vulnerability to adversity. The environmentally moderated penetrance of genetic variation is thought to play a major role in determining who will either develop disease or remain resilient. Research on genetic factors in the aetiology of disorders of emotion regulation has, nevertheless, been complicated by a mysterious discrepancy between high heritability estimates and a scarcity of replicable gene-disorder associations. One explanation for this incongruity is that at least some specific gene effects are conditional on environmental cues, i.e. gene-by-environment interaction (G × E) is present. For example, a remarkable number of studies reported an association of variation in the human serotonin (5-HT) transporter gene (SLC6A4, 5-HTT, SERT) with emotional and cognitive traits as well as increased risk for depression in interaction with psychosocial adversity. The results from investigations in non-human primate and mouse support the occurrence of G × E interaction by showing that variation of 5-HTT function is associated with a vulnerability to adversity across the lifespan leading to unfavourable outcomes resembling various neuropsychiatric disorders. The neural and molecular mechanisms by which environmental adversity in early life increases disease risk in adulthood are not known but may include epigenetic programming of gene expression during development. Epigenetic mechanisms, such as DNA methylation and chromatin modification, are dynamic and reversible and may also provide targets for intervention strategies (see Bountra et al., Curr Top Behav Neurosci, 2011). Animal models amenable to genetic manipulation are useful in the identification of molecular mechanisms underlying epigenetic programming by adverse environments and individual differences in

  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. Child temperament, parent affect, and feeding in normal and overweight preschool children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite overwhelming evidence showing that parent emotional affect impacts parenting directives and child outcomes, little research has focused on the influence of parent affect on feeding as a mechanism in shaping children's eating patterns. Utilizing an instrument characterizing parent strategies ...

  19. Presenting Thin Media Models Affects Women's Choice of Diet or Normal Snacks

    ERIC Educational Resources Information Center

    Krahe, Barbara; Krause, Christina

    2010-01-01

    Our study explored the influence of thin- versus normal-size media models and of self-reported restrained eating behavior on women's observed snacking behavior. Fifty female undergraduates saw a set of advertisements for beauty products showing either thin or computer-altered normal-size female models, allegedly as part of a study on effective…

  20. Protein-enriched meal replacements do not adversely affect liver, kidney or bone density: an outpatient randomized controlled trial

    PubMed Central

    2010-01-01

    0.19 g/cm2, p = 0.210; SP -0.03 ± 0.17 g/cm2, p = 0.320) in either group over one year. Conclusions These studies demonstrate that protein-enriched meals replacements as compared to standard meal replacements recommended for weight management do not have adverse effects on routine measures of liver function, renal function or bone density at one year. Clinicaltrial.gov: NCT01030354. PMID:21194471

  1. Exposure to perfluorooctane sulfonic acid (PFOS) adversely affects the life-cycle of the damselfly Enallagma cyathigerum.

    PubMed

    Bots, Jessica; De Bruyn, Luc; Snijkers, Tom; Van den Branden, Bert; Van Gossum, Hans

    2010-03-01

    We evaluated whether life-time exposure to PFOS affects egg development, hatching, larval development, survival, metamorphosis and body mass of Enallagma cyathigerum (Insecta: Odonata). Eggs and larvae were exposed to five concentrations ranging from 0 to 10000 microg/L. Our results show reduced egg hatching success, slower larval development, greater larval mortality, and decreased metamorphosis success with increasing PFOS concentration. PFOS had no effect on egg developmental time and hatching or on mass of adults. Eggs were the least sensitive stage (NOEC=10000 microg/L). Larval NOEC values were 1000 times smaller (10 microg/L). Successful metamorphosis was the most sensitive response trait studied (NOEC<10 microg/L). The NOEC value suggests that E. cyathigerum is amongst the most sensitive freshwater organisms tested. NOEC for metamorphosis is less than 10-times greater than the ordinary reported environmental concentrations in freshwater, but is more than 200-times smaller than the greatest concentrations measured after accidental releases.

  2. Human Cytomegalovirus Infant Infection Adversely Affects Growth and Development in Maternally HIV-Exposed and Unexposed Infants in Zambia

    PubMed Central

    Larke, N.; Sanz-Ramos, M.; Bates, M.; Musonda, K.; Manno, D.; Siame, J.; Monze, M.; Filteau, S.

    2012-01-01

    Background. Human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) coinfections have been shown to increase infant morbidity, mortality, and AIDS progression. In HIV-endemic regions, maternal HIV-exposed but HIV-uninfected infants, which is the majority of children affected by HIV, also show poor growth and increased morbidity. Although nutrition has been examined, the effects of HCMV infection have not been evaluated. We studied the effects of HCMV infection on the growth, development, and health of maternally HIV-exposed and unexposed infants in Zambia. Methods. Infants were examined in a cohort recruited to a trial of micronutrient-fortified complementary foods. HIV-infected mothers and infants had received perinatal antiretroviral therapy to prevent mother-to-child HIV transmission. Growth, development, and morbidity were analyzed by linear regression analyses in relation to maternal HIV exposure and HCMV infection, as screened by sera DNA for viremia at 6 months of age and by antibody for infection at 18 months. Results. All HCMV-seropositive infants had decreased length-for-age by 18 months compared with seronegative infants (standard deviation [z]-score difference: −0.44 [95% confidence interval {CI}, −.72 to −.17]; P = .002). In HIV-exposed infants, those who were HCMV positive compared with those who were negative, also had reduced head size (mean z-score difference: −0.72 [95% CI, −1.23 to −.22]; P = .01) and lower psychomotor development (Bayley test score difference: −4.1 [95% CI, −7.8 to −.5]; P = .03). HIV-exposed, HCMV-viremic infants were more commonly referred for hospital treatment than HCMV-negative infants. The effects of HCMV were unaffected by micronutrient fortification. Conclusion. HCMV affects child growth, development, and morbidity of African infants, particularly in those maternally exposed to HIV. HCMV is therefore a risk factor for child health in this region. PMID:22247303

  3. Mutation increasing β-carotene concentrations does not adversely affect concentrations of essential mineral elements in pepper fruit

    PubMed Central

    Thompson, Jacqueline A.; Penchev, Emil A.; Nielen, Stephan

    2017-01-01

    Vitamin and mineral deficiencies are prevalent in human populations throughout the world. Vitamin A deficiency affects hundreds of millions of pre-school age children in low income countries. Fruits of pepper (Capsicum annuum L.) can be a major dietary source of precursors to Vitamin A biosynthesis, such as β-carotene. Recently, pepper breeding programs have introduced the orange-fruited (of) trait of the mutant variety Oranzheva kapiya, which is associated with high fruit β-carotene concentrations, to the mutant variety Albena. In this manuscript, concentrations of β-carotene and mineral elements (magnesium, phosphorus, sulphur, potassium, zinc, calcium, manganese, iron and copper) were compared in fruit from P31, a red-fruited genotype derived from the variety Albena, and M38, a genotype developed by transferring the orange-fruited mutation (of) into Albena. It was observed that fruit from M38 plants had greater β-carotene concentration at both commercial and botanical maturity (4.9 and 52.7 mg / kg fresh weight, respectively) than fruit from P31 plants (2.3 and 30.1 mg / kg fresh weight, respectively). The mutation producing high β-carotene concentrations in pepper fruits had no detrimental effect on the concentrations of mineral elements required for human nutrition. PMID:28207797

  4. Mutation increasing β-carotene concentrations does not adversely affect concentrations of essential mineral elements in pepper fruit.

    PubMed

    Tomlekova, Nasya B; White, Philip J; Thompson, Jacqueline A; Penchev, Emil A; Nielen, Stephan

    2017-01-01

    Vitamin and mineral deficiencies are prevalent in human populations throughout the world. Vitamin A deficiency affects hundreds of millions of pre-school age children in low income countries. Fruits of pepper (Capsicum annuum L.) can be a major dietary source of precursors to Vitamin A biosynthesis, such as β-carotene. Recently, pepper breeding programs have introduced the orange-fruited (of) trait of the mutant variety Oranzheva kapiya, which is associated with high fruit β-carotene concentrations, to the mutant variety Albena. In this manuscript, concentrations of β-carotene and mineral elements (magnesium, phosphorus, sulphur, potassium, zinc, calcium, manganese, iron and copper) were compared in fruit from P31, a red-fruited genotype derived from the variety Albena, and M38, a genotype developed by transferring the orange-fruited mutation (of) into Albena. It was observed that fruit from M38 plants had greater β-carotene concentration at both commercial and botanical maturity (4.9 and 52.7 mg / kg fresh weight, respectively) than fruit from P31 plants (2.3 and 30.1 mg / kg fresh weight, respectively). The mutation producing high β-carotene concentrations in pepper fruits had no detrimental effect on the concentrations of mineral elements required for human nutrition.

  5. Unbalanced international collaboration affects adversely the usefulness of countries' scientific output as well as their technological and social impact.

    PubMed

    Zanotto, Sonia R; Haeffner, Cristina; Guimarães, Jorge A

    2016-01-01

    The unbalanced international scientific collaboration as cause of misleading information on the country's contribution to the scientific world output was analyzed. ESI Data Base (Thomson Reuters' InCites), covering the scientific production of 217 active countries in the period 2010-2014 was used. International collaboration implicates in a high percentage (33.1 %) of double-counted world articles, thus impacting qualitative data as citations, impact and impact relative to word. The countries were divided into three groups, according to their individual contribution to the world publications: Group I (24 countries, at least 1 %) representing 83.9 % of the total double-counted world articles. Group II (40 countries, 0.1-0.99 % each). Group III, 153 countries (70.5 %) with <0.1 % and altogether 1.9 % of the world. Qualitative characteristics of each group were also analyzed: percentage of the country's GNP applied in R&D, proportion of Scientists and Engineers per million inhabitants and Human Development Index. Average international collaboration were: Group I, 43.0 %; Group II, 55.8 % and Group III, 85.2 %. We concluded that very high and unbalanced international collaboration, as presented by many countries, misrepresent the importance of their scientific production, technological and social outputs. Furthermore, it jeopardizes qualitative outputs of the countries themselves, artificially increasing their scientific impact, affecting all fields and therefore, the whole world. The data confirm that when dealing with the qualitative contribution of countries, it is necessary to take in consideration the level of international cooperation because, as seen here, it can and in fact it does create false impression of the real contribution of countries.

  6. Factors Affecting the Normalization of CALL in Chinese Senior High Schools

    ERIC Educational Resources Information Center

    He, Bi; Puakpong, Nattaya; Lian, Andrew

    2015-01-01

    With the development of Information Technology, increasing attention has been paid to Computer Assisted Language Learning (CALL). Meanwhile, increasing enthusiasm is seen for English learning and teaching in China. Yet, few research studies have focused on the normalization of CALL in ethnically diverse areas. In response to this research gap,…

  7. Polyphenol oxidase affects normal nodule development in red clover (Trifolium pratense L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyphenol oxidase (PPO) may have multiple functions in tissues, depending on its cellular or tissue localization. We used PPO RNAi transformants of red clover (Trifolium pratense) to determine the role PPO plays in normal development of plants, and especially in nitrogen-fixing nodules. In red clov...

  8. Single layer centrifugation of stallion spermatozoa through Androcoll™-E does not adversely affect their capacitation-like status, as measured by CTC staining.

    PubMed

    Bergqvist, A-S; Johannisson, A; Bäckgren, L; Dalin, A-M; Rodriguez-Martinez, H; Morrell, J M

    2011-02-01

    This study was designed to evaluate the effect of single layer centrifugation (SLC) and subsequent cold storage on stallion sperm capacitation-like status and acrosome reaction. Three stallions were included in the study, with three ejaculates per stallion. The samples were examined 4, 24 and 72 h after collection, extension and SLC, with storage at 6°C. Sperm capacitation-like status was investigated using the fluorescent dye chlortetracycline (CTC). There was no difference in capacitation-like status between colloid-selected and non-selected spermatozoa. Sperm motility decreased significantly during cold storage, whereas the proportion of apparently capacitated spermatozoa increased. There was no change in the proportion of acrosome-reacted spermatozoa. In conclusion, SLC through Androcoll™-E does not adversely affect the capacitation-like status of stallion spermatozoa, although it did increase with time during cold storage.

  9. Linear and nonlinear analysis of normal and CAD-affected heart rate signals.

    PubMed

    Acharya, U Rajendra; Faust, Oliver; Sree, Vinitha; Swapna, G; Martis, Roshan Joy; Kadri, Nahrizul Adib; Suri, Jasjit S

    2014-01-01

    Coronary artery disease (CAD) is one of the dangerous cardiac disease, often may lead to sudden cardiac death. It is difficult to diagnose CAD by manual inspection of electrocardiogram (ECG) signals. To automate this detection task, in this study, we extracted the heart rate (HR) from the ECG signals and used them as base signal for further analysis. We then analyzed the HR signals of both normal and CAD subjects using (i) time domain, (ii) frequency domain and (iii) nonlinear techniques. The following are the nonlinear methods that were used in this work: Poincare plots, Recurrence Quantification Analysis (RQA) parameters, Shannon entropy, Approximate Entropy (ApEn), Sample Entropy (SampEn), Higher Order Spectra (HOS) methods, Detrended Fluctuation Analysis (DFA), Empirical Mode Decomposition (EMD), Cumulants, and Correlation Dimension. As a result of the analysis, we present unique recurrence, Poincare and HOS plots for normal and CAD subjects. We have also observed significant variations in the range of these features with respect to normal and CAD classes, and have presented the same in this paper. We found that the RQA parameters were higher for CAD subjects indicating more rhythm. Since the activity of CAD subjects is less, similar signal patterns repeat more frequently compared to the normal subjects. The entropy based parameters, ApEn and SampEn, are lower for CAD subjects indicating lower entropy (less activity due to impairment) for CAD. Almost all HOS parameters showed higher values for the CAD group, indicating the presence of higher frequency content in the CAD signals. Thus, our study provides a deep insight into how such nonlinear features could be exploited to effectively and reliably detect the presence of CAD.

  10. Relationship between Defenses, Personality, and Affect during a Stress Task in Normal Adolescents

    ERIC Educational Resources Information Center

    Steiner, Hans; Erickson, Sarah J.; MacLean, Peggy; Medic, Sanja; Plattner, Belinda; Koopman, Cheryl

    2007-01-01

    Objective: Although there are extensive data on the relationship between personality and stress reactivity in adults, there is little comparable empirical research with adolescents. This study examines the simultaneous relationships between long term functioning (personality, defenses) and observed stress reactivity (affect) in adolescents.…

  11. Mapping patterns of depression-related brain regions with cytochrome oxidase histochemistry: relevance of animal affective systems to human disorders, with a focus on resilience to adverse events.

    PubMed

    Harro, Jaanus; Kanarik, Margus; Matrov, Denis; Panksepp, Jaak

    2011-10-01

    The search for novel antidepressants may be facilitated by pre-clinical animal models that relay on specific neural circuit and related neurochemical endpoint measures, which are anchored in concrete neuro-anatomical and functional neural-network analyzes. One of the most important initial considerations must be which regions of the brain are candidates for the maladaptive response to depressogenic challenges. Consideration of persistent differences or changes in the activity of cerebral networks can be achieved by mapping oxidative metabolism in ethologically or pathogenetically relevant animal models. Cytochrome oxidase histochemistry is a technique suitable to detect regional long-term brain activity changes relative to control conditions and has been used in a variety of animal models. This work is summarized and indicates that major changes occur mainly in subcortical areas, highlighting specific brain regions where some alterations in regional oxidative metabolism may represent adaptive changes to depressogenic adverse life events, while others may reflect failures of adaptation. Many of these changes in oxidative metabolism may depend upon the integrity of serotonergic neurotransmission, and occur in several brain regions shown by other techniques to be involved in endogenous affective circuits that control emotional behaviors as well as related higher brain regions that integrate learning and cognitive information processing. These brain regions appear as primary targets for further identification of endophenotypes specific to affective disorders.

  12. Reelin Proteolysis Affects Signaling Related to Normal Synapse Function and Neurodegeneration

    PubMed Central

    Lussier, April L.; Weeber, Edwin J.; Rebeck, G. William

    2016-01-01

    Reelin is a neurodevelopmental protein important in adult synaptic plasticity and learning and memory. Recent evidence points to the importance for Reelin proteolysis in normal signaling and in cognitive function. Support for the dysfunction of Reelin proteolysis in neurodegeneration and cognitive dysfunction comes from postmortem analysis of Alzheimer’s diseases (AD) tissues including cerebral spinal fluid (CSF), showing that levels of Reelin fragments are altered in AD compared to control. Potential key proteases involved in Reelin proteolysis have recently been defined, identifying processes that could be altered in neurodegeneration. Introduction of full-length Reelin and its proteolytic fragments into several mouse models of neurodegeneration and neuropsychiatric disorders quickly promote learning and memory. These findings support a role for Reelin in learning and memory and suggest further understanding of these processes are important to harness the potential of this pathway in treating cognitive symptoms in neuropsychiatric and neurodegenerative diseases. PMID:27065802

  13. Evaluation of normalized energy recovery (NER) in microbial fuel cells affected by reactor dimensions and substrates.

    PubMed

    Xiao, Li; Ge, Zheng; Kelly, Patrick; Zhang, Fei; He, Zhen

    2014-04-01

    The objective of this study is to provide an initial evaluation of normalized energy recovery (NER - a new parameter for presenting energy performance) in microbial fuel cells (MFCs) through investigation of the effects of reactor dimensions and anode substrates. Although the larger-size MFCs generally have lower maximum power densities, their maximum NER is comparable to that of the smaller MFCs at the same anolyte flow rate. The mixed messages obtained from the MFC size tests suggest that MFCs can be further scaled up without decreasing energy recovery under certain conditions. The low-strength substrates seem to be more suitable for MFC treatment of wastewater, in terms of both energy recovery and organic removal. However, because the MFCs could not achieve the maximum NER and the maximum organic removal efficiency at the same time, one must determine a major goal for MFCs treating wastewater between energy recovery and contaminant removal.

  14. Neither cimetidine nor probenecid affect the pharmacokinetics of tenoxicam in normal volunteers.

    PubMed Central

    Day, R O; Geisslinger, G; Paull, P; Williams, K M

    1994-01-01

    The effect of pretreatment with cimetidine (1 g day-1, 7 days) and of probenecid (1 g twice daily, 4 days) on the pharmacokinetics of tenoxicam (single oral dose, 20 mg) was studied in six healthy volunteers. Cmax was increased significantly when tenoxicam was given with probenecid (2.8 micrograms ml-1 alone, 3.5 micrograms ml-1 after probenecid; P < 0.005). No other pharmacokinetic parameters were altered significantly by either drug. It is concluded that neither cimetidine nor probenecid affects the pharmacokinetics of tenoxicam in a clinically important way. PMID:8148224

  15. Polyphenol oxidase affects normal nodule development in red clover (Trifolium pratense L.)

    PubMed Central

    Webb, K. Judith; Cookson, Alan; Allison, Gordon; Sullivan, Michael L.; Winters, Ana L.

    2014-01-01

    Polyphenol oxidase (PPO) may have multiple functions in tissues depending on its cellular or tissue localization. Here we use PPO RNAi transformants of red clover (Trifolium pratense) to determine the role PPO plays in normal development of plants, and especially in N2-fixing nodules. In red clover, PPO was not essential for either growth or nodule production, or for nodule function in plants grown under optimal, N-free conditions. However, absence of PPO resulted in a more reduced environment in all tissues, as measured by redox potential, and caused subtle developmental changes in nodules. Leaves and, to a lesser extent nodules, lacking PPO tended to accumulate phenolic compounds. A comparison of nodules of two representative contrasting clones by microscopy revealed that nodules lacking PPO were morphologically and anatomically subtly altered, and that phenolics accumulated in different cells and tissues. Developing nodules lacking PPO were longer, and there were more cell layers within the squashed cell layer (SCL), but the walls of these cells were less thickened and the cells were less squashed. Within the N2-fixing zone, bacteroids appeared more granular and were less tightly packed together, and were similar to developmentally compromised bacteroids elicited by catalase mutant rhizobia reported elsewhere. PMID:25566275

  16. Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

    NASA Technical Reports Server (NTRS)

    Glenny, R. W.; Robertson, H. T.; Hlastala, M. P.

    2000-01-01

    To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

  17. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.

    PubMed

    Sharman, Matthew J; Kraemer, William J; Love, Dawn M; Avery, Neva G; Gómez, Ana L; Scheett, Timothy P; Volek, Jeff S

    2002-07-01

    Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.

  18. PMCA activity and membrane tubulin affect deformability of erythrocytes from normal and hypertensive human subjects.

    PubMed

    Monesterolo, Noelia E; Nigra, Ayelen D; Campetelli, Alexis N; Santander, Verónica S; Rivelli, Juan F; Arce, Carlos A; Casale, Cesar H

    2015-11-01

    Our previous studies demonstrated formation of a complex between acetylated tubulin and brain plasma membrane Ca(2+)-ATPase (PMCA), and the effect of the lipid environment on structure of this complex and on PMCA activity. Deformability of erythrocytes from hypertensive human subjects was reduced by an increase in membrane tubulin content. In the present study, we examined the regulation of PMCA activity by tubulin in normotensive and hypertensive erythrocytes, and the effect of exogenously added diacylglycerol (DAG) and phosphatidic acid (PA) on erythrocyte deformability. Some of the key findings were that: (i) PMCA was associated with tubulin in normotensive and hypertensive erythrocytes, (ii) PMCA enzyme activity was directly correlated with erythrocyte deformability, and (iii) when tubulin was present in the erythrocyte membrane, treatment with DAG or PA led to increased deformability and associated PMCA activity. Taken together, our findings indicate that PMCA activity is involved in deformability of both normotensive and hypertensive erythrocytes. This rheological property of erythrocytes is affected by acetylated tubulin and its lipid environment because both regulate PMCA activity.

  19. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues.

    PubMed

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-02-09

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.

  20. Down-regulation of muscarinic acetylcholine receptor M2 adversely affects the expression of Alzheimer's disease-relevant genes and proteins.

    PubMed

    Zuchner, Thole; Schliebs, Reinhard; Perez-Polo, J Regino

    2005-10-01

    Beta-amyloid peptides play a major role in the pathogenesis of Alzheimer's disease (AD). Therefore, preventing beta-amyloid formation by inhibition of the beta site amyloid precursor protein-cleaving enzyme (BACE) 1 is considered as a potential strategy to treat AD. Cholinergic mechanisms have been shown to control amyloid precursor protein processing and the number of muscarinic M2-acetylcholine receptors is decreased in brain regions of patients with AD enriched with senile plaques. Therefore, the present study investigates the effect of this M2 muscarinic receptor down-regulation by siRNA on total gene expression and on regulation of BACE1 in particular in SK-SH-SY5Y cells. This model system was used for microarray analysis after carbachol stimulation of siRNA-treated cells compared with carbachol stimulated, non-siRNA-treated cells. The same model system was used to elucidate changes at the protein level by using two-dimensional gels followed by Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) analysis. Taken together, the results indicate that the M2 acetylcholine receptor down-regulation in brains of patients with AD has important effects on the expression of several genes and proteins with major functions in the pathology of AD. This includes beta-secretase BACE1 as well as several modulators of the tau protein and other AD-relevant genes and proteins. Moreover, most of these genes and proteins are adversely affected against the background of AD.

  1. Maternal fish oil supplementation during lactation may adversely affect long-term blood pressure, energy intake, and physical activity of 7-year-old boys.

    PubMed

    Asserhøj, Marie; Nehammer, Sofie; Matthiessen, Jeppe; Michaelsen, Kim F; Lauritzen, Lotte

    2009-02-01

    Early nutrition may program obesity and cardiovascular risk later in life, and one of the potential agents is (n-3) long-chain PUFA (LCPUFA). In this study, our objective was to examine whether fish oil (FO) supplementation during lactation affects blood pressure and body composition of children. Danish mothers (n = 122) were randomized to FO [1.5 g/d (n-3) LCPUFA] or olive oil (OO) supplementations during the first 4 mo of lactation. The trial also included a high-fish intake reference group (n = 53). Ninety-eight children were followed-up with blood pressure and anthropometry measurements at 7 y. Diet and physical activity level (PAL) were assessed by 4-d weighed dietary records and ActiReg. The PAL value was 4% lower (P = 0.048) and energy intake (EI) of the boys was 1.1 +/- 0.4 MJ/d higher (P = 0.014) in the FO group than in the OO group. Starch intake was 15 +/- 6 g/d higher (P = 0.012) in the FO group, but there were no other differences in diet. Body composition did not differ between the randomized groups with or without adjustment for starch intake, EI, and PAL. FO boys had 6 mm Hg higher diastolic and mean arterial blood pressure than OO boys (P < 0.01), but girls did not differ. Within the randomized groups, blood pressure was not correlated with maternal RBC (n-3) LCPUFA after the intervention, but PAL values were (r = -0.277; P = 0.038). We previously found higher BMI at 2.5 y in the FO group, but the difference did not persist. The differences in blood pressure, EI, and PAL, particularly among boys, suggest that early (n-3) LCPUFA intake may have adverse effects, which should be investigated in future studies.

  2. DELAY OF 2 OR 6 WEEKS ADVERSELY AFFECTS THE FUNCTIONAL OUTCOME OF AUGMENTED PRIMARY REPAIR OF THE PORCINE ANTERIOR CRUCIATE LIGAMENT

    PubMed Central

    Magarian, Elise M.; Fleming, Braden C.; Harrison, Sophia L.; Mastrangelo, Ashley N.; Badger, Gary J.; Murray, Martha M.

    2010-01-01

    BACKGROUND Enhanced primary ACL repair, in which suture repair is performed in conjunction with a collagen-platelet composite to stimulate healing, is a potential new treatment option for ACL injuries. Previous studies have evaluated this approach at the time of ACL disruption. HYPOTHESIS In this study, we hypothesized that delaying surgery by 2 or 6 weeks would have a significant effect on the functional outcome of the repair. STUDY DESIGN Controlled Laboratory Study METHODS Sixteen female Yorkshire pigs underwent staged, bilateral surgical ACL transections. ACL transection was initially performed on one knee and the knee closed. Two or six weeks later, enhanced primary repair was performed in that knee while the contralateral knee had an ACL transection and immediate repair. Biomechanical parameters were measured after 15 weeks in vivo to determine the effect of delay time relative to immediate repair on the healing response. RESULTS Yield load of the repairs at 15 weeks was decreased by 40% and 60% in the groups where repair was delayed for 2 and 6 weeks respectively (p=0.01). Maximum load showed similar results (55% and 60% decrease in the 2 and 6 week delay groups respectively, p=0.011). Linear stiffness also was adversely affected by delay (50% decrease compared to immediate repair after either a 2 or 6 week delay, p=0.011). AP laxity after 15 weeks of healing was 40% higher in knees repaired after a 2 week delay, and 10% higher in those repaired after a six week delay (p=0.012) when tested at 30 degrees of flexion, but was not significantly affected by delay when tested at 60 or 90 degrees (p=0.21). CONCLUSIONS A delay between ACL injury and enhanced primary repair has a significant negative effect on the functional performance of the repair. CLINICAL RELEVANCE As future investigations assess new techniques of ACL repair, the timing of the repair should be considered in the design and the interpretation of experimental studies. PMID:20855556

  3. Is detection of adverse events affected by record review methodology? an evaluation of the “Harvard Medical Practice Study” method and the “Global Trigger Tool”

    PubMed Central

    2013-01-01

    Background There has been a theoretical debate as to which retrospective record review method is the most valid, reliable, cost efficient and feasible for detecting adverse events. The aim of the present study was to evaluate the feasibility and capability of two common retrospective record review methods, the “Harvard Medical Practice Study” method and the “Global Trigger Tool” in detecting adverse events in adult orthopaedic inpatients. Methods We performed a three-stage structured retrospective record review process in a random sample of 350 orthopaedic admissions during 2009 at a Swedish university hospital. Two teams comprised each of a registered nurse and two physicians were assigned, one to each method. All records were primarily reviewed by registered nurses. Records containing a potential adverse event were forwarded to physicians for review in stage 2. Physicians made an independent review regarding, for example, healthcare causation, preventability and severity. In the third review stage all adverse events that were found with the two methods together were compared and all discrepancies after review stage 2 were analysed. Events that had not been identified by one of the methods in the first two review stages were reviewed by the respective physicians. Results Altogether, 160 different adverse events were identified in 105 (30.0%) of the 350 records with both methods combined. The “Harvard Medical Practice Study” method identified 155 of the 160 (96.9%, 95% CI: 92.9-99.0) adverse events in 104 (29.7%) records compared with 137 (85.6%, 95% CI: 79.2-90.7) adverse events in 98 (28.0%) records using the “Global Trigger Tool”. Adverse events “causing harm without permanent disability” accounted for most of the observed difference. The overall positive predictive value for criteria and triggers using the “Harvard Medical Practice Study” method and the “Global Trigger Tool” was 40.3% and 30.4%, respectively. Conclusions More adverse

  4. Factors Affecting Adverse Drug Reaction Reporting of Healthcare Professionals and Their Knowledge, Attitude, and Practice towards ADR Reporting in Nekemte Town, West Ethiopia

    PubMed Central

    Gurmesa, Lense Temesgen

    2016-01-01

    Background. Adverse drug reactions are global problems of major concern. Adverse drug reaction reporting helps the drug monitoring system to detect the unwanted effects of those drugs which are already in the market. Aims. To assess the knowledge, attitude, and practice of health care professionals working in Nekemte town towards adverse drug reaction reporting. Methods and Materials. A cross-sectional study design was conducted on a total of 133 health care professionals by interview to assess their knowledge, attitude, and practice using structured questionnaire. Results. Of the total respondents, only 64 (48.2%), 56 (42.1%), and 13 (9.8%) health care professionals have correctly answered the knowledge, attitude, and practice assessment questions, respectively. Lack of awareness and knowledge on what, when, and to whom to report adverse drug reactions and lack of commitments of health care professionals were identified as the major discouraging factors against adverse drug reaction reporting. Conclusion. This study has revealed that the knowledge, attitude, and practice of the health care professionals working in Nekemte town towards spontaneous adverse drug reaction reporting were low that we would like to recommend the concerned bodies to strive on the improvement of the knowledge, attitude, and practice status of health care professionals. PMID:28042569

  5. Length of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause

    PubMed Central

    Ruth, Katherine S.; Bennett, Claire E.; Schoemaker, Minouk J.; Weedon, Michael N.; Swerdlow, Anthony J.; Murray, Anna

    2016-01-01

    STUDY QUESTION Is the length of FMR1 repeat alleles within the normal range associated with the risk of early menopause? SUMMARY ANSWER The length of repeat alleles within the normal range does not substantially affect risk of early menopause. WHAT IS KNOWN ALREADY There is a strong, well-established relationship between length of premutation FMR1 alleles and age at menopause, suggesting that this relationship could continue into the normal range. Within the normal range, there is conflicting evidence; differences in ovarian reserve have been identified with FMR1 repeat allele length, but a recent population-based study did not find any association with age at menopause as a quantitative trait. STUDY DESIGN, SIZE, DURATION We analysed cross-sectional baseline survey data collected at recruitment from 2004 to 2010 from a population-based, prospective epidemiological cohort study of >110 000 women to investigate whether repeat allele length was associated with early menopause. PARTICIPANTS/MATERIALS, SETTING, METHOD We included 4333 women from the Breakthrough Generations Study (BGS), of whom 2118 were early menopause cases (menopause under 46 years) and 2215 were controls. We analysed the relationship between length of FMR1 alleles and early menopause using logistic regression with allele length as continuous and categorical variables. We also conducted analyses with the outcome age at menopause as a quantitative trait as well as appropriate sensitivity and exploratory analyses. MAIN RESULTS AND THE ROLE OF CHANCE There was no association of the shorter or longer FMR1 allele or their combined genotype with the clinically relevant end point of early menopause in our main analysis. Likewise, there were no associations with age at menopause as a quantitative trait in our secondary analysis. LIMITATIONS, REASONS FOR CAUTION Women with homozygous alleles in the normal range may have undetected FMR1 premutation alleles, although there was no evidence to suggest this. We

  6. 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 ...

  7. Gender, Race, and Diet Affect Platelet Function Tests in Normal Subjects Contributing to a High Rate of Abnormal Results

    PubMed Central

    Miller, Connie H.; Rice, Anne S.; Garrett, Katherine; Stein, Sidney F.

    2015-01-01

    Summary To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2–6 occasions at 2 week intervals using 4 methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in whole blood (WB) in the CL and Multiplate Platelet Function Analyzer (MP), with ATP release (REL) in CL-PRP and CL-WB. Food and medication exposures were recorded prospectively for 2 weeks prior to each blood draw. At least one AGG abnormality was seen in 21% of 81 drug-free specimens with CL-PRP, 15% with CL-WB, 13% with BD-PRP, and 6% with MP-WB, increasing with inclusion of REL to 28% for CL-PRP and 30% for CL-WB. Epinephrine AGG and REL were significantly reduced in males (P<0.0001). Ristocetin AGG and collagen and thrombin REL were significantly reduced in Blacks (P<0.0001). One-third of specimens drawn following flavonoid-rich food exposures had aberrant results, compared to 8.5% of specimens without such exposures (P=0.0035). PRP tests had less intra-individual variation than WB tests. Gender, race, diet, and test system affected results of platelet function testing in healthy subjects, suggesting caution when interpreting the results of platelet function testing in patients. PMID:24617520

  8. Effects of simplified ethanol-wet bonding technique on immediate bond strength with normal versus caries-affected dentin

    PubMed Central

    Aggarwal, Vivek; Singla, Mamta; Sharma, Ritu; Miglani, Sanjay; Bhasin, Saranjit Singh

    2016-01-01

    Aim: The aim of the present study was to evaluate whether the use of simplified ethanol-wet bonding (EWB) technique improved the immediate microtensile bond strength (μTBS) between resin composite and caries-affected dentin (CAD). Materials and Methods: Twenty-four extracted carious human permanent molars were sectioned to expose the carious lesion. The carious dentin was excavated until CAD was exposed. The samples were divided into two groups: water-wet bonding with Adper Scotchbond Multi-Purpose and a simplified EWB (three 100% ethanol applications for 30 s each), followed by application of an experimental hydrophobic primer and restoration. The samples were vertically sectioned to produce 1 mm × 1 mm thick slabs. The normal dentin (ND) slabs and CAD slabs were identified and were subjected to μTBS evaluation. Slabs from four teeth (two from each group) were evaluated under microscope. Data were analyzed using two-way ANOVA and post hoc Holm–Sidak test at P < 0.05. Results: EWB improved the μTBS in ND but not in CAD group. The dentinal tubules in CAD group showed sclerotic activity with minimal or no hybrid layer. Conclusions: Simplified ethanol bonding does not improve the bond strength in CAD. PMID:27656059

  9. Minor serous and clear cell components adversely affect prognosis in ''mixed-type'' endometrial carcinomas: a clinicopathologic study of 36 stage-I cases.

    PubMed

    Quddus, M Ruhul; Sung, C James; Zhang, Cunxian; Lawrence, W Dwayne

    2010-07-01

    Most endometrial carcinomas contain only 1 Müllerian cell type although the presence of 2 or more cell types within 1 tumor, for example a predominantly low-grade endometrioid carcinoma with a minor component (arbitrarily defined as 30% or less) of high-grade serous and/or clear cell carcinoma, is not uncommon. The current study attempts to evaluate whether the presence of minor serous or clear cell components exerts an adverse effect on the prognosis in stage-I endometrial carcinomas of ''mixed-type.'' The study cases include 22 cases of stage-I endometrioid carcinoma with a minor component of serous carcinoma and 14 cases of endometrioid carcinoma with a minor component of clear cell carcinoma. Minor components were arbitrarily defined as representing anywhere between 5% and 30% of the total tumor. The study cases were compared with 56 cases of histologically pure age-matched and stage-matched endometrioid carcinomas, 6 pure serous carcinomas, and 13 pure clear cell carcinomas. All study and control cases were fully staged. Treatment history and outcome status were obtained and follow-up ranged from 56 to 140 months. Our study suggests that the presence of minor components of serous and clear cell carcinoma, defined as between 5% and 30%, within a mixed-type endometrial carcinoma appears to adversely influence the long-term survival of stage-I tumors, although a larger study is needed to corroborate our findings.

  10. 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

  11. 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

    2015-04-07

    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.

  12. 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

  13. 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

    2014-06-03

    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.

  14. 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.

  15. Viscoelastic properties of normal and cancerous human breast cells are affected differently by contact to adjacent cells.

    PubMed

    Schierbaum, Nicolas; Rheinlaender, Johannes; Schäffer, Tilman E

    2017-04-07

    Malignant transformation drastically alters the mechanical properties of the cell and its response to the surrounding cellular environment. We studied the influence of the physical contact between adjacent cells in an epithelial monolayer on the viscoelastic behavior of normal MCF10A, non-invasive cancerous MCF7, and invasive cancerous MDA-MB-231 human breast cells. Using an atomic force microscopy (AFM) imaging technique termed force clamp force mapping (FCFM) to record images of the viscoelastic material properties of sparse and confluent cells, we found that normal MCF10A cells are stiffer and have a lower fluidity when at confluent than at sparse density. Contrarily, cancerous MCF7 and MDA-MB-231 cells do not stiffen and do not decrease their fluidity when progressing from sparse to confluent density. The behavior of normal MCF10A cells appears to be governed by the formation of stable cell-cell contacts, because their disruption with a calcium-chelator (EGTA) causes the stiffness and fluidity values to return to those at sparse density. In contrast, EGTA-treatment of MCF7 and MDA-MB-231 cells does not change their viscoelastic properties. Confocal fluorescence microscopy showed that the change of the viscoelastic behavior in MCF10A cells when going from sparse to confluent density is accompanied by a remodeling of the actin cytoskeleton into thick stress fiber bundles, while in MCF7 and MDA-MB-231 cells the actin cytoskeleton is only composed of thin and short fibers, regardless of cell density. While the observed behavior of normal MCF10A cells might be crucial for providing mechanical stability and thus in turn integrity of the epithelial monolayer, the dysregulation of this behavior in cancerous MCF7 and MDA-MB-231 cells is possibly a central aspect of cancer progression in the epithelium.

  16. Temperature rise under normal and caries-affected primary tooth dentin disks during polymerization of adhesives and resin-containing dental materials.

    PubMed

    Tosun, Gul; Usumez, Aslihan; Yondem, Isa; Sener, Yagmur

    2008-05-01

    The purpose of this study was to compare the temperature rise under normal and caries-affected primary tooth dentin during photopolymerization of two adhesives and resin-containing restorative materials. Caries-affected and normal dentin disks were prepared from extracted primary molars with only mesial or distal approximal caries (4 mm in diameter, 1 mm in height). Temperature rise during photopolymerization of adhesive materials was measured with a J-type thermocouple wire that was connected to a data logger. Data were analyzed with two-way ANOVA and independent samples t-test. Temperature rise under caries-affected primary tooth dentin disks was higher than that of normal primary tooth dentin disks during polymerization of both adhesive systems and resin-containing dental materials (p < 0.05). It was found that adhesive systems induced a higher temperature rise during polymerization as compared to the resin-containing restorative materials (p < 0.05). In particular, temperature rise during polymerization of adhesive materials exceeded 5.5 degrees C under caries-affected primary tooth dentin.

  17. Maternal Food Restriction during Pregnancy and Lactation Adversely Affect Hepatic Growth and Lipid Metabolism in Three-Week-Old Rat Offspring

    PubMed Central

    Lee, Sangmi; You, Young-Ah; Kwon, Eun Jin; Jung, Sung-Chul; Jo, Inho; Kim, Young Ju

    2016-01-01

    Maternal malnutrition influences the early development of foetal adaptive changes for survival. We explored the effects of maternal undernutrition during gestation and lactation on hepatic growth and function. Sprague-Dawley rats were fed a normal or a food-restricted (FR) diet during gestation and/or lactation. We performed analyses of covariance (adjusting for the liver weight/body weight ratio) to compare hepatic growth and lipid metabolism among the offspring. Maternal FR during gestation triggered the development of wide spaces between hepatic cells and increased the expression of mammalian target of rapamycin (mTOR) in three-week-old male offspring compared with controls (both p < 0.05). Offspring nursed by FR dams exhibited wider spaces between hepatic cells and a lower liver weight/body weight ratio than control offspring, and increased mTOR expression (p < 0.05). Interestingly, the significant decrease in expression of lipogenic-related genes was dependent on carbohydrate-responsive element-binding protein, despite the increased expression of sterol regulatory element-binding protein 1 (SREBP1) (p < 0.05). This study demonstrated increased expression of key metabolic regulators (mTOR and SREBP1), alterations in lipid metabolism, and deficits in hepatic growth in the offspring of FR-treated dams. PMID:27983688

  18. Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis.

    PubMed

    van der Doelen, R H A; Deschamps, W; D'Annibale, C; Peeters, D; Wevers, R A; Zelena, D; Homberg, J R; Kozicz, T

    2014-07-08

    The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). Furthermore, 5-HTTLPR has been associated with abnormal functioning of the stress-responsive hypothalamo-pituitary-adrenal (HPA) axis. Here, we examined if, and at what level, the HPA-axis is affected in an animal model for ELS × 5-HTTLPR interactions. Heterozygous and homozygous 5-HTT knockout rats and their wild-type littermates were exposed daily at postnatal days 2-14 to 3 h of maternal separation. When grown to adulthood, plasma levels of adrenocorticotropic hormone (ACTH), and the major rat glucocorticoid, corticosterone (CORT), were measured. Furthermore, the gene expression of key HPA-axis players at the level of the hypothalamus, pituitary and adrenal glands was assessed. No 5-HTT genotype × ELS interaction effects on gene expression were observed at the level of the hypothalamus or pituitary. However, we found significant 5-HTT genotype × ELS interaction effects for plasma CORT levels and adrenal mRNA levels of the ACTH receptor, such that 5-HTT deficiency was associated under control conditions with increased, but after ELS with decreased basal HPA-axis activity. With the use of an in vitro adrenal assay, naïve 5-HTT knockout rats were furthermore shown to display increased adrenal ACTH sensitivity. Therefore, we conclude that basal HPA-axis activity is affected by the interaction of 5-HTT genotype and ELS, and is programmed, within the axis itself, predominantly at the level of the adrenal gland. This study therefore emphasizes the importance of the adrenal gland for HPA-related psychiatric disorders.

  19. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain.

    PubMed

    van der Doelen, Rick H A; Arnoldussen, Ilse A; Ghareh, Hussein; van Och, Liselot; Homberg, Judith R; Kozicz, Tamás

    2015-02-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene × Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid release upon exposure to stress. Both endophenotypes are regulated by the neuropeptide corticotropin-releasing factor (CRF) or hormone, which is expressed by the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central amygdala (CeA). Therefore, we hypothesized that altered regulation of the expression of CRF in these areas represents a major neurobiological mechanism underlying the interaction of early life stress and 5-HTT gene variation. The programming of gene transcription by Gene × Environment interactions has been proposed to involve epigenetic mechanisms such as DNA methylation. In this study, we report that early life stress and 5-HTT genotype interact to affect DNA methylation of the Crf gene promoter in the CeA of adult male rats. Furthermore, we found that DNA methylation of a specific site in the Crf promoter significantly correlated with CRF mRNA levels in the CeA. Moreover, CeA CRF mRNA levels correlated with stress coping behavior in a learned helplessness paradigm. Together, our findings warrant further investigation of the link of Crf promoter methylation and CRF expression in the CeA with behavioral changes that are relevant for psychopathology.

  20. 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.

  1. Estradiol differently affects melanin synthesis of malignant and normal melanocytes: a relationship with clock and clock-controlled genes.

    PubMed

    Poletini, Maristela Oliveira; de Assis, Leonardo Vinicius Monteiro; Moraes, Maria Nathalia; Castrucci, Ana Maria de Lauro

    2016-10-01

    Melanin production within melanocytes is regulated, among others, by estradiol, whose effects on melanogenesis are still not completely elucidated. Here we show that although 10(-7) M 17β-estradiol (E2) increased tyrosinase mRNA levels in B16-F10 malignant melanocytes, there was a transient decrease and abolishment of the temporal variation of melanin content. Both parameters were much higher in the malignant than in normal Melan-a cells. Considering that silencing clock machinery in human melanocytes increases melanogenesis, we investigated clock gene expression in those cell lines. Except for Melan-a Bmal1 and B16-F10 Per2 expression of control cells, Per1, Per2, and Bmal1 expression increased independently of cell type or E2 treatment after 24 h. However, melanoma cells showed a marked increase in Per1 and Bma11 expression in response to E2 at the same time points, what may rule out E2 as a synchronizer agent since the expression of those genes were not in antiphase. Next, we investigated the expression of Xpa, a clock-controlled gene, which in Melan-a cells, peaked at 18 h, and E2 treatment shifted this peak to 24 h, whereas B16-F10 Xpa expression peaked at 24 h in both control and E2 group, and it was higher compared to Melan-a cells in both groups. Therefore, malignant and normal melanocytes display profound differences on core elements of the local clock, and how they respond to E2, what is most probably determinant of the differences seen on melanin synthesis and Tyrosinase and Xpa expression. Understanding these processes at the molecular level could bring new strategies to treat melanoma.

  2. Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response

    SciTech Connect

    Grdina, David J. Murley, Jeffrey S.; Kataoka, Yasushi; Baker, Kenneth L.; Kunnavakkam, Rangesh; Coleman, Mitchell C.; Spitz, Douglas R.

    2009-03-01

    Purpose: To determine whether amifostine can induce elevated manganese superoxide dismutase (SOD2) in murine tissues and a transplantable SA-NH tumor, resulting in a delayed tumor cell radioprotective effect. Methods and Materials: SA-NH tumor-bearing C3H mice were treated with a single 400 mg/kg or three daily 50 mg/kg doses of amifostine administered intraperitoneally. At selected time intervals after the last injection, the heart, liver, lung, pancreas, small intestine, spleen, and SA-NH tumor were removed and analyzed for SOD2, catalase, and glutathione peroxidase (GPx) enzymatic activity. The effect of elevated SOD2 enzymatic activity on the radiation response of SA-NH cells was determined. Results: SOD2 activity was significantly elevated in selected tissues and a tumor 24 h after amifostine treatment. Catalase and GPx activities remained unchanged except for significant elevations in the spleen. GPx was also elevated in the pancreas. SA-NH tumor cells exhibited a twofold elevation in SOD2 activity and a 27% elevation in radiation resistance. Amifostine administered in three daily fractions of 50 mg/kg each also resulted in significant elevations of these antioxidant enzymes. Conclusions: Amifostine can induce a delayed radioprotective effect that correlates with elevated levels of SOD2 activity in SA-NH tumor. If limited to normal tissues, this delayed radioprotective effect offers an additional potential for overall radiation protection. However, amifostine-induced elevation of SOD2 activity in tumors could have an unanticipated deleterious effect on tumor responses to fractionated radiation therapy, given that the radioprotector is administered daily just before each 2-Gy fractionated dose.

  3. 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.

  4. 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

  5. High intake of fatty fish, but not of lean fish, affects serum concentrations of TAG and HDL-cholesterol in healthy, normal-weight adults: a randomised trial.

    PubMed

    Hagen, Ingrid V; Helland, Anita; Bratlie, Marianne; Brokstad, Karl A; Rosenlund, Grethe; Sveier, Harald; Mellgren, Gunnar; Gudbrandsen, Oddrun A

    2016-08-01

    The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat.

  6. 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 ...

  7. 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.

  8. Listeners' Perceptions of Nonspeech Characteristics of Normal and Dysarthric Children.

    ERIC Educational Resources Information Center

    Lass, Norman J.; And Others

    1988-01-01

    The comparison of listeners' evaluations of nonspeech characteristics of eight dysarthric (due to cerebral palsy) and eight normal speaking children (ages 6-11) found that dysarthric speech adversely affected listeners' perceptions of the dysarthric speakers' personality and physical appearance characteristics. (Author/DB)

  9. The B-3 Ethylene Response Factor MtERF1-1 Mediates Resistance to a Subset of Root Pathogens in Medicago truncatula without Adversely Affecting Symbiosis with Rhizobia1[W][OA

    PubMed Central

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

    2010-01-01

    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. PMID:20713618

  10. Standardizing drug adverse event reporting data.

    PubMed

    Wang, Liwei; Jiang, Guoqian; Li, Dingcheng; Liu, Hongfang

    2013-01-01

    Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field.

  11. Prolactin decrease and shift to a normal-like isoform profile during treatment with quinagolide in a patient affected by an invasive prolactinoma.

    PubMed

    Guido, R; Valenti, S; Foppiani, L; De Martini, D; Cossu, M; Giusti, M

    1997-05-01

    Prolactin (PRL) circulates as multiple molecular weight variants: glycosylated phosphorylated, deamidated and sulphated forms. The profiles of the forms, as determined by isoelectrofocusing (IEF), differ in physiological and pathological conditions. The case of a 72-year-old woman affected by an invasive prolactinoma is described. The patient had undergone surgical treatment followed by radiotherapy at the age of 71 years. Bromocriptine therapy followed (up to 10 mg/die), but the PRL levels were still extremely high (over 13,000 micrograms/l as determined by IRMA, after dilution). We therefore treated the patient with quinagolide, at increasing dosages, from 150 micrograms/die on day 0 to 600 micrograms/die on day 220. This treatment progressively lowered PRL to 23.2 micrograms/l. In addition to a decrease in PRL levels, a progressive change in the IEF profile was also noted. Indeed, on day 0, the PRL isoforms were very acidic and during treatment they progressively shifted toward a more basic range. For purpose of comparison PRL profiles were also determined in 8 women with pathological hyperprolactinaemia (group A, aged 16-50 years, PRL levels: 25.1-170.4 micrograms/l), in 6 normal women (group B, aged 25-29 years, PRL levels: 3.4-7.9 micrograms/l) and in 5 normal women during a TRH test (group C, aged 17-52 years, PRL levels: 2.7-10.3 micrograms/l). The profiles observed in group A had a single major peak at isoelectric point (pI) 6.5, while the group B and C profiles were more heterogeneous displaying multiple minor peaks, the majority of the molecules being in a more basic range (pI 6.9 for group B and pI 7.5 for group C). During treatment, the profiles of our subject at first resembled those of group A; subsequently, when the PRL levels had normalised, the profile resembled those noted in group B. Altered (immature?, more glycosilated?, less bioactive?) PRL molecules could be secreted by the tumour. These data show that quinagolide successfully reduced PRL

  12. 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

  13. 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…

  14. Characterisation and distribution of epidermal growth factor receptors in equine hoof wall laminar tissue: comparison of normal horses and horses affected with chronic laminitis.

    PubMed

    Grosenbaugh, D A; Hood, D M; Amoss, M S; Williams, J D

    1991-05-01

    Epidermal growth factor (EGF) receptors were detected in plasma membrane preparations of equine hoof wall laminar tissue at concentrations comparable to that of equine liver. Scatchard analysis of the equilibrium binding data suggested the presence of two classes of EGF binding sites in most of the controls (plasma membranes from clinically normal horses); a high-affinity class and a more numerous low-affinity class. The dissociation constant of the low-affinity class of EGF-specific receptors (KD = 1 x 10(-9)M) is in reasonable agreement with other values established for the EGF receptor. The variability between individual estimates for the KD of the high-affinity receptor class precluded an accurate estimate for those sites. A possible explanation is discussed. The high-affinity binding sites were uniformly absent in plasma membranes prepared from horses affected by chronic laminitis. Autoradiographic analysis localised the EGF receptors primarily to the secondary epidermal laminae, with an apparent greater density over the proliferative basal keratinocytes. Little label was associated with the dermal or the keratinised primary epidermal laminae. Tissue from horses with chronic laminitis had EGF receptors located uniformly over the hyperplastic epidermal keratinocytes. These data suggest that an EGF-mediated response may be involved in the hyperproliferative response that is characteristic of chronic laminitis.

  15. Treatment with D-penicillamine or zinc sulphate affects copper metabolism and improves but not normalizes antioxidant capacity parameters in Wilson disease.

    PubMed

    Gromadzka, Grażyna; Grażyna, Gromadzka; Karpińska, Agata; Agata, Karpińska; Przybyłkowski, Adam; Adam, Przybyłkowski; Litwin, Tomasz; Tomasz, Litwin; Wierzchowska-Ciok, Agata; Agata, Wierzchowska-Ciok; Dzieżyc, Karolina; Karolina, Dzieżyc; Chabik, Grzegorz; Grzegorz, Chabik; Członkowska, Anna; Anna, Członkowska

    2014-02-01

    Copper accumulation in tissues due to a biallelic pathogenic mutation of the gene: ATP7B results in a clinical phenotype known as Wilson disease (WD). Aberrations in copper homeostasis can create favourable conditions for superoxide-yielding redox cycling and oxidative tissue damage. Drugs used in WD treatment aim to remove accumulated copper and normalise the free copper concentration in the blood. In the current study the effect of decoppering treatment on copper metabolism and systemic antioxidant capacity parameters was analyzed. Treatment naïve WD patients (TNWD) (n = 33), those treated with anti-copper drugs (TWD) (n = 99), and healthy controls (n = 99) were studied. Both TNWD and TWD patients characterised with decreased copper metabolism parameters, as well as decreased total antioxidant potential (AOP), glutathione (GSH) level, activity of catalase, glutathione peroxidase (GPx), and S-transferase glutathione, compared to controls. TWD patients had significantly lower copper metabolism parameters, higher total AOP and higher levels of GSH than TWD individuals; however, no difference was observed between these two patient groups with respect to the rest of the antioxidant capacity parameters. Patients who had undergone treatment with D-penicillamine or zinc sulphate did not differ with respect to copper metabolism or antioxidant capacity parameters, with the exception of GPx that was lower in D-penicillamine treated individuals. These data suggest that anti-copper treatment affects copper metabolism as well as improves, but does not normalize, natural antioxidant capacity in patients with WD. We propose to undertake studies aimed to evaluate the usefulness of antioxidants as well as selenium as a supplemental therapy in WD.

  16. Normal aging affects movement execution but not visual motion working memory and decision-making delay during cue-dependent memory-based smooth-pursuit.

    PubMed

    Fukushima, Kikuro; Barnes, Graham R; Ito, Norie; Olley, Peter M; Warabi, Tateo

    2014-07-01

    Aging affects virtually all functions including sensory/motor and cognitive activities. While retinal image motion is the primary input for smooth-pursuit, its efficiency/accuracy depends on cognitive processes. Elderly subjects exhibit gain decrease during initial and steady-state pursuit, but reports on latencies are conflicting. Using a cue-dependent memory-based smooth-pursuit task, we identified important extra-retinal mechanisms for initial pursuit in young adults including cue information priming and extra-retinal drive components (Ito et al. in Exp Brain Res 229:23-35, 2013). We examined aging effects on parameters for smooth-pursuit using the same tasks. Elderly subjects were tested during three task conditions as previously described: memory-based pursuit, simple ramp-pursuit just to follow motion of a single spot, and popping-out of the correct spot during memory-based pursuit to enhance retinal image motion. Simple ramp-pursuit was used as a task that did not require visual motion working memory. To clarify aging effects, we then compared the results with the previous young subject data. During memory-based pursuit, elderly subjects exhibited normal working memory of cue information. Most movement-parameters including pursuit latencies differed significantly between memory-based pursuit and simple ramp-pursuit and also between young and elderly subjects. Popping-out of the correct spot motion was ineffective for enhancing initial pursuit in elderly subjects. However, the latency difference between memory-based pursuit and simple ramp-pursuit in individual subjects, which includes decision-making delay in the memory task, was similar between the two groups. Our results suggest that smooth-pursuit latencies depend on task conditions and that, although the extra-retinal mechanisms were functional for initial pursuit in elderly subjects, they were less effective.

  17. Senescence-Associated Molecular and Epigenetic Alterations in Mesenchymal Stem Cell Cultures from Amniotic Fluid of Normal and Fetus-Affected Pregnancy

    PubMed Central

    Savickienė, Jūratė; Baronaitė, Sandra; Zentelytė, Aistė; Treigytė, Gražina

    2016-01-01

    Human amniotic-fluid-derived mesenchymal stem cells (AF-MSCs) are interesting for their multilineage differentiation potential and wide range of therapeutic applications due to the ease of culture expansion. However, MSCs undergo replicative senescence. So far, the molecular mechanisms that underlie fetal diseases and cell senescence are still poorly understood. Here, we analyzed senescence-associated morphologic, molecular, and epigenetic characteristics during propagation of MSCs derived from AF of normal and fetus-affected pregnancy. AF-MSCs cultures from both cell sources displayed quite similar morphology and expression of specific cell surface (CD44, CD90, and CD105) and stemness (Oct4, Nanog, Sox2, and Rex1) markers but had interindividual variability in proliferation capability and time to reach senescence. Within passages 4 and 8, senescent cultures exhibited typical morphological features, senescence-associated β-galactosidase activity, increased levels of p16, and decreased levels of miR-17 and miR-21 but showed differential expression of p21, p53, and ATM dependently on the onset of cell senescence. These differences correlated with changes in the level of chromatin modifiers (DNMT1 and HDAC1) and polycomb group proteins (EZH2, SUZ12, and BMI1) paralleling with changes in the expression of repressive histone marks (H3K9me3 and H3K27me3) and stemness markers (Oct4, Nanog, Sox2, and Rex1). Therefore epigenetic factors are important for AF-MSCs senescence process that may be related with individuality of donor or a fetus malignancy status. PMID:27803714

  18. 7 CFR 1900.55 - Adverse action procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS GENERAL Adverse Decisions and Administrative Appeals § 1900.55 Adverse action procedures. (a) If an applicant, guaranteed lender, a holder, borrower or grantee is adversely affected by a...

  19. 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…

  20. Evidence of multi-stage faulting by clay mineral analysis: Example in a normal fault zone affecting arkosic sandstones (Annot sandstones)

    NASA Astrophysics Data System (ADS)

    Buatier, Martine D.; Cavailhes, Thibault; Charpentier, Delphine; Lerat, Jérémy; Sizun, Jean Pierre; Labaume, Pierre; Gout, Claude

    2015-06-01

    Fault affecting silicoclastic sediments are commonly enriched in clay minerals. Clays are sensitive to fluid-rock interactions and deformation mechanisms; in this paper, they are used as proxy for fault activity and behavior. The present study focuses on clay mineral assemblages from the Point Vert normal fault zone located in the Annot sandstones, a Priabonian-Rupelian turbidite succession of the Alpine foredeep in SE France. In this area, the Annot sandstones were buried around 6-8 km below the front of Alpine nappes soon after their deposition and exhumed during the middle-late Miocene. The fault affects arkosic sandstone beds alternating with pelitic layers, and displays throw of about thirty meters. The fault core zone comprises intensely foliated sandstones bounding a corridor of gouge about 20 cm thick. The foliated sandstones display clay concentration along S-C structures characterized by dissolution of K-feldspar and their replacement by mica, associated with quartz pressure solution, intense microfracturation and quartz vein precipitation. The gouge is formed by a clayey matrix containing fragments of foliated sandstones and pelites. However, a detailed petrographical investigation suggests complex polyphase deformation processes. Optical and SEM observations show that the clay minerals fraction of all studied rocks (pelites and sandstones from the damage and core zones of the fault) is dominated by white micas and chlorite. These minerals have two different origins: detrital and newly-formed. Detrital micas are identified by their larger shape and their chemical composition with a lower Fe-Mg content than the newly-formed white micas. In the foliated sandstones, newly-formed white micas are concentrated along S-C structures or replace K-feldspar. Both types of newly formed micas display the same chemical composition confirmed microstructural observations suggesting that they formed in the same conditions. They have the following structural formulas: Na0

  1. Low-dose exposure to alkylphenols adversely affects the sexual development of Atlantic cod (Gadus morhua): acceleration of the onset of puberty and delayed seasonal gonad development in mature female cod.

    PubMed

    Meier, Sonnich; Morton, H Craig; Andersson, Eva; Geffen, Audrey J; Taranger, Geir Lasse; Larsen, Marita; Petersen, Marianne; Djurhuus, Rune; Klungsøyr, Jarle; Svardal, Asbjørn

    2011-09-01

    Produced water (PW), a by-product of the oil-production process, contains large amount of alkylphenols (APs) and other harmful oil compounds. In the last 20 years, there have been increasing concerns regarding the environmental impact of large increases in the amounts of PW released into the North Sea. We have previously shown that low levels of APs can induce disruption of the endocrine and reproductive systems of Atlantic cod (Gadus morhua). The aims of this follow-up study were to: (i) identify the lowest observable effect concentration of APs; (ii) study the effects of exposure to real PW, obtained from a North Sea oil-production platform; and (iii) study the biological mechanism of endocrine disruption in female cod. Fish were fed with feed paste containing several concentrations of four different APs (4-tert-butylphenol, 4-n-pentylphenol, 4-n-hexylphenol and 4-n-heptylphenol) or real PW for 20 weeks throughout the normal period of vitellogenesis in Atlantic cod from October to January. Male and female cod, exposed to AP and PW, were compared to unexposed fish and to fish fed paste containing 17β-oestradiol (E(2)). Approximately 60% of the females and 96% of the males in the unexposed groups were mature at the end of the experiment. Our results show that exposure to APs and E(2) have different effects depending on the developmental stage of the fish. We observed that juvenile females are advanced into puberty and maturation, while gonad development was delayed in both maturing females and males. The AP-exposed groups contained increased numbers of mature females, and significant differences between the untreated group and the AP-treated groups were seen down to a dose of 4 μg AP/kg body weight. In the high-dose AP and the E(2) exposed groups, all females matured and no juveniles were seen. These results suggest that AP-exposure can affect the timing of the onset of puberty in fish even at extremely low concentrations. Importantly, similar effects were not

  2. 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

  3. Adverse drug reactions.

    PubMed

    O'Reilly-Foley, Georgina

    2017-04-05

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.

  4. Nesfatin-130−59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions

    PubMed Central

    Prinz, Philip; Teuffel, Pauline; Lembke, Vanessa; Kobelt, Peter; Goebel-Stengel, Miriam; Hofmann, Tobias; Rose, Matthias; Klapp, Burghard F.; Stengel, Andreas

    2015-01-01

    Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130−59, was identified as active core of full length nesfatin-11−82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130−59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130−59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130−59 under conditions of diet-induced obesity (DIO). Male Sprague–Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130−59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130−59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130−59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4–8 h post injection (−29%) with the strongest reduction during the fifth hour (−75%), an effect detectable for 24 h (−12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130−59 was due to a reduction in meal size (−44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130−59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130−59 injected icv reduced food intake in the third hour post injection (−71%), an effect due to a reduced meal frequency (

  5. Nesfatin-130-59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions.

    PubMed

    Prinz, Philip; Teuffel, Pauline; Lembke, Vanessa; Kobelt, Peter; Goebel-Stengel, Miriam; Hofmann, Tobias; Rose, Matthias; Klapp, Burghard F; Stengel, Andreas

    2015-01-01

    Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130-59, was identified as active core of full length nesfatin-11-82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130-59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130-59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130-59 under conditions of diet-induced obesity (DIO). Male Sprague-Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130-59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130-59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130-59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4-8 h post injection (-29%) with the strongest reduction during the fifth hour (-75%), an effect detectable for 24 h (-12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130-59 was due to a reduction in meal size (-44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130-59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130-59 injected icv reduced food intake in the third hour post injection (-71%), an effect due to a reduced meal frequency (-27%, p < 0.05), while meal size was

  6. Early Adverse Experiences and the Developing Brain

    PubMed Central

    Bick, Johanna; Nelson, Charles A

    2016-01-01

    Children exposed to various forms of adversity early in life are at increased risk for a broad range of developmental difficulties, affecting both cognitive and emotional adjustment. We review a growing body of evidence suggesting that exposure to adverse circumstances affects the developing brain in ways that increase risk for a myriad of problems. We focus on two forms of adversity, one in which children are exposed to childhood maltreatment in family environments, and another in which children are exposed to extreme psychosocial deprivation in contexts of institutional rearing. We discuss ways in which each of these experiences represent violations of species-expected caregiving conditions, thereby imposing challenges to the developing brain. We also review emerging data pointing to the effectiveness of early intervention in remediating neurodevelopmental consequences associated with maltreatment or institutional rearing. We conclude by discussing implications of this work for public health efforts and highlight important directions for the field. PMID:26334107

  7. 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

  8. Adverse reactions to vaccines.

    PubMed

    Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M

    2003-06-01

    (The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

  9. FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung.

    PubMed

    Falvella, Felicia S; Frullanti, Elisa; Galvan, Antonella; Spinola, Monica; Noci, Sara; De Cecco, Loris; Nosotti, Mario; Santambrogio, Luigi; Incarbone, Matteo; Alloisio, Marco; Calabrò, Elisa; Pastorino, Ugo; Skaug, Vidar; Haugen, Aage; Taioli, Emanuela; Dragani, Tommaso A

    2009-06-15

    The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue.

  10. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions.

  11. Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin.

    PubMed

    Sidgwick, Gary P; Iqbal, Syed A; Bayat, Ardeshir

    2013-05-01

    Keloid disease (KD) is a fibroproliferative disorder characterised partly by an altered extracellular matrix (ECM) profile. In fetal scarring, hyaluronic acid (HA) expression is increased, but is reduced in KD tissue compared with normal skin (NS). The expression of Hyaluronan Synthase (HAS) and hyaluronidase (HYAL) in KD and NS tissue were investigated for the first time using a range of techniques. Hyaluronan synthase and HYAL mRNA expression were significantly increased in NS tissue compared with KD tissue (P < 0.05). Immunohistological analysis of tissue indicated an accumulation of HAS and HYAL protein expression in KD compared with NS due to the thicker epidermis. No differences were observed in mRNA or protein expression in KD and NS fibroblasts. Reduced expression of HAS and HYAL may alter HA synthesis, degradation and accumulation in KD. Better understanding of the role of HA in KD may lead to novel therapeutic approaches to address the resulting ECM imbalance.

  12. Chronic blockade of neuronal nitric oxide synthase does not affect long-term control of blood pressure in normal, saline-drinking or deoxycorticosterone-treated rats.

    PubMed

    Wangensteen, Rosemary; Sainz, Juan; Rodríguez-Gomez, Isabel; Moreno, Juan Manuel; Osuna, Antonio; Vargas, Félix

    2003-03-01

    It has been reported that long-term selective inhibition of neuronal nitric oxide synthase (nNOS) produces elevated blood pressure (BP) in normal rats. The present study was designed to analyse the possible influences of the sodium-retaining hormone deoxycorticosterone acetate (DOCA) and of an increased sodium intake on BP effects induced by the chronic blockade of nNOS with 7-nitroindazole (7NI). Two experiments were performed using 7NI at a dose of either 10 mg x kg(-1) x day(-1) (experiment 1) or 30 mg x kg(-1) x day(-1) (experiment 2). The following groups were used in both experiments: control rats, and rats that received either 1 % saline drinking water (Salt), deoxycorticosterone acetate (DOCA), 7NI, 7NI plus 1 % saline (7NI + Salt) or 7NI plus DOCA (7NI + DOCA). The tail systolic BP (SBP) was measured in all rats once a week. At the end of the experimental period, the mean arterial pressure (MAP) and metabolic, morphological and renal variables were measured. There were no significant differences in the tail SBP, final MAP or glomerular filtration rate between the experimental groups and the control group. In both experiments, the plasma renin activity (PRA) was significantly inhibited in the Salt groups and suppressed in the DOCA groups. The PRA significantly increased in the 7NI groups, whereas the 7NI + Salt and 7NI + DOCA groups showed a significant inhibition in PRA, especially compared to the 7NI groups in the two experiments. We conclude that chronic nNOS blockade is unable to increase BP in normal, saline-drinking or DOCA-treated rats. Furthermore, the nNOS blockade does not interfere with the counterbalance between renin and an increased sodium intake or retention.

  13. Adverse cutaneous drug reaction.

    PubMed

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.

  14. 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.

  15. Monoclonal antibody against a peptide of human prion protein discriminates between Creutzfeldt-Jacob's disease-affected and normal brain tissue.

    PubMed

    Curin Serbec, Vladka; Bresjanac, Mara; Popovic, Mara; Pretnar Hartman, Katrina; Galvani, Vesna; Rupreht, Ruth; Cernilec, Maja; Vranac, Tanja; Hafner, Iva; Jerala, Roman

    2004-01-30

    Current methods for diagnosing transmissible spongiform encephalopathies rely on the degradation of the cellular prion protein (PrP(C)) and the subsequent detection of the protease-resistant remnant of the pathological prion isoform PrP(Sc) by antibodies that react with all forms of PrP. We report on a monoclonal antibody, V5B2, raised against a peptide from the C-terminal part of PrP, which recognizes an epitope specific to PrP(Sc). In cryostat sections from Creutzfeldt-Jacob's disease (CJD) patients' brains, V5B2 selectively labels various deposits of PrP(Sc) without any pretreatment for removal of PrP(C). V5B2 does not bind to non-CJD brain samples or to recombinant PrP, either in its native or denatured form. Specificity for PrP is confirmed by a sandwich enzyme-linked immunosorbent assay utilizing V5B2, which discriminates between CJD and normal samples without proteinase K treatment, and by immunoprecipitation from CJD brain homogenate. The PrP(Sc)-specific epitope is disrupted by denaturation. We conclude that the C-terminal part of PrP in disease-associated PrP(Sc) aggregates forms a structural epitope whose conformation is distinct from that of PrP(C).

  16. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  17. Topical ceramides neither enhance UVB-induced apoptosis in normal human keratinocytes nor affect viability in UVB-irradiated reconstructed human epidermis.

    PubMed

    Grether-Beck, Susanne; Felsner, Ingo; Koehler, Tim; Farwick, Mike; Lersch, Peter; Rawlings, Anthony V; Krutmann, Jean

    2014-11-01

    Ceramides are the major lipid of lamellar sheets present in intercellular spaces of the stratum corneum contributing to epidermal barrier properties. Therefore, ceramides and their analogues have been studied for barrier enhancing and water-holding properties for decades. In vitro studies have indicated cytotoxic potential for cell-permeable ceramides thereby raising the question whether topical ceramide application might contribute to UVB-induced apoptosis. Phytosphingosine, N-hexanoyl-phytosphingosine and N-stearoylphytosphingosine (ceramide III) in concentrations ≤5 μm have been used for co-stimulation with low (160 J/m(2) ) or high (600 J/m(2) ) UVB doses in subconfluent basal and confluent differentiating keratinocytes. Significantly, increased caspase-3 activity was observed in basal keratinocytes irradiated with 600 J/m(2) UVB and in differentiating keratinocytes with both UVB doses. Co-stimulation with the named ceramides did not further increase (i) caspase-3 activity and (ii) nucleosomal fragmentation in differentiating keratinocytes. Moreover, co-stimulation with 1-mm ceramides did not further affect viability/lactate dehydrogenase release in UVB-irradiated reconstructed human epidermis corroborating the safety of these ceramides.

  18. Sensory-specific appetite is affected by actively smelled food odors and remains stable over time in normal-weight women.

    PubMed

    Ramaekers, Mariëlle G; Boesveldt, Sanne; Gort, Gerrit; Lakemond, Catriona M M; van Boekel, Martinus A J S; Luning, Pieternel A

    2014-08-01

    Understanding overconsumption starts with knowledge of how separate factors influence our eating behavior. Food cues such as food odors are known for their effect on general appetite and sensory-specific appetite (SSA). Active sniffing rather than passive exposure may induce satiation over time. The objective of this study was to investigate how actively sniffing banana odors affects general appetite, SSA, and subsequent food intake. In a crossover study, 61 women actively smelled cups containing natural banana, artificial banana odor, or water (no odor) for 10 min. Treatment order was randomly assigned as much as possible. General appetite and SSA were monitored by using 100-mm visual analog scales during the 10 min of active sniffing, followed by ad libitum intake of banana milkshake. Results showed that SSA was consistently high (+12 mm) during actively sniffing natural or artificial banana odors, with no decrease in SSA over time. Sniffing both banana odors increased the appetite for banana (+11 mm) and other sweet products (+4 mm), whereas the appetite for savory products decreased by 7 mm (all P < 0.01) compared with no odor. Actively sniffing banana odor did not significantly influence food intake (P = 0.68) or general appetite scores (P = 0.06). In conclusion, SSA scores during active sniffing were identical to the SSA found in a similar study that used passive smelling, suggesting that SSA is independent of the manner of sniffing and exposure time. Moreover, sweet/savory categorization may suggest that food odors communicate information about the nutrient composition of their associated foods. These data clearly show the appetizing effects of food odors.

  19. The Neurobiology of Intervention and Prevention in Early Adversity.

    PubMed

    Fisher, Philip A; Beauchamp, Kate G; Roos, Leslie E; Noll, Laura K; Flannery, Jessica; Delker, Brianna C

    2016-01-01

    Early adverse experiences are well understood to affect development and well-being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy.

  20. 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.

  1. 25 CFR 170.110 - How can State and local governments prevent discrimination or adverse impacts?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and adverse effects on tribes and Native American populations. (b) Examples of adverse effects include... excessive access to culturally or religiously sensitive areas; (3) Negatively affecting natural resources, trust resources, tribal businesses, religious, and cultural sites; (4) Harming indigenous plants...

  2. 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

  3. Adverse testicular effects of Botox® in mature rats

    SciTech Connect

    Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-03-01

    testicular spasms. • This study outlines possible testicular adverse effects of these injections. • Botox® affected normal testicular function and physiology. • Infertility is a serious problem that Botox® injections could cause.

  4. 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…

  5. Cutaneous adverse reactions to lenalidomide.

    PubMed

    Imbesi, S; Allegra, A; Calapai, G; Musolino, C; Gangemi, S

    2015-01-01

    Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide.

  6. 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

  7. Resiliency in the Face of Adversity: A Short Longitudinal Test of the Trait Hypothesis.

    PubMed

    Karaırmak, Özlem; Figley, Charles

    2017-01-01

    Resilience represents coping with adversity and is in line with a more positive paradigm for viewing responses to adversity. Most research has focused on resilience as coping-a state-based response to adversity. However, a competing hypothesis views resilience or resiliency as a trait that exists across time and types of adversity. We tested undergraduates enrolled in social work classes at a large southern university at two time periods during a single semester using measures of adversity, positive and negative affect, and trait-based resiliency. Consistent with the trait-based resiliency, and in contrast to state-based resilience, resiliency scores were not strongly correlated with adversity at both testing points but were with positive affect, and resiliency scores remained the same over time despite adversity variations. There was no gender or ethnic group difference in resilience scores. Black/African Americans reported significantly less negative affect and more positive affect than White/Caucasians.

  8. Adverse health effects of non-medical cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2009-10-17

    For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

  9. Exposure to organic solvents. Does it adversely affect pregnancy?

    PubMed Central

    McMartin, K. I.; Koren, G.

    1999-01-01

    QUESTION: One of my patients is a laboratory technician who routinely handles organic solvents. She has just learned that she is pregnant, and she depends very much on this job because her husband is unemployed. What is the risk to her unborn baby? ANSWER: Available epidemiologic data indicate your patient's fetus might be at increased risk for malformations. We recommend that she minimize her occupational exposure to organic solvents by routinely using ventilation systems and protective equipment. This is most important during the first trimester of pregnancy. PMID:10424263

  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. Combating adverse selection in secondary PC markets.

    PubMed

    Hickey, Stewart W; Fitzpatrick, Colin

    2008-04-15

    Adverse selection is a significant contributor to market failure in secondary personal computer (PC) markets. Signaling can act as a potential solution to adverse selection and facilitate superior remarketing of second-hand PCs. Signaling is a means whereby usage information can be utilized to enhance consumer perception of both value and utility of used PCs and, therefore, promote lifetime extension for these systems. This can help mitigate a large portion of the environmental impact associated with PC system manufacture. In this paper, the computer buying and selling behavior of consumers is characterized via a survey of 270 Irish residential users. Results confirm the existence of adverse selection in the Irish market with 76% of potential buyers being unwilling to purchase and 45% of potential vendors being unwilling to sell a used PC. The so-called "closet affect" is also apparent with 78% of users storing their PC after use has ceased. Results also indicate that consumers place a higher emphasis on specifications when considering a second-hand purchase. This contradicts their application needs which are predominantly Internet and word-processing/spreadsheet/presentation applications, 88% and 60% respectively. Finally, a market solution utilizing self monitoring and reporting technology (SMART) sensors for the purpose of real time usage monitoring is proposed, that can change consumer attitudes with regard to second-hand computer equipment.

  12. Multivariate normality

    NASA Technical Reports Server (NTRS)

    Crutcher, H. L.; Falls, L. W.

    1976-01-01

    Sets of experimentally determined or routinely observed data provide information about the past, present and, hopefully, future sets of similarly produced data. An infinite set of statistical models exists which may be used to describe the data sets. The normal distribution is one model. If it serves at all, it serves well. If a data set, or a transformation of the set, representative of a larger population can be described by the normal distribution, then valid statistical inferences can be drawn. There are several tests which may be applied to a data set to determine whether the univariate normal model adequately describes the set. The chi-square test based on Pearson's work in the late nineteenth and early twentieth centuries is often used. Like all tests, it has some weaknesses which are discussed in elementary texts. Extension of the chi-square test to the multivariate normal model is provided. Tables and graphs permit easier application of the test in the higher dimensions. Several examples, using recorded data, illustrate the procedures. Tests of maximum absolute differences, mean sum of squares of residuals, runs and changes of sign are included in these tests. Dimensions one through five with selected sample sizes 11 to 101 are used to illustrate the statistical tests developed.

  13. 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…

  14. Reverse engineering adverse outcome pathways.

    PubMed

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

    2011-01-01

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.

  15. Presence or absence of carbohydrates and the proportion of fat in a high-protein diet affect appetite suppression but not energy expenditure in normal-weight human subjects fed in energy balance.

    PubMed

    Veldhorst, Margriet A B; Westerterp, Klaas R; van Vught, Anneke J A H; Westerterp-Plantenga, Margriet S

    2010-11-01

    Two types of relatively high-protein diets, with a normal or low proportion of carbohydrates, have been shown effective for weight loss. The objective was to assess the significance of the presence or absence of carbohydrates and the proportion of fat in high-protein diets for affecting appetite suppression, energy expenditure, and fat oxidation in normal-weight subjects in energy balance. Subjects (aged 23 (sd 3) years and BMI 22·0 (sd 1·9) kg/m2) were stratified in two groups. Each was offered two diets in a randomised cross-over design: group 1 (n 22) - normal protein (NP; 10, 60 and 30 % energy (En%) from protein, carbohydrate and fat), high protein (HP; 30, 40 and 30 En%); group 2 (n 23) - normal protein (NP-g; 10, 60 and 30 En%), high protein, carbohydrate-free (HP-0C; 30, 0 and 70 En%) for 2 d; NP-g and HP-0C were preceded by glycogen-lowering exercise (day 1). Appetite was measured throughout day 2 using visual analogue scales (VAS). Energy expenditure (EE) and substrate oxidation (respiratory quotient; RQ) were measured in a respiration chamber (08.00 hours on day 2 until 07.30 hours on day 3). Fasting plasma β-hydroxybutyrate (BHB) concentration was measured (day 3). NP-g and NP did not differ in hunger, EE, RQ and BHB. HP-0C and HP v. NP-g and NP, respectively, were lower in hunger (P < 0·05; P < 0·001) and RQ (P < 0·01; P < 0·001) and higher in EE (P < 0·05; P = 0·07) and BHB (P < 0·05; P < 0·001). Hunger and RQ were lower with HP-0C than HP (693 (sd 208) v. 905 (sd 209) mm VAS × 24 h, P < 0·01; 0·76 (sd 0·01) v. 0·81 (sd 0·02), P < 0·01); BHB was higher (1349 (sd 653) v. 332 (sd 102) μmol/l; P < 0·001). ΔHunger, ΔRQ, and ΔBHB were larger between HP-0C-NP-g than between HP-NP ( - 346 (sd 84) v. - 107 (sd 52) mm VAS ×  24 h, P < 0·01; - 0·09 (sd 0·00) v. - 0·05 (sd 0·00), P < 0·001; 1115 (sd 627) v. 104 (sd 42) μmol/l, P < 0·001). In conclusion, appetite suppression and fat oxidation

  16. Adverse effects of isolation in hospitalised patients: a systematic review.

    PubMed

    Abad, C; Fearday, A; Safdar, N

    2010-10-01

    The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.

  17. Some effects of adverse weather conditions on performance of airplane antiskid braking systems

    NASA Technical Reports Server (NTRS)

    Horne, W. B.; Mccarty, J. L.; Tanner, J. A.

    1976-01-01

    The performance of current antiskid braking systems operating under adverse weather conditions was analyzed in an effort to both identify the causes of locked-wheel skids which sometimes occur when the runway is slippery and to find possible solutions to this operational problem. This analysis was made possible by the quantitative test data provided by recently completed landing research programs using fully instrumented flight test airplanes and was further supported by tests performed at the Langley aircraft landing loads and traction facility. The antiskid system logic for brake control and for both touchdown and locked-wheel protection is described and its response behavior in adverse weather is discussed in detail with the aid of available data. The analysis indicates that the operational performance of the antiskid logic circuits is highly dependent upon wheel spin-up acceleration and can be adversely affected by certain pilot braking inputs when accelerations are low. Normal antiskid performance is assured if the tire-to-runway traction is sufficient to provide high wheel spin-up accelerations or if the system is provided a continuous, accurate ground speed reference. The design of antiskid systems is complicated by the necessity for tradeoffs between tire braking and cornering capabilities, both of which are necessary to provide safe operations in the presence of cross winds, particularly under slippery runway conditions.

  18. D-Dimer elevation and adverse outcomes.

    PubMed

    Halaby, Rim; Popma, Christopher J; Cohen, Ander; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Goldhaber, Samuel Z; Hull, Russell; Hernandez, Adrian; Mentz, Robert; Harrington, Robert; Lip, Gregory; Peacock, Frank; Welker, James; Martin-Loeches, Ignacio; Daaboul, Yazan; Korjian, Serge; Gibson, C Michael

    2015-01-01

    D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

  19. Adverse drug reactions: part II.

    PubMed

    Wooten, James M

    2010-11-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.

  20. Adverse drug reactions: Part I.

    PubMed

    Wooten, James M

    2010-10-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.

  1. [Finasteride adverse effects: An update].

    PubMed

    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  2. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.

  3. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  4. Adverse food-drug interactions.

    PubMed

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.

  5. Systematic Analysis of Adverse Event Reports for Sex Differences in Adverse Drug Events

    PubMed Central

    Yu, Yue; Chen, Jun; Li, Dingcheng; Wang, Liwei; Wang, Wei; Liu, Hongfang

    2016-01-01

    Increasing evidence has shown that sex differences exist in Adverse Drug Events (ADEs). Identifying those sex differences in ADEs could reduce the experience of ADEs for patients and could be conducive to the development of personalized medicine. In this study, we analyzed a normalized US Food and Drug Administration Adverse Event Reporting System (FAERS). Chi-squared test was conducted to discover which treatment regimens or drugs had sex differences in adverse events. Moreover, reporting odds ratio (ROR) and P value were calculated to quantify the signals of sex differences for specific drug-event combinations. Logistic regression was applied to remove the confounding effect from the baseline sex difference of the events. We detected among 668 drugs of the most frequent 20 treatment regimens in the United States, 307 drugs have sex differences in ADEs. In addition, we identified 736 unique drug-event combinations with significant sex differences. After removing the confounding effect from the baseline sex difference of the events, there are 266 combinations remained. Drug labels or previous studies verified some of them while others warrant further investigation. PMID:27102014

  6. 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

  7. Adverse responses to local anaesthetics.

    PubMed

    Fisher, M M; Graham, R

    1984-11-01

    Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.

  8. Adverse Outcomes in Group Psychotherapy

    PubMed Central

    Roback, Howard B.

    2000-01-01

    Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions. PMID:10896735

  9. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    ERIC Educational Resources Information Center

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  10. The international serious adverse events consortium.

    PubMed

    Holden, Arthur L; Contreras, Jorge L; John, Sally; Nelson, Matthew R

    2014-11-01

    The International Serious Adverse Events Consortium is generating novel insights into the genetics and biology of drug-induced serious adverse events, and thereby improving pharmaceutical product development and decision-making.

  11. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  12. Adverse drug reactions in neonates: could we be documenting more?

    PubMed

    Hawcutt, Daniel B; O'Connor, Olya; Turner, Mark A

    2014-11-01

    Neonates are vulnerable to adverse drug reactions but reports of these events are relatively infrequent. Reporting can be increased by adapting a number of standard techniques to the unique features of neonatal care and pathology. However, clinicians and parents will be reluctant to report information about harms in the absence of mechanisms to ensure that reports affect clinical practice. Improved reporting will depend on education and cultural change that are informed by research about pharmacovigilance in neonatal settings. The efficient use of neonatal adverse drug reaction reports will require harmonization of terminology and interoperable databases.

  13. Weight-of-evidence evaluation of an adverse outcome ...

    EPA Pesticide Factsheets

    Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

  14. Adverse reactions to drug additives.

    PubMed

    Simon, R A

    1984-10-01

    There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.

  15. Do Holocaust survivors show increased vulnerability or resilience to post-Holocaust cumulative adversity?

    PubMed

    Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Shmotkin, Dov

    2010-06-01

    Prior trauma can hinder coping with additional adversity or inoculate against the effect of recurrent adversity. The present study further addressed this issue by examining whether a subsample of Holocaust survivors and comparison groups, drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe, were differentially affected by post-Holocaust cumulative adversity. Post-Holocaust cumulative adversity had a stronger effect on the lifetime depression of Holocaust survivors than on that of comparisons. However, comparisons were more negatively affected by post-Holocaust cumulative adversity when examining markers of physical and cognitive functioning. Our findings suggest that previous trauma can both sensitize and immunize, as Holocaust survivors show general resilience intertwined with specific vulnerability when confronted with additional cumulative adversity.

  16. Hypogonadism secondary to hyperprolactinaemia: successful treatment but adverse consequences.

    PubMed

    Narayanan, R P; Bujawansa, S; Qureshi, Z; Rimmer, M; Heald, A

    2012-05-01

    It is accepted that care must be taken in initiating testosterone replacement in hypogonadal individuals with historically low androgen levels. However less is reported about the influence of restoration of normal endogenous testosterone production on behaviour.Here we report how the adverse sequelae of successful treatment of hypogonadism secondary to hyperprolactinaemia, manifesting as irritability and low threshold to aggression, were managed through a joint approach between psychiatrist and physician.

  17. Omapatrilat normalizes renal function curve in spontaneously hypertensive rats

    PubMed Central

    Morazo, Paloma; Fortepiani, Lourdes A; Clara Ortíz, M; Atucha, Noemí M; García-Estañ, Joaquín

    2001-01-01

    Background The present study was designed to analyze the chronic renal response to omapatrilat, a new vasopeptidase inhibitor, in spontaneously hypertensive rats (SHR). To that end, the renal and blood pressure response to a 4-day salt loading protocol was analyzed and the respective chronic renal curves constructed. Results In non treated animals, and under normal sodium intake (around 2 mEq/day), mean arterial pressure (MAP), was significantly higher in the SHR as compared with the controls (WKY). After increasing salt intake (8 times normal), MAP did not change significantly in any group and the animals reached a normal sodium balance in four days. In a second group of animals, omapatrilat was given orally for 15 days at the dose of 40 mg/kg/day in the drinking water. In these omapatrilat-treated animals, and under normal sodium intake, MAP was significantly lower in both groups, although the antihypertensive effect was much greater in the SHR, so that the MAP of the SHR group was completely normalized and similar to the WKY-treated group. The subsequent elevation of sodium intake did not significantly elevate MAP in any group and the animals could manage the sodium excess as well as the non treated groups. Conclusions These results indicate that chronic treatment with omapatrilat normalizes blood pressure in SHR without affecting adversely the renal ability to eliminate a sodium load. Chronic treatment with omapatrilat resets the chronic pressure natriuresis relationship of the SHR to a normal level, thus without altering the normal salt-independence of this arterial hypertension model. PMID:11592920

  18. Early life adversity: Lasting consequences for emotional learning.

    PubMed

    Krugers, Harm J; Arp, J Marit; Xiong, Hui; Kanatsou, Sofia; Lesuis, Sylvie L; Korosi, Aniko; Joels, Marian; Lucassen, Paul J

    2017-02-01

    The early postnatal period is a highly sensitive time period for the developing brain, both in humans and rodents. During this time window, exposure to adverse experiences can lastingly impact cognitive and emotional development. In this review, we briefly discuss human and rodent studies investigating how exposure to adverse early life conditions - mainly related to quality of parental care - affects brain activity, brain structure, cognition and emotional responses later in life. We discuss the evidence that early life adversity hampers later hippocampal and prefrontal cortex functions, while increasing amygdala activity, and the sensitivity to stressors and emotional behavior later in life. Exposure to early life stress may thus on the one hand promote behavioral adaptation to potentially threatening conditions later in life -at the cost of contextual memory formation in less threatening situations- but may on the other hand also increase the sensitivity to develop stress-related and anxiety disorders in vulnerable individuals.

  19. 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.

  20. 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.

  1. Rethinking the Measurement of Adversity.

    PubMed

    Mersky, Joshua P; Janczewski, Colleen E; Topitzes, James

    2017-02-01

    Research on adverse childhood experiences (ACEs) has unified the study of interrelated risks and generated insights into the origins of disorder and disease. Ten indicators of child maltreatment and household dysfunction are widely accepted as ACEs, but further progress requires a more systematic approach to conceptualizing and measuring ACEs. Using data from a diverse, low-income sample of women who received home visiting services in Wisconsin ( N = 1,241), this study assessed the prevalence of and interrelations among 10 conventional ACEs and 7 potential ACEs: family financial problems, food insecurity, homelessness, parental absence, parent/sibling death, bullying, and violent crime. Associations between ACEs and two outcomes, perceived stress and smoking, were examined. The factor structure and test-retest reliability of ACEs was also explored. As expected, prevalence rates were high compared to studies of more representative samples. Except for parent/sibling death, all ACEs were intercorrelated and associated at the bivariate level with perceived stress and smoking. Exploratory factor analysis confirmed that conventional ACEs loaded on two factors, child maltreatment and household dysfunction, though a more complex four-factor solution emerged once new ACEs were introduced. All ACEs demonstrated acceptable test-retest reliability. Implications and future directions toward a second generation of ACE research are discussed.

  2. 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.

  3. Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

    PubMed

    St Louis, Erik K; Louis, Erik K

    2009-06-01

    The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

  4. OAE: The Ontology of Adverse Events

    PubMed Central

    2014-01-01

    Background A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. Conclusion OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of

  5. Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects

    PubMed Central

    Vyas, Purvi; Thakar, A. B.; Baghel, M. S.; Sisodia, Arvind; Deole, Yogesh

    2010-01-01

    Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy. PMID:22048532

  6. Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes

    PubMed Central

    Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D’ Amato, Francesca R.; Battaglia, Marco

    2016-01-01

    Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice’s respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders. PMID:27121911

  7. Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes.

    PubMed

    Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D' Amato, Francesca R; Battaglia, Marco

    2016-04-28

    Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice's respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders.

  8. 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

  9. Hospital deaths and adverse events in Brazil

    PubMed Central

    2011-01-01

    Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103) and that related to preventable adverse events was 2.3% (25/1103). Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43) and the odds ratio adjusted for patient risk factors (OR 8.23) between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events. PMID:21929810

  10. Characterizing "Adversity" of Pathology Findings in ...

    EPA Pesticide Factsheets

    The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This

  11. L-carnitine administration and withdrawal affect plasma and hepatic carnitine concentrations, plasma lipid and lipoprotein composition, and in vitro hepatic lipogenesis from labeled mevalonate and oleate in normal rabbits.

    PubMed

    Bell, F P; Vidmar, T J; Raymond, T L

    1992-04-01

    Carnitine was administered to normal rabbits to investigate the possible effects of pharmacologic doses on various aspects of normal lipid and lipoprotein metabolism. Carnitine concentrations were measured in the plasma and liver of normal rabbits that received L-carnitine orally [40 mg/(kg.d)] for 21 d and after withdrawal from the carnitine supplement for 21 d. Plasma lipids, plasma lipoprotein composition and in vitro hepatic lipid biosynthesis from [2-14C]mevalonate and [1-14C]oleate were also measured. Threefold elevations in plasma carnitine with carnitine treatment were essentially reversed after 48 h of carnitine withdrawal, but elevated hepatic carnitine accumulation (twofold) persisted for 21 d, suggesting that the accumulated carnitine constituted a pool that is only slowly miscible with plasma. The rabbits withdrawn from L-carnitine for 21 d experienced a 35% decrease in plasma cholesterol, a 50% decrease in VLDL cholesterol, and an increase in the protein content of HDL and of intermediate density lipoprotein + LDL. Additionally, the proportion of [14C]oleate incorporated into hepatic phospholipids increased 35% at the expense of triglyceride and the ratio of hepatic [14C]cholesterol to [14C]squalene derived from [14C]mevalonate increased over twofold following carnitine withdrawal. These studies provide evidence that normal lipid homeostasis can be altered by supplemental carnitine and that the perturbations are reflected by changes in plasma lipids and lipoproteins and in the proportions of the hepatic lipids synthesized.

  12. Neuroethics beyond Normal.

    PubMed

    Shook, John R; Giordano, James

    2016-01-01

    An integrated and principled neuroethics offers ethical guidelines able to transcend conventional and medical reliance on normality standards. Elsewhere we have proposed four principles for wise guidance on human transformations. Principles like these are already urgently needed, as bio- and cyberenhancements are rapidly emerging. Context matters. Neither "treatments" nor "enhancements" are objectively identifiable apart from performance expectations, social contexts, and civic orders. Lessons learned from disability studies about enablement and inclusion suggest a fresh way to categorize modifications to the body and its performance. The term "enhancement" should be broken apart to permit recognition of enablements and augmentations, and kinds of radical augmentation for specialized performance. Augmentations affecting the self, self-worth, and self-identity of persons require heightened ethical scrutiny. Reversibility becomes the core problem, not the easy answer, as augmented persons may not cooperate with either decommissioning or displacement into unaccommodating societies. We conclude by indicating how our four principles of self-creativity, nonobsolescence, empowerment, and citizenship establish a neuroethics beyond normal that is better prepared for a future in which humans and their societies are going so far beyond normal.

  13. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment.

    PubMed

    Kiff, Cara J; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J David; Mason, W Alex

    2012-06-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood.

  14. Adverse perinatal outcomes in borderline amniotic fluid index

    PubMed Central

    Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

    2016-01-01

    Background: Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. Objective: To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Materials and Methods: Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Results: Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. Conclusion: There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI. PMID:27981256

  15. The effect of simulated hamstring shortening on gait in normal subjects.

    PubMed

    Whitehead, C L; Hillman, S J; Richardson, A M; Hazlewood, M E; Robb, J E

    2007-06-01

    The purpose of this study was to determine the effect of simulated hamstring shortening on gait in normal subjects. Six normal subjects wore an adjustable brace to simulate three different hamstring lengths. Evaluation of the physiological cost index (PCI) and gait analysis revealed that simulated hamstring shortening produced adverse affects in the gait of normal subjects. Significant effects were only observed when the popliteal angle exceeded 85 degrees (p<0.001) and included increased effort of walking (PCI), decreased speed, stride and step length; decreased hip flexion and increased knee flexion in stance, increased posterior pelvic tilt, decreased pelvic obliquity and rotation and premature ankle dorsi- and plantar-flexion in stance. These results emphasise the need to consider the effects of changing the length of the hamstrings on joints other than the hip and knee when assessing patients for hamstring lengthening.

  16. 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

  17. 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...

  18. Adverse effects of cow's milk in infants.

    PubMed

    Ziegler, Ekhard E

    2007-01-01

    The feeding of cow's milk has adverse effects on iron nutrition in infants and young children. Several different mechanisms have been identified that may act synergistically. Probably most important is the low iron content of cow's milk. It makes it difficult for the infant to obtain the amounts of iron needed for growth. A second mechanism is the occult intestinal blood loss, which occurs in about 40% of normal infants during feeding of cow's milk. Loss of iron in the form of blood diminishes with age and ceases after 1 year of age. A third factor is calcium and casein provided by cow's milk in high amounts. Calcium and casein both inhibit the absorption of dietary nonheme iron. Infants fed cow's milk receive much more protein and minerals than they need. The excess has to be excreted in the urine. The high renal solute load leads to higher urine concentration during the feeding of cow's milk than during the feeding of breast milk or formula. When fluid intakes are low and/or when extrarenal water losses are high, the renal concentrating ability of infants may be insufficient for maintaining water balance in the face of high water use for excretion of the high renal solute. The resulting negative water balance, if prolonged, can lead to serious dehydration. There is strong epidemiological evidence that the feeding of cow's milk or formulas with similarly high potential renal solute load places infants at an increased risk of serious dehydration. The feeding of cow's milk to infants is undesirable because of cow's milk's propensity to lead to iron deficiency and because it unduly increases the risk of severe dehydration.

  19. Citrate anticoagulation and adverse events.

    PubMed

    De Vos, J; Hombrouckx, R

    2003-01-01

    Several patients with heparin intolerance were dialysed with tri-sodium citrate as anticoagulant without acute clinical problems (good tolerance). After some weeks however problems arose. In all patients an alkalosis developed: the pre dialysis bicarbonate level rose progressively from 27 mmol/l to 40 mmol/l. This could be tempered by lowering the dialysis fluid bicarbonate concentration from 37 mmol/l to 25 mmol/l. A second problem was a progressive rise in pre dialysis sodium level from a mean of 136 mmol/l to 150 mmol/l. Adapting the dialysis fluid sodium concentration from 140 mmol/l towards 132 mmol/l could solve this. The third problem was a progressive rise in serum aluminium level in patients from 3 microg/l to 38 microg/l. After excluding water, concentrate, dialysis fluid, drug intake, etc... as possible sources, we controlled the aluminium level in the glass bottle containing tri-sodium citrate. We noted the very high value of 35,300 microg/l. After replacing the glass bottles with polyvinylchloride bags with a negligible aluminium content, the serum aluminium levels returned back to normal. It is known that citrate chelates the aluminium present in the glass of bottles or vials.

  20. Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

    PubMed

    Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

    2017-02-01

    Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain.

  1. Defining "adverse environmental impact" and making paragraph 316(b) decisions: a fisheries management approach.

    PubMed

    Bailey, David E; Bulleit, Kristy A N

    2002-05-17

    The electric utility industry has developed an approach for decisionmaking that includes a definition of Adverse Environmental Impact (AEI) and an implementation process. The definition of AEI is based on lessons from fishery management science and analysis of the statutory term "adverse environmental impact" and is consistent with current natural resource management policy. The industry has proposed a definition focusing on "unacceptable risk to the population"s ability to sustain itself, to support reasonably anticipated commercial or recreational harvests, or to perform its normal ecological function." This definition focuses not on counting individual fish or eggs cropped by the various uses of a water body, but on preserving populations of aquatic organisms and their functions in the aquatic community. The definition recognizes that assessment of AEI should be site-specific and requires both a biological decision and a balancing of diverse societal values. The industry believes that the definition of AEI should be implemented in a process that will maximize the overall societal benefit of the paragraph 316(b) decision by considering the facility"s physical location, design, and operation, as well as the local biology. The approach considers effects on affected fish and shellfish populations and the benefits of any necessary best technology available (BTA) alternatives. This is accomplished through consideration of population impacts, which conversely allows consideration of the benefits of any necessary BTA modifications. This in turn allows selection of BTAs that will protect potentially affected populations in a cost-effective manner. The process also employs risk assessment with stakeholder participation, in accordance with EPA's Guidelines for Ecological Risk Assessment. The information and tools are now available to make informed decisions about site-specific impacts that will ensure protection of aquatic ecosystems and best serve the public interest.

  2. Mechanisms of injury to normal tissue after radiotherapy: a review

    PubMed Central

    Hubenak, Justin R.; Zhang, Qixu; Branch, Cynthia D.; Kronowitz, Steven J.

    2014-01-01

    Background The benefits of radiotherapy (RT) for cancer have been well documented for many years. However, even with targeted radiation delivery, many patients treated with radiation develop adverse effects. The purpose of this review was to analyze the current research into the biological basis of RT-induced normal tissue damage. Methods The PubMed and EMBASE databases were reviewed for articles on adverse effects of RT on normal tissue published from January 2005 through May 2012. Subsequently, abstracts of these articles were reviewed to identify articles with information relevant to the biological basis of RT-induced DNA damage and DNA repair. In addition, reference lists of the articles identified by the database search were reviewed, and referenced articles that seemed relevant were reviewed with no limitations on publication date. Results The database searches yielded 1751 publications. Of these, 1729 were eliminated because they did not address fundamental biology or were duplicates. A total of 22 articles were included. These articles revealed that many adverse effects are driven by chronic oxidative stress that affects the nuclear function of DNA repair mechanisms. Among normal cells undergoing replication, cells in S phase are most radioresistant because of overexpression of DNA repair enzymes, while cells in M phase are especially radiosensitive. Cancer cells exhibit increased radiosensitivity due to a breakdown in cell cycle checkpoints and repair mechanisms, and this increased radiosensitivity leads to accumulation of irreparable DNA lesions and cell death. Irradiated cells have an indirect effect on the cell cycle and survival of co-cultured non-irradiated cells. Method of irradiation and linear energy transfer to cancer cells versus bystander cells is shown to have an effect on cell survival, both cancerous and healthy. Conclusions RT-induced increases in reactive oxygen species in irradiated cells may signal healthy cells by increasing metabolic

  3. Synergistic childhood adversities and complex adult psychopathology.

    PubMed

    Putnam, Karen T; Harris, William W; Putnam, Frank W

    2013-08-01

    Numerous studies find a cumulative effect of different types of childhood adversities on increasing risk for serious adult mental and medical outcomes. This study uses the National Comorbidity Survey-Replication sample to investigate the cumulative impact of 8 childhood adversities on complex adult psychopathology as indexed by (a) number of lifetime diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994); (b) number of 4 DSM-IV disorder categories (mood, anxiety, impulse control, and substance abuse disorders); and (c) coexistence of internalizing and externalizing disorders. Seven of the 8 childhood adversities were significantly associated with complex adult psychopathology. Individuals with 4 or more childhood adversities had an odds ratio of 7.3, 95% confidence interval [4.7, 11.7] for 4 disorder categories. Additive and multiplicative synergistic effects increasing adult psychopathology were found for specific pairwise combinations of childhood adversities. Synergistic patterns differed by gender suggesting that women are more impacted by sexual abuse and men by economic hardship. The absence of childhood adversities was protective, in that it significantly decreased an individual's risk for subsequent adult mental illness. The results support the clinical impression that increased childhood adversity is associated with more complex adult psychopathology.

  4. Adverse event profile of tigecycline: data mining of the public version of the U.S. Food and Drug Administration adverse event reporting system.

    PubMed

    Kadoyama, Kaori; Sakaeda, Toshiyuki; Tamon, Akiko; Okuno, Yasushi

    2012-01-01

    The recent emergence of multidrug-resistant pathogens and/or pharmacokinetics-pharmacodynamics considerations may result in off-label use of a certain class of antibacterials, including tigecycline. This study was performed to clarify the safety profile of tigecycline in the user-derived manner and to compare it with the prescribing information provided by the manufacturer. Numerous spontaneous adverse event reports (AERs) submitted to the U.S. Food and Drug Administration (FDA) were analyzed after a revision of arbitrary drug names and the deletion of duplicated submissions. Standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Based on 22017956 co-occurrences, i.e., drug-adverse event pairs, found in 1644220 AERs from 2004 to 2009, 248 adverse events were suggested as tigecycline-associated ones. Adverse events with a relatively high frequency included nausea, vomiting, pancreatitis, hepatic failure, hypoglycemia, and increase in levels of alanine aminotransferase, bilirubin, alkaline phosphatase, aspartate aminotransferase, and gamma-glutamyltransferase. It is noted that cholestasis, jaundice, an increase in International Normalized Ratio, and Stevens-Johnson syndrome were also, although they were infrequent. The adverse events suggested were in agreement with information provided by the manufacturer, suggesting that off-label use hardly results in unexpected adverse events, presumably due to usage with extreme caution.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. [Cardiovascular pharmacotherapy. Risks and adverse effects].

    PubMed

    Voigt, N; Heijman, J; Dobrev, D

    2014-03-01

    Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

  12. 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

  13. Childhood adversity: a review of measurement instruments.

    PubMed

    Burgermeister, Diane

    2007-01-01

    Measurement instruments are needed to stimulate research on the long-term outcomes of childhood adversity. Therefore, the purpose of this review was to locate, describe, and assess instruments to measure retrospective perceptions of childhood adversity. An electronic search of instruments was conducted using a combination of keywords that included child maltreatment, child trauma, and childhood stressful events. Nine instruments were located and described according to format, definition of childhood adversity as measured by the instrument, characteristics of the sample used in development and testing, reliability and validity evidence, and feasibility for use. Six out of the nine instruments were suitable for investigators who require a comprehensive measure of childhood adversity. Corroboration with independent sources and use of randomized samples are needed to improve upon reports of validity.

  14. 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...

  15. 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...

  16. Design of Adverse Drug Events-Scorecards.

    PubMed

    Marcilly, Romaric; Chazard, Emmanuel; Beuscart-Zéphir, Marie-Catherine; Hackl, Werner; Băceanu, Adrian; Kushniruk, Andre; Borycki, Elizabeth M

    2011-01-01

    This paper presents the design of Adverse Drug Event-Scorecards. The scorecards described are innovative and novel, not having previously been reported in the literature. The Scorecards provide organizations (e.g. hospitals) with summary information about Adverse Drug Events (ADEs) using a Web-based platform. The data used in the Scorecards are routinely updated and report on ADEs detected through data mining processes. The development of the ADE Scorecards is ongoing and they are currently undergoing clinical testing.

  17. [Allergies and adverse events associated with fluoroquinolones].

    PubMed

    Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D

    2015-04-08

    The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

  18. Childhood adversity and frequent medical consultations.

    PubMed

    Fiddler, Maggie; Jackson, Judy; Kapur, Navneet; Wells, Adrian; Creed, Francis

    2004-01-01

    We assessed possible psychological mediators of the relationship between childhood adversity and frequent medical consultations among new outpatients at neurology, cardiology, and gastroenterology clinics. We assessed whether these differed in patients with and without organic disease that explained their symptoms. At first clinic visit we recorded Hospital Anxiety and Depression scale (HADS--anxiety and depression subscale scores), Illness Perception Questionnaire (IPQ--four subscales: consequences, cure, identity, timeline), Health Anxiety Questionnaire (total score), and Symptom Amplification Scale (total score). Subjects were divided into two groups according to whether they had experienced any type of childhood adversity using the Childhood Experience of Care and Abuse Schedule. Outcome was the (log) number of medical consultations for 12 months before and 6 months after the index clinic visits. Multiple regression analysis was used to determine mediators; this was performed separately for patients with symptoms explained and not explained by organic disease. One-hundred and twenty-nine patients (61% response) were interviewed. Fifty-two (40.3%) had experienced childhood adversity; they made a median of 16 doctor visits compared with 10 for those without adversity (adjusted P=.026). IPQ identity score (number of symptoms attributed to the illness) and HAD depression scores were significantly associated with both childhood adversity and number of medical consultations and these variables acted as mediators between childhood adversity and frequency of consultation in the multiple regression analyses. This association was limited to patients with medically unexplained symptoms and was mediated by IPQ Identity Score (number of symptoms attributed to the patient's illness) and HAD depression score. Sexual abuse and overt neglect were the adversities most closely associated with frequent consultations. In patients with medically unexplained symptoms the association

  19. Adverse drug reactions in hospitalized Colombian children

    PubMed Central

    Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

    2016-01-01

    Introduction: The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. Objective: To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. Methods: A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Results: Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p= 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p= 0.005). Conclusions: Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics. PMID:27821893

  20. Recognizing and reporting adverse drug reactions.

    PubMed Central

    Lucas, L. M.; Colley, C. A.

    1992-01-01

    Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient's clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient's medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA. PMID:1536067

  1. Adverse selection with a multiple choice among health insurance plans: a simulation analysis.

    PubMed

    Marquis, M S

    1992-08-01

    This study uses simulation methods to quantify the effects of adverse selection. The data used to develop the model provide information about whether families can accurately forecast their risk and whether this forecast affects the purchase of insurance coverage--key conditions for adverse selection to matter. The results suggest that adverse selection is sufficient to eliminate high-option benefit plans in multiple choice markets if insurers charge a single, experience-rated premium. Adverse selection is substantially reduced if premiums are varied according to demographic factors. Adverse selection is also restricted in supplementary insurance markets. In this market, supplementary policies are underpriced because a part of the additional benefits that purchasers can expect is a cost to the base plan and is not reflected in the supplementary premium. As a result, full supplementary coverage is attractive to both low and high risks.

  2. Affect is central to patient safety: the horror stories of young anaesthetists.

    PubMed

    Iedema, Rick; Jorm, Christine; Lum, Martin

    2009-12-01

    This paper analyses talk produced by twenty-four newly qualified anaesthetists. Data were collected from round table discussions at the Young Fellows Conference of the Australia and New Zealand College of Anaesthetists 2006. The talk consisted to an important extent of narratives about experiences of horror. The paper isolates three themes: the normalization of horror, the functionalisation of horror for pedagogic purposes, and the problematization of horror. The last theme provides a springboard into our argument that confronting the affect invested in coping with medical-clinical failure is central to enabling young doctors, and clinicians generally, to address and resolve such adverse events. We conclude that the negotiation of affect through shared or 'dialogic' narrative is central to enabling doctors to deal with adverse events on a personal level, and to enabling them at a collective level to become attentive to threats to patients' safety.

  3. Adverse drug events: database construction and in silico prediction.

    PubMed

    Cheng, Feixiong; Li, Weihua; Wang, Xichuan; Zhou, Yadi; Wu, Zengrui; Shen, Jie; Tang, Yun

    2013-04-22

    Adverse drug events (ADEs) are the harms associated with uses of given medications at normal dosages, which are crucial for a drug to be approved in clinical use or continue to stay on the market. Many ADEs are not identified in trials until the drug is approved for clinical use, which results in adverse morbidity and mortality. To date, millions of ADEs have been reported around the world. Methods to avoid or reduce ADEs are an important issue for drug discovery and development. Here, we reported a comprehensive database of adverse drug events (namely MetaADEDB), which included more than 520,000 drug-ADE associations among 3059 unique compounds (including 1330 drugs) and 13,200 ADE items by data integration and text mining. All compounds and ADEs were annotated with the most commonly used concepts defined in Medical Subject Headings (MeSH). Meanwhile, a computational method, namely the phenotypic network inference model (PNIM), was developed for prediction of potential ADEs based on the database. The area under the receive operating characteristic curve (AUC) is more than 0.9 by 10-fold cross validation, while the AUC value was 0.912 for an external validation set extracted from the US-FDA Adverse Events Reporting System, which indicated that the prediction capability of the method was reliable. MetaADEDB is accessible free of charge at http://www.lmmd.org/online_services/metaadedb/. The database and the method provide us a useful tool to search for known side effects or predict potential side effects for a given drug or compound.

  4. 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...

  5. 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.

  6. 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

  7. Adverse events temporally associated with meningococcal vaccines.

    PubMed Central

    Yergeau, A; Alain, L; Pless, R; Robert, Y

    1996-01-01

    OBJECTIVE: To determine the incidence of severe adverse events temporally associated with meningococcal vaccines administered as part of a mass vaccination program. DESIGN: Retrospective descriptive study of events reported to a passive provincial surveillance system. SETTING: The province of Quebec. PARTICIPANTS: The 1,198,751 individuals aged 6 months to 20 years who were vaccinated against meningococcal disease between Dec. 27, 1992, and Mar. 31, 1993. OUTCOME MEASURES: Total numbers and rates of severe adverse events, including allergic reactions, anaphylactic reactions, neurological events (other than abnormal crying and screaming) and other serious or unusual events. RESULTS: A total of 118 reports of severe adverse events were selected from the surveillance system. The most frequent were allergic reactions (9.2 per 100,000 doses). Few anaphylactic or neurologic reactions were reported (0.1 and 0.5 per 100,000 doses respectively). There were no reports of sequelae or of encephalopathy, meningitis or encephalitis. CONCLUSION: Meningococcal vaccines seem to be associated with fewer adverse events than have previously been reported. Existing surveillance programs are useful for determining the incidence of adverse events temporally associated with vaccines. PMID:8630839

  8. 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

  9. Is It Adverse, Nonadverse, Adaptive, or Artifact?

    PubMed

    Pandiri, Arun R; Kerlin, Roy L; Mann, Peter C; Everds, Nancy E; Sharma, Alok K; Myers, L Peyton; Steinbach, Thomas J

    2017-01-01

    One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA. The lectures at this course provided guidance on determining and communicating adversity using case studies involving both clinical pathology and anatomic pathology. In addition, one talk also focused on data quality, study design, and interpretation of artifacts that could hinder the determination of adversity. The CE course ended with a talk on understanding adversity in preclinical studies and engaging the regulatory agencies in the decision-making process. This manuscript is designed to provide brief summaries of all the talks in this well-received CE course.

  10. Environmental adversity and uncertainty favour cooperation

    PubMed Central

    Andras, Peter; Lazarus, John; Roberts, Gilbert

    2007-01-01

    Background A major cornerstone of evolutionary biology theory is the explanation of the emergence of cooperation in communities of selfish individuals. There is an unexplained tendency in the plant and animal world – with examples from alpine plants, worms, fish, mole-rats, monkeys and humans – for cooperation to flourish where the environment is more adverse (harsher) or more unpredictable. Results Using mathematical arguments and computer simulations we show that in more adverse environments individuals perceive their resources to be more unpredictable, and that this unpredictability favours cooperation. First we show analytically that in a more adverse environment the individual experiences greater perceived uncertainty. Second we show through a simulation study that more perceived uncertainty implies higher level of cooperation in communities of selfish individuals. Conclusion This study captures the essential features of the natural examples: the positive impact of resource adversity or uncertainty on cooperation. These newly discovered connections between environmental adversity, uncertainty and cooperation help to explain the emergence and evolution of cooperation in animal and human societies. PMID:18053138

  11. 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

  12. Adverse Family Experiences during Childhood and Adolescent Obesity

    PubMed Central

    Heerman, William J.; Krishnaswami, Shanthi; Barkin, Shari L.; McPheeters, Melissa

    2015-01-01

    Objective To evaluate the association between adverse family experiences (AFEs) during childhood and adolescent obesity and to determine populations at highest risk for adverse family experiences. Methods Cross sectional analysis of the 2011-2012 National Survey of Children’s Health, including children ages 10-17. Weighted estimates of 31,258,575 children were based on interviews with 42,239 caregivers. Caregiver-report of 9 psychosocial risk factors measured AFEs during childhood. Adolescent overweight and obesity were derived by caregiver-report of child height and weight. Results Nearly one-third (30.5%) of children had experienced ≥2 AFEs, with geographic variation by state. The prevalence of obesity among children experiencing ≥2 AFEs was 20.4%, compared with 12.5% among children with 0 AFEs. Adjusted survey regression models controlled for child, parent, household, and neighborhood characteristics. Children with ≥ 2 AFEs in childhood were more likely to be obese (AOR 1.8; 95% CI 1.47, 2.17; p<0.001) than those with no AFEs, with Non-Hispanic, White children most affected. Conclusions Adolescents in this national sample who were exposed to greater numbers of adverse family experiences in childhood also had higher rates of overweight and obesity. Geographic variation and differential associations based on race/ethnicity identify children at greatest risk. PMID:26853526

  13. 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.

  14. [Adverse reaction to not iodinated contrast].

    PubMed

    Palma-Gómez, Samuel; González-Díaz, Sandra Nora; Arias-Cruz, Alfredo; Macías-Weinmann, Alejandra; Amaro-Vivian, Laura Elizabeth; Pérez-Vanzzini, Rafael; Gutiérrez-Mujica, José Julio; Yong-Rodríguez, Adrián

    2014-01-01

    Adverse reactions to drugs are relatively frequent in clinical practice, and some of them can be life threatening. Reactions to contrast material (CM) represent an important percentage of these adverse reactions. It has been found that 70% of reactions to contrast material happen within the first five minutes of their administration. Despite the fact that hypersensitivity reactions are traditionally classified as non-allergic, in recent years investigators have reported positive skin prick tests in patients with immediate and late reactions to contrast material. This paper reports the case of a female patient with non-Hodgkin lymphoma that has presented on two distinct occasions adverse reactions to contrast material. We discuss on the type of reaction, severity, suggested prophylaxis, prognosis and recommendations, keeping in mind the underlying disease and the need to have further image studies performed.

  15. Adverse events related to blood transfusion.

    PubMed

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-09-01

    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.

  16. Adverse perinatal events associated with ART.

    PubMed

    Skora, Daniel; Frankfurter, David

    2012-04-01

    Since the advent of ART, much research has focused on the potential adverse for resultant harm. Prematurity, low birth-weight, PIH, congenital malformations, and CP are closely tied to multiple gestation. With the increase in elective single embryo transfer, there will be a reduction in adversity related to multiple birth. It is understood that underlying causes of infertility, including advanced maternal age, PCOS, thyroid disease, and uterine fibroids, predispose to adverse outcomes. However, imprinting abnormalities do not appear to stem from multiple births, and thus the need to consider the association between fertility treatment and methylation disorders remains essential. These, as well as risks of multi-fetal gestation, must be discussed with patients when considering using assisted reproduction.

  17. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity

    PubMed Central

    Cole, Steven W.; Levine, Morgan E.; Arevalo, Jesusa M. G.; Ma, Jeffrey; Weir, David R.; Crimmins, Eileen M.

    2015-01-01

    Background Chronic social adversity activates a conserved transcriptional response to adversity (CTRA) marked by increased expression of pro-inflammatory genes and decreased expression of antiviral- and antibody-related genes. Recent findings suggest that some psychological resilience factors may help buffer CTRA activation, but the relative impact of resilience and adversity factors remains poorly understood. Here we examined the relative strength of CTRA association for the two best-established psychological correlates of CTRA gene expression – the risk factor of perceived social isolation (loneliness) and the resilience factor of eudaimonic well-being (purpose and meaning in life). Methods Peripheral blood samples and validated measures of loneliness and eudaimonic well-being were analyzed in 108 community-dwelling older adults participating in the longitudinal US Health and Retirement Study (56% female, mean age 73). Mixed effect linear model analyses quantified the strength of association between CTRA gene expression and measures of loneliness and eudaimonic well-being in separate and joint analyses. Results As in previous studies, separate analyses found CTRA gene expression to be up-regulated in association with loneliness and down-regulated in association with eudaimonic well-being. In joint analyses, effects of loneliness were completely abrogated whereas eudaimonic well-being continued to associate with CTRA down-regulation. Similar eudaimonia-dominant effects were observed for positive and negative affect, optimism and pessimism, and anxiety symptoms. All results were independent of demographic and behavioral health risk factors. Conclusions Eudaimonic well-being may have the potential to compensate for the adverse impact of loneliness on CTRA gene expression. Findings suggest a novel approach to targeting the health risks associated with social isolation by promoting purpose and meaning in life. PMID:26246388

  18. [Normal aging and cognition].

    PubMed

    Ska, Bernadette; Joanette, Yves

    2006-03-01

    It is now well documented that normal aging modifies the cognitive functioning and most observations suggest that cognition evolves in the direction of deterioration. The more frequently impaired functions are memory, attention and visual-spatial abilities. On the other hand, some abilities seem to increase, such as vocabulary. Considering the aging effect on cognition, questions remain regarding directionality, universality and reversibility. A great variability in aged related impacts is observed among subjects and among cognitive domains. Some individuals evolved more rapidly than others. Some cognitive functions are more affected by aging than others. General and specific factors are hypothesized to explain the aged related cognitive decline. Among them, educational level, health, cognitive style, life style, personality, are likely to modulate the aged related cognitive evolution by influencing attentional resources and cerebral plasticity. Cognitive resources are essential to develop adaptative strategies. During the life span, resources are activated and increased by learning and training. Considering the role of cognitive resources, successful aging is dependent on several conditions : absence of disease leading to a loss of autonomy, maintenance of cognitive and physical activities, and active and social engaged lifestyle.

  19. Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death.

    PubMed

    LaLone, Carlie A; Villeneuve, Daniel L; Wu-Smart, Judy; Milsk, Rebecca Y; Sappington, Keith; Garber, Kristina V; Housenger, Justin; Ankley, Gerald T

    2017-04-15

    Ongoing honey bee (Apis mellifera) colony losses are of significant international concern because of the essential role these insects play in pollinating crops. Both chemical and non-chemical stressors have been implicated as possible contributors to colony failure; however, the potential role(s) of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptors (nAChRs) in the central nervous system to eliminate pest insects. However, mounting evidence indicates that neonicotinoids also may adversely affect beneficial pollinators, such as the honey bee, via impairments on learning and memory, and ultimately foraging success. The specific mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. The objective of this review was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between activation of the physiological target site, the nAChR, and colony level consequences. Potential for exposure was not a consideration in AOP development and therefore this effort should not be considered a risk assessment. Nonetheless, development of the AOPs described herein has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect normal colony functions, causing colony instability and subsequent bee population failure. A putative AOP network was developed, laying the foundation for further insights as to the role of combined chemical and non-chemical stressors in impacting bee populations. Insights gained from the AOP network assembly, which more realistically represents multi-stressor impacts on honey bee colonies, are

  20. 18 CFR 1301.19 - Appeals on initial adverse agency determination on correction or amendment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Appeals on initial... Water Resources TENNESSEE VALLEY AUTHORITY PROCEDURES Privacy Act § 1301.19 Appeals on initial adverse... to amend the records. Such statements normally should not exceed 100 words. A statement...

  1. Advocating for Normal Birth With Normal Clothes

    PubMed Central

    Waller-Wise, Renece

    2007-01-01

    Childbirth educators need to be aware that the clothes they wear when teaching classes send a nonverbal message to class participants. Regardless of who wears the clothing or what is worn, clothes send a message; thus, both the advantages and disadvantages related to clothing choice should be considered. Ultimately, the message should reflect the values of supporting normal birth. For childbirth educators who are allowed to choose their own apparel to wear in their classes, street clothes may be the benchmark for which to strive. This article discusses the many nonverbal messages that clothes convey and provides support for the choice of street clothes as the dress for the professional childbirth educator; thus, “normal clothes to promote normal birth.” PMID:18408807

  2. 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.

  3. 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:…

  4. Educational Leadership: The Uses of Adversity

    ERIC Educational Resources Information Center

    Culbertson, Jack

    1976-01-01

    Skepticism about the power of education challenges the educational administrator to (1) attain a better understanding of the sources of dissatisfaction and their implications for change, (2) learn to cope with adversity and make constructive use of it, and (3) define the leadership requirements needed to address education's problems. (MB)

  5. 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...

  6. Clinical spectrum of adverse reactions to tartrazine.

    PubMed

    Collins-Williams, C

    1985-01-01

    Tartrazine, a common additive in foods and drugs, often causes adverse reactions such as recurrent urticaria, angioedema, and asthma and is frequently implicated in hyperkinesis. This paper summarizes the recent literature on the subject and outlines a practical approach for the practicing physician to diagnose and treat these patients in an optimal manner.

  7. The Public Health Burden of Early Adversity

    ERIC Educational Resources Information Center

    Schlueter, Lisa J.; Watamura, Sarah Enos

    2017-01-01

    Severe and chronic stress in early childhood has enormous physical and mental health costs across an individual's lifespan. Unfortunately, exposure to early life adversity is common, and costs accrue to individuals and society. This article highlights several promising approaches to buffer children from the negative health consequences associated…

  8. [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.

  9. Adverse skin reactions following intravitreal bevacizumab injection

    PubMed Central

    Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A

    2011-01-01

    The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260

  10. Due Process in Adverse Personnel Action.

    ERIC Educational Resources Information Center

    Scriven, Michael

    1997-01-01

    A detailed checklist and timeline for ensuring due process are provided for adverse personnel actions, and the need to supplement this with expert, same-jurisdiction legal advice is stressed. This approach emphasizes the importance of treating due process as an ethical as well as a legal requirement. (SLD)

  11. 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...

  12. [Laser trabeculoplasty: therapeutic options and adverse effects].

    PubMed

    Wacker, T; Eckert, S

    2010-01-01

    Laser trabeculoplasty is a simple method for treating glaucoma and ocular hypertension and has few adverse effects. There are different laser systems for reducing the intraocular pressure of patients with glaucoma and ocular hypertension. Complications include transient intraocular pressure elevation, iritis, and anterior synechiae.

  13. 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…

  14. Adverse events of intravenous immunoglobulin infusions: a ten-year retrospective study

    PubMed Central

    Kwong, Shirley L.; Padua, Florecita R.

    2013-01-01

    Background Intravenous immunoglobulin (IVIG) is a biological product with adverse effects that appears to vary considerably among different IVIG preparations. Objectives To describe the adverse events of patients given intravenous immunoglobulin infusions. Method Data was collected on all patients receiving IVIG infusion at a tertiary hospital from January 2001 to December 2010. Descriptive statistics was used. Results 77 patients (45 males, 32 females) received IVIG infusions. Thirty two percent (n = 25) experienced adverse reactions. The most common indication was Kawasaki disease (85.7%) followed by immunodeficiency disorders (7.8%). Majority of the patients were children, with the highest frequency of infusions among those aged 2 to 8 years old (52%). 36 infusions were associated with occurrence of adverse effects. Fever was the most common adverse event (n = 11, 30.6%), followed by rash (n = 8, 22.2%) and chills (n = 7, 19.4%). Other adverse events were cyanosis (n = 3, 8.3%), hypotension (n = 2, 5.6%), hypothermia (n = 2, 5.6%), irritability (n = 1, 2.8%), vomiting (n = 1, 2.8%), and chest pain (n = 1, 2.8%). Adverse events were observed to occur most frequently within 1 to 6 h from onset of IVIG infusion. Among the various IVIG preparations available locally (Gammagard, Kiovig, Gamimune, Veno-S & IV Globulin S), Gammagard was the brand frequently used (50.7%). It also has the most number of adverse events, with 17 out of 41 (41.5%) infusions resulting in adverse reactions. Most of the reactions occurred with fast infusion rates, and clinical manifestations subsided when the rate of infusion was reduced. Conclusion In this study, thirty two percent of patients given IVIG infusions experienced adverse events. Fever was the most common manifestation. Symptoms occurred within 1 to 6 h from onset of infusion, were affected by fast infusion rates, and managed by reducing the rate of infusion. PMID:24260730

  15. 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...

  16. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 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...

  17. 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...

  18. 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...

  19. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 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...

  20. Quinolones: review of psychiatric and neurological adverse reactions.

    PubMed

    Tomé, Ana M; Filipe, Augusto

    2011-06-01

    of reports, while for ofloxacin and pefloxacin, the number of reports may be over-representative. A total of 232 ADRs were identified from the selected articles, with 206 of these related to psychiatric and/or neurological ADRs. The other 26 were related to other body systems but were reported together with the reactions of interest. Mania, insomnia, acute psychosis and delirium were the most frequently reported psychiatric adverse events; grand mal convulsion, confusional state, convulsions and myoclonus were the most frequently reported neurological adverse events. Several aspects should be taken into account in the development of CNS adverse effects, such as the pharmacokinetics of quinolones, chemical structure and quinolone uptake in the brain. These events may affect not only susceptible patients but also 'healthy' patients.

  1. Reading from a Head-Fixed Display during Walking: Adverse Effects of Gaze Stabilization Mechanisms

    PubMed Central

    Borg, Olivier; Casanova, Remy; Bootsma, Reinoud J.

    2015-01-01

    Reading performance during standing and walking was assessed for information presented on earth-fixed and head-fixed displays by determining the minimal duration during which a numerical time stimulus needed to be presented for 50% correct naming answers. Reading from the earth-fixed display was comparable during standing and walking, with optimal performance being attained for visual character sizes in the range of 0.2° to 1°. Reading from the head-fixed display was impaired for small (0.2-0.3°) and large (5°) visual character sizes, especially during walking. Analysis of head and eye movements demonstrated that retinal slip was larger during walking than during standing, but remained within the functional acuity range when reading from the earth-fixed display. The detrimental effects on performance of reading from the head-fixed display during walking could be attributed to loss of acuity resulting from large retinal slip. Because walking activated the angular vestibulo-ocular reflex, the resulting compensatory eye movements acted to stabilize gaze on the information presented on the earth-fixed display but destabilized gaze from the information presented on the head-fixed display. We conclude that the gaze stabilization mechanisms that normally allow visual performance to be maintained during physical activity adversely affect reading performance when the information is presented on a display attached to the head. PMID:26053622

  2. Reading from a Head-Fixed Display during Walking: Adverse Effects of Gaze Stabilization Mechanisms.

    PubMed

    Borg, Olivier; Casanova, Remy; Bootsma, Reinoud J

    2015-01-01

    Reading performance during standing and walking was assessed for information presented on earth-fixed and head-fixed displays by determining the minimal duration during which a numerical time stimulus needed to be presented for 50% correct naming answers. Reading from the earth-fixed display was comparable during standing and walking, with optimal performance being attained for visual character sizes in the range of 0.2° to 1°. Reading from the head-fixed display was impaired for small (0.2-0.3°) and large (5°) visual character sizes, especially during walking. Analysis of head and eye movements demonstrated that retinal slip was larger during walking than during standing, but remained within the functional acuity range when reading from the earth-fixed display. The detrimental effects on performance of reading from the head-fixed display during walking could be attributed to loss of acuity resulting from large retinal slip. Because walking activated the angular vestibulo-ocular reflex, the resulting compensatory eye movements acted to stabilize gaze on the information presented on the earth-fixed display but destabilized gaze from the information presented on the head-fixed display. We conclude that the gaze stabilization mechanisms that normally allow visual performance to be maintained during physical activity adversely affect reading performance when the information is presented on a display attached to the head.

  3. 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.

  4. Alleviation of adverse effects of drought stress on growth and some potential physiological attributes in maize (Zea mays L.) by seed electromagnetic treatment.

    PubMed

    Javed, Namra; Ashraf, Muhammad; Akram, Nudrat Aisha; Al-Qurainy, Fahad

    2011-01-01

    Effects of varying preseed magnetic treatments on growth, chlorophyll pigments, photosynthesis, water relation attributes, fluorescence and levels of osmoprotectants in maize plants were tested under normal and drought stress conditions. Seeds of two maize cultivars were treated with different (T0 [0 mT], T1 [100 mT for 5 min], T2 [100 mT for 10 min], T3 [150 mT for 5 min] and T4 [150 mT for 10 min]) electromagnetic treatments. Drought stress considerably suppressed growth, chlorophyll a and b pigments, leaf water potential, photosynthetic rate (A), stomatal conductance (g(s)) and substomatal CO(2) concentration (C(i)), while it increased leaf glycinebetaine and proline accumulation in both maize cultivars. However, pretreated seeds with different magnetic treatments significantly alleviated the drought-induced adverse effects on growth by improving chlorophyll a, A, E, g(s), C(i) and photochemical quenching and nonphotochemical quenching, while it had no significant effect on other attributes. However, different magnetic treatments negatively affected the g(s) and C(i) particularly in cv. Agaiti-2002 under drought stress conditions. Of all magnetic treatments, 100 and 150 mT for 10 min were most effective in alleviating the drought-induced adverse effects. Overall, preseed electromagnetic treatments could be used to minimize the drought-induced adverse effects on different crop plants.

  5. Innate immunity, coagulation and placenta-related adverse pregnancy outcomes.

    PubMed

    Li, Min; Huang, S Joseph

    2009-12-01

    Maternal immunity undergoes subtle adjustment in order to tolerate the semi-allogeneic embryo and maintain the host defense against potential pathogens. Concomitantly, coagulation systems change from an anti-coagulant state to a pro-coagulant state to meet the hemostatic challenge of placentation and delivery. Innate immunity and blood coagulation systems are the first line of defense to protect a host against exogenous challenges, including alloantigens and mechanical insults, and preserve the integrity of an organism. The interactions between coagulation and immune systems have been extensively studied. Immune cells play a pivotal role in the initiation of the coagulation cascade, whereas coagulation proteases display substantial immuno-modulatory effects. Upon exogenous challenges, the immune and coagulation systems are capable of potentiating each other leading to a vicious cycle. Natural killer (NK) cells, macrophages (Mphis) and dendritic cells (DCs) are three major innate immune cells that have been demonstrated to play essential roles in early pregnancy. However, immune maladaptation and hemostatic imbalance have been suggested to be responsible for adverse pregnant outcomes, such as preeclampsia (PE), miscarriage, recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR). In this review, we will summarize the mutual regulation between blood coagulation and innate immune systems as well as their roles in the maintenance of normal pregnancy and in the pathogenesis of adverse pregnancy outcomes.

  6. Ofloxacin Induced Angioedema: A Rare Adverse Drug Reaction

    PubMed Central

    Yadav, Sankalp; Kumar, Raj; Wani, Umar Rasool

    2016-01-01

    The Adverse Drug Reaction (ADR) to a commonly prescribed anti-microbial can pose a major public health problem. The authors report a rare case of 24-year-old young lady who presented with angioedema of lips after ingestion of Ofloxacin, prescribed to her for treatment of loose motions. Fluoroquinolones are widely prescribed antibiotics for various disease conditions. The history, clinical examination and normal laboratory parameters led to the diagnosis of ofloxacin induced hypersensitivity reaction and the patient was successfully treated with corticosteroids and antihistamines. The hypersensitivity reactions to fluoroquinolones are rare with an incidence of 0.4% to 2%. The pharmacovigilance program and self-reporting of all the ADR’s by the health care workers can help in ensuring the judicious use of the drug, drug safety and thus decrease the associated morbidity and mortality. PMID:28050397

  7. 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...

  8. 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...

  9. 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...

  10. Recurrent adverse pregnancy outcome and antiphospholipid antibodies.

    PubMed

    Reece, E A; Gabrielli, S; Cullen, M T; Zheng, X Z; Hobbins, J C; Harris, E N

    1990-07-01

    Antiphospholipid antibodies, which include lupus-like anticoagulant and anticardiolipin antibody, have been linked to a number of adverse pregnancy outcomes, although their exact pathogenic mechanisms remain poorly defined. The relative risk of complications such as intrauterine growth retardation, spontaneous abortions, and stillbirth in patients with antiphospholipid antibodies also remains undetermined. Heightened attention has been focused on the association, leading to investigations into the pathogenesis. Uncontrolled studies have also explored therapeutic regimens such as aspirin, steroids, and heparin, and clinical trials have used various treatment protocols. Although knowledge into the association of antiphospholipid antibodies and recurrent adverse pregnancy outcome is limited and continues to evolve, this association provides new insights into the disease and offers promise for pharmacologic prophylaxis. In this article, current concepts on pathogenesis, diagnosis, and therapy are reviewed and recommendations are made for clinical care of these patients.

  11. 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…

  12. Childhood Adversities and Adult Cardiometabolic Health: Does the Quantity, Timing, and Type of Adversity Matter?

    PubMed Central

    Friedman, Esther M.; Montez, Jennifer Karas; Sheehan, Connor McDevitt; Guenewald, Tara L.; Seeman, Teresa E.

    2015-01-01

    Objective Adverse events in childhood can indelibly influence adult health. While evidence for this association has mounted, a fundamental set of questions about how to operationalize adverse events has been understudied. Method We used data from the National Survey of Midlife Development in the United States to examine how quantity, timing, and types of adverse events in childhood are associated with adult cardiometabolic health. Results The best-fitting specification of quantity of events was a linear measure reflecting a dose–response relationship. Timing of event mattered less than repeated exposure to events. Regarding the type of event, academic interruptions and sexual/physical abuse were most important. Adverse childhood events elevated the risk of diabetes and obesity similarly for men and women but had a greater impact on women’s risk of heart disease. Discussion Findings demonstrate the insights that can be gleaned about the early-life origins of adult health by examining operationalization of childhood exposures. PMID:25903978

  13. Adverse Outcome Pathway (AOP) Network Development for ...

    EPA Pesticide Factsheets

    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 research. According to the Organization for Economic Co-operation and Development guidelines, AOPs are pathways with one MIE anchored to an adverse outcome (AO) by key events (KEs) and key event relationships (KERs). However, this approach does not always capture the cumulative impacts of multiple MIEs on the AO. For example, hepatic lipid flux due to chemical-induced toxicity initiates from multiple ligand-activated receptors and signaling pathways that cascade across biology to converge upon a common fatty liver (FL, also known as steatosis) outcome. To capture this complexity, a top-down strategy was used to develop a FL AOP network (AOPnet). Literature was queried based on the terms steatosis, fatty liver, cirrhosis, and hepatocellular carcinoma. Search results were analyzed for physiological and pathophysiological organ level, cellular and molecular processes, as well as pathway intermediates, to identify potential KEs and MIEs that are key for hepatic lipid metabolism, maintenance, and dysregulation. The analysis identified four apical KE nodes (hepatic fatty acid uptake, de novo fatty acid and lipid synthesis, fatty acid oxidation, and lipid efflux) juxtaposed to the FL AO. The apic

  14. Serious Adverse Events After Cataract Surgery

    PubMed Central

    Stein, Joshua D.

    2013-01-01

    Purpose Over the past several decades there have been many advances in the equipment, instrumentation and techniques of performing cataract surgery. This review will address the impact of these advances on the safety profile of cataract surgery. Recent Findings Recent studies have demonstrated a decline in the risk of serious postoperative adverse events (endophthalmitis, suprachoroidal hemorrhage, retinal detachment) following cataract surgery. Factors that increase the risk of serious complications from cataract surgery include patient-related factors (male sex, concomitant diabetic retinopathy, same day cataract surgery combined with another intraocular surgery, tamsulosin use) and surgeon-related factors (low surgical volume, limited experience, operating on patients who are most prone to adverse events). Summary Cataract surgery continues to be a very safe surgical procedure with few patients experiencing serious sight-threatening adverse events. Studies in the literature have helped surgeons identify patients who are at high risk for surgical complications and to develop strategies to limit surgical complications when operating on these patients. As multifocal intraocular lenses, femtosecond laser technology, and other surgical innovations continue to gain popularity, it will be interesting in the coming years to determine whether there will be a continued reduction in complications of cataract surgery. PMID:22450221

  15. Statin-Associated Muscle Adverse Events

    PubMed Central

    Al-Mohaissen, Maha A.; Ignaszewski, Martha J.; Frohlich, Jiri; Ignaszewski, Andrew P.

    2016-01-01

    Statins are potent medications which reduce low-density lipoprotein cholesterol (LDL-C) levels. Their efficacy in cardiovascular risk reduction is well established and indications for their use are expanding. While statins are generally well tolerated and safe, adverse events are relatively common, particularly statin-associated muscle adverse events (SaMAEs), which are the most frequently encountered type of adverse event. Recent guidelines and guideline updates on SaMAEs and statin intolerance have included revised definitions of SaMAEs, incorporating new evidence on their pathogenesis and management. As SaMAEs emerge as a therapeutic challenge, it is important for physicians to be aware of updates on management strategies to ensure better patient outcomes. The majority of patients who are considered statin-intolerant can nevertheless tolerate some forms of statin therapy and successfully achieve optimal LDL-C levels. This review article discusses the recent classification of SaMAEs with emphasis on pathogenesis and management strategies. PMID:28003885

  16. Metabolic and adverse effects of diuretics.

    PubMed

    Wilcox, C S

    1999-11-01

    Diuretics are among the most frequently prescribed drugs. They enjoy a very high clinical reputation for safety and efficacy. However, more than 3 decades of clinical investigation have disclosed a number of abnormalities in fluid electrolyte handling, metabolism, and other adverse effects that can complicate therapy with diuretic drugs. Some of these complications are a direct extension of the wanted action of the drug. These include extracellular fluid volume depletion, associated orthostatic hypotension, and prerenal azotemia. Others are not a direct action of the diuretic, but can be explained as an intranephronal compensation to the diuretic action. These include hypokalemia, in part to increased potassium secretion secondary to the enhanced tubular fluid flow and aldosterone secretion induced by diuretic administration. Metabolic abnormalities are usually mild. Hyperglycemia and carbohydrate intolerance have been related to diuretic-induced hypokalemia, which inhibits insulin secretion by the beta cells, and reductions in extracellular fluid volume and cardiac output. This is compounded by increases in catecholamines from sympathetic nerve activity which decrease peripheral glucose utilization. A mild increase in serum cholesterol concentration is seen frequently during initiation of diuretic therapy, but during steady state therapy after 6 to 12 months, values usually return to baseline. Knowledge of the more common adverse effects induced by diuretics helps the physician in predicting patients at risk and taking effective steps to anticipate or treat adverse responses.

  17. Genistein affects proliferation and migration of bovine oviductal epithelial cells.

    PubMed

    García, Daniela C; Valdecantos, Pablo A; Miceli, Dora C; Roldán-Olarte, Mariela

    2017-03-08

    Genistein is one of the most abundant isoflavones in soybean. This molecule induces cell cycle arrest and apoptosis in different normal and cancer cells. Genistein has been of considerable interest due to its adverse effects on bovine reproduction, altering estrous cycle, implantation and fetal development and producing subfertility or infertility. The objective of this work was to study the effects of genistein on the expression of selected genes involved in the regulation of cell cycle and apoptosis. Primary cultures of bovine oviductal epithelial cells (BOEC) were treated with different genistein concentrations (0.2, 2 and 10μM) to analyze CYCLIN B1, BCL-2 and BAX gene expression by Real-time RT-PCR. Results showed that genistein down-regulated CYCLIN B1 expression, affecting cell cycle progression, and caused a decrease in the BCL-2/BAX ratio starting at 2μM of genistein. In addition, in order to determine if genistein affects BOEC migration, in vitro wound healing assays were performed. A significant reduction in cell migration after 12h of culture was observed at both 0.2 and 10μM genistein concentrations. Also, in the presence of genistein the percentage of mitotic cells decreased, although apoptotic cells percentages were not affected. These findings indicate that genistein has an inhibitory effect on BOEC proliferation and migration, suggesting that it could influence the normal physiology of the oviductal epithelium.

  18. 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

  19. Normalized medical information visualization.

    PubMed

    Sánchez-de-Madariaga, Ricardo; Muñoz, Adolfo; Somolinos, Roberto; Castro, Antonio; Velázquez, Iker; Moreno, Oscar; García-Pacheco, José L; Pascual, Mario; Salvador, Carlos H

    2015-01-01

    A new mark-up programming language is introduced in order to facilitate and improve the visualization of ISO/EN 13606 dual model-based normalized medical information. This is the first time that visualization of normalized medical information is addressed and the programming language is intended to be used by medical non-IT professionals.

  20. Normal Shock Vortex Interaction

    DTIC Science & Technology

    2003-03-01

    Figure 9: Breakdown map for normal-shock vortex-interaction. References [1] O. Thomer, W. Schroder and M. Meinke , Numerical Simulation of Normal...and Oblique-Shock Vortex Interaction, ZAMM Band 80, Sub. 1, pp. 181-184, 2000. [2] O. Thomer, E. Krause, W. Schroder and M. Meinke , Computational

  1. Lidar monitoring of infrared target detection ranges through adverse weather

    NASA Astrophysics Data System (ADS)

    Bissonnette, Luc R.; Roy, Gilles; Theriault, Jean-Marc

    1998-11-01

    Despite recent technical advances, adverse weather still constitutes an important decision factor in the efficient use of IR sensors. The presence of fog, clouds or precipitation affects both the IR transmission and background properties of the atmosphere. Taking these effects into account requires the knowledge of the optical parameters of fog, clouds or precipitation which, in general, fluctuate too much on a scale of a few kilometers to be predictable with acceptable accuracy. Therefore, systems performance calculations based on modeling alone cannot provide all the necessary information for real time, on-site decision making. A promising alternative is continuous monitoring of atmospheric aerosol properties with a lidar. The method use in this study is the multiple-field- of-view technique which takes advantage of the information contained in the multiple scattering contributions to solve for both the droplet concentration and effective diameter. We can then use these solutions to derive the atmospheric radiance and transmittance, and calculate from there the contrast-to-noise ratio of IR images of small targets. Using actual lidar probings, examples of performance curves of a generic surveillance sensor are obtained for two types of targets. Results show that performance can drastically change over an interval as short as one minute, which emphasizes the need for real time, on site monitoring in adverse weather.

  2. Adverse drug reactions in special populations – the elderly

    PubMed Central

    Davies, E A; O’Mahony, M S

    2015-01-01

    The International Conference on Harmonization considers older people a ‘special population’, as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs. PMID:25619317

  3. Adverse mandibular bone effects associated with kidney disease are only partially corrected with bisphosphonate and/or calcium treatment

    PubMed Central

    Allen, Matthew R.; Chen, Neal X.; Gattone, Vincent H.; Moe, Sharon M.

    2014-01-01

    Background/Aims Patients with chronic kidney disease (CKD) have high prevalence of periodontal disease that may predispose to tooth loss and inflammation. The goal of this study was to test the hypotheses that a genetic rat model of progressive CKD would exhibit altered oral bone properties and that treatment with either bisphosphonates or calcium could attenuate these adverse changes. Methods At 25 weeks of age, rats were treated with zoledronate, calcium gluconate, or their combination for 5 or 10 weeks. Mandible bone properties were assessed using micro-computed tomography to determine bone volume (BV/TV) and cement-enamel junction to alveolar crest distance (CEJ-AC). Results Untreated CKD animals had significantly lower BV/TV at both 30 (−5%) and 35 (−14%) weeks of age and higher CEJ-AC (+27 and 29%) compared to normal animals. CKD animals had significantly higher PTH compared to normal animals yet similar levels of C-reactive protein. Zoledronate-treatment normalized BV/TV over the first 5 weeks but this benefit was lost by 10 weeks. Calcium treatment, alone or in combination with zoledronate, was effective in normalizing BV/TV at both time points. Neither zoledronate nor calcium was able to correct the higher CEJ-AC caused by CKD. Calcium, but not zoledronate, significantly reduced serum parathyroid hormone (PTH) while neither treatment affected C-reactive protein. Conclusions 1) this progressive animal model of chronic kidney disease shows a clear mandibular skeletal phenotype consistent with periodontitis, 2) the periodontitis is not associated with systemic inflammation as measured by C-reactive protein, and 3) reducing PTH has positive effects on the mandible phenotype. PMID:24280830

  4. The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

    ERIC Educational Resources Information Center

    Nicholi, Armand M., Jr.

    1983-01-01

    This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

  5. Adverse effects of statins - myths and reality.

    PubMed

    Šimić, Iveta; Reiner, Željko

    2015-01-01

    Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.

  6. Determinants of Adverse Events in Vascular Surgery

    PubMed Central

    Hernandez-Boussard, Tina; McDonald, Kathryn; Morton, John; Dalman, Ron L; Bech, Fritz R

    2016-01-01

    Background Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, which are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created. Study Design The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005–2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses. Results A total of 1,412,703 patients underwent a vascular procedure and 5.2% developed a PSI. PSIs were more frequent in female, non-white patients with public payers (p<.01). Patients at mid and low volume hospitals had greater odds of developing a PSI (Odds Ratio [OR], 1.17; 95% Confidence Interval [CI], 1.10–1.23 and OR, 1.69; CI, 1.53–1.87). Amputations had highest PSI risk-adjusted rate (RAR) and carotid endarterectomy and endovascular abdominal aortic aneurysm (AAA) repair had lower RAR (p<.0001). PSI RAR increased linearly by severity of patient indication: claudicants (OR, 0.40, CI, 0.35–0.46), rest pain patients (OR, 0.78, CI 0.69–0.90), ulcer (OR: 1.20, CI: 1.07–1.34) and gangrene patients (OR:1.85, CI: 1.66–2.06). Conclusions Patient safety events in vascular surgery were high and varied by procedure, with amputations and open AAA having substantially more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and appropriately adjust benchmarks for this surgical specialty. PMID:22425449

  7. 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.

  8. Joint Commission suspends 'auto' adverse decision.

    PubMed

    2010-08-01

    The Joint Commission's revision of its policy on root cause analysis puts greater attention of something that, quite frankly, some ED managers might not have been aware of. The ED manager plays an important role when events occur in the department, such as: knowing who the main Joint Commission contact is in the hospital, and making them aware of a potential adverse or sentinel event that has occurred; participating in the root cause analysis to identify what ED processes might need improvement; making sure the remedial activities recommended can be measured, so The Joint Commission can see an active attempt is being made to improve.

  9. 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

  10. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE.

  11. Mitigation of adverse environmental and unavoidable impacts

    SciTech Connect

    1995-10-01

    This portion of the Energy Vision 2020 draft report is a broad scope discussion of the mitigation of adverse environmental and unavoidable impacts. TVA will mitigate site specific environmental impacts from the construction and operation of new power facilities through a combination of planning, pollution prevention, and environmental controls. However, one of the most important mitigative measures associated with Energy Vision 2020 is the multi-attribute tradeoff method used for the evaluation. This method allowed proposed strategies to be reformated in order to reduce potential impacts.

  12. Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

    PubMed

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Temporal Resolution of the Normal Ear in Listeners with Unilateral Hearing Impairment.

    PubMed

    Mishra, Srikanta K; Dey, Ratul; Davessar, Jai Lal

    2015-12-01

    Unilateral hearing loss (UHL) leads to an imbalanced input to the brain and results in cortical reorganization. In listeners with unilateral impairments, while the perceptual deficits associated with the impaired ear are well documented, less is known regarding the auditory processing in the unimpaired, clinically normal ear. It is commonly accepted that perceptual consequences are unlikely to occur in the normal ear for listeners with UHL. This study investigated whether the temporal resolution in the normal-hearing (NH) ear of listeners with long-standing UHL is similar to those in listeners with NH. Temporal resolution was assayed via measuring gap detection thresholds (GDTs) in within- and between-channel paradigms. GDTs were assessed in the normal ear of adults with long-standing, severe-to-profound UHL (N = 13) and age-matched, NH listeners (N = 22) at two presentation levels (30 and 55 dB sensation level). Analysis indicated that within-channel GDTs for listeners with UHL were not significantly different than those for the NH subject group, but the between-channel GDTs for listeners with UHL were poorer (by greater than a factor of 2) than those for the listeners with NH. The hearing thresholds in the normal or impaired ears were not associated with the elevated between-channel GDTs for listeners with UHL. Contrary to the common assumption that auditory processing capabilities are preserved for the normal ear in listeners with UHL, the current study demonstrated that a long-standing unilateral hearing impairment may adversely affect auditory perception--temporal resolution--in the clinically normal ear. From a translational perspective, these findings imply that the temporal processing deficits in the unimpaired ear of listeners with unilateral hearing impairments may contribute to their overall auditory perceptual difficulties.

  18. 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

  19. 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

  20. 36 CFR 1010.10 - Actions that normally require an EA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... action that normally require an EA, but not necessarily an EIS, include: (1) Potential for degradation of environmental quality; (2) Potential for cumulative adverse impact on environmental quality; and (3) Potential for adverse impact on protected resources (e.g., natural, scenic, recreational, historical,...

  1. 36 CFR 1010.10 - Actions that normally require an EA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... action that normally require an EA, but not necessarily an EIS, include: (1) Potential for degradation of environmental quality; (2) Potential for cumulative adverse impact on environmental quality; and (3) Potential for adverse impact on protected resources (e.g., natural, scenic, recreational, historical,...

  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 (AOP) development and evaluation ...

    EPA Pesticide Factsheets

    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 measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar w

  4. [Adverse events of immune checkpoint inhibitors].

    PubMed

    Foller, S; Oppel-Heuchel, H; Fetter, I; Winkler, Y; Grimm, M-O

    2017-04-01

    After immune checkpoint inhibitor therapy was approved for renal cell carcinoma last year, this new immune therapy has spread to urology. Further approvals (atezolizumab, nivolumab, pembrolizumab) are expected in 2017 for metastatic urothelial carcinoma that has progressed following treatment with platinum-based chemotherapy. With expanding use of immune checkpoint inhibitors, experience in diagnosing and managing immune-mediated adverse events increases. Although of low incidence, grade 3/4 toxicities play a central role. Organs most common for immune-mediated adverse events are skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis), and endocrine organs (hyper-, hypothyroidism and hypophysitis). Diagnostic workup includes routine laboratory tests (including liver function tests) and may be supplemented with hormone values. In cases of pneumonitis or hypophysitis, imaging (high-resolution CT, MRI) can confirm diagnoses. Immune-mediated toxicities are treated with therapy interruption and administration of corticosteroids (and in individual cases additional immunosuppression). Dose modification is not intended!

  5. Adverse effects of new antiepileptic drugs.

    PubMed

    Onat, Filiz; Ozkara, Cigdem

    2004-04-01

    Starting with phenobarbital in the 1900s, it took almost 70-80 years to introduce old-generation agents for the treatment of epilepsy. Then, in eleven years, nine more new antiepileptic drugs were added to the armamentarium. These drugs produce a nearly 40-50% decrease in seizure incidence in refractory patients, but few patients have been able to achieve complete freedom from seizures. So the search for more effective drugs with minimal adverse effect profiles will continue. Although the new antiepileptic drugs do not demonstrate a superior efficacy compared to the older ones, they do offer some advantages in terms of tolerability, fewer drug interactions and simpler pharmacokinetics. However, our knowledge concerning their safety profiles can not yet be considered adequate due to the relatively short time these drugs have been on the market and to the limited number of patients exposed to them. The fact that the serious side effects of felbamate and vigabatrine appeared late after marketing should be taken as an important lesson because it implies the potential for unknown side effects at any time during treatment. Antiepileptic drug treatment should begin with diagnosis of the seizure and epileptic syndrome, followed by selection of the drug most appropriate for treatment of the individual patient, and continued with monitoring of not only the seizures but the adverse effect profile as well.

  6. 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

  7. Development of a Pediatric Adverse Events Terminology

    PubMed Central

    Gipson, Debbie S.; Kirkendall, Eric S.; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A.; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M.; Haber, Margaret; Hirschfeld, Steven

    2017-01-01

    In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute’s Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute’s Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization. PMID:28028203

  8. Development of a Pediatric Adverse Events Terminology.

    PubMed

    Gipson, Debbie S; Kirkendall, Eric S; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M; Haber, Margaret; Hirschfeld, Steven

    2017-01-01

    In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute's Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute's Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization.

  9. 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

  10. Accelerating Adverse Outcome Pathway (AOP) development ...

    EPA Pesticide Factsheets

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. However, the conventional process for assembly of these AOPs is time and resource intensive, and has been a rate limiting step for AOP use and development. Therefore computational approaches to accelerate the process need to be developed. We previously developed a method for generating computationally predicted AOPs (cpAOPs) by association mining and integration of data from publicly available databases. In this work, a cpAOP network of ~21,000 associations was established between 105 phenotypes from TG-GATEs rat liver data from different time points (including microarray, pathological effects and clinical chemistry data), 994 REACTOME pathways, 688 High-throughput assays from ToxCast and 194 chemicals. A second network of 128,536 associations was generated by connecting 255 biological target genes from ToxCast to 4,980 diseases from CTD using either HT screening activity from ToxCast for 286 chemicals or CTD gene expression changes in response to 2,330 chemicals. Both networks were separately evaluated through manual extraction of disease-specific cpAOPs and comparison with expert curation of the relevant literature. By employing data integration strategies that involve the weighting of n

  11. PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework proceeds from a general (e.g., not chemical specific) molecular mode of action, designated as a MIE, through stepwise changes in biological status, defined as key events (KEs), to a final AO that can be used in risk assessment. Because aromatase-inhibiting pharmaceuticals are widely used to treat breast cancer patients, we explored the unintended consequences that might occur in fish exposed to these chemicals through wastewater discharge into the aquatic environment. Unlike mammals, fish have two isoforms of aromatase, one that predominates in the ovary (cyp19a1a) and a second (cyp19a1b) that prevails in the brain. Aromatase activity in fish brain can be 100 to 1000 times that in mammals and is associated with reproduction. We have developed a putative AOP for inhibition of brain aromatase in fish leading to reproductive dysfunction based on review of relevant literature and reproductive experiments with the marine fish cunner (Tautogolabrus adspersus) exposed to aromatase-inhibiting pharmaceuticals in the laboratory. The first KE in this AOP is a decrease in brain aromatase activity due to exposure to an aromatase inhibitor. KEs then progress through subsequent steps including decreas

  12. Normality in Analytical Psychology

    PubMed Central

    Myers, Steve

    2013-01-01

    Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity. PMID:25379262

  13. Normal Pressure Hydrocephalus

    MedlinePlus

    ... techniques and neuroimaging, and finding improved treatments and preventions. Information from the National Library of Medicine’s MedlinePlus Normal Pressure Hydrocephalus × What research is being ...

  14. Normal Functioning Family

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  15. The adverse effects profile of levetiracetam in epilepsy: a more detailed look.

    PubMed

    Mbizvo, Gashirai K; Dixon, Pete; Hutton, Jane L; Marson, Anthony G

    2014-09-01

    The adverse effects profile of levetiracetam in epilepsy is still being fully described. We recently published a Cochrane Review evaluating the effectiveness of levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy. The five most common adverse effects were reported and analysed with no scope for reporting any less common adverse effects than those. Here, we report and analyse the remaining adverse effects (including the five most common). These were (in decreasing order of frequency) somnolence; headache; asthenia; accidental injury; dizziness; infection; pharyngitis; pain; rhinitis; abdominal pain; flu syndrome; vomiting; diarrhoea; convulsion; nausea; increased cough; anorexia; upper respiratory tract infection; hostility; personality disorder; urinary tract infection; nervousness; depression; aggression; back pain; agitation; emotional liability; psychomotor hyperactivity; pyrexia; rash; ECG abnormalities; decreased appetite; nasal congestion; irritability; abnormal behaviour; epistaxis; insomnia; altered mood; anxiety; bloody urine; diplopia; dissociation; memory impairment; pruritis; increased appetite; acne; and stomach discomfort. Only somnolence and infection were significantly associated with levetiracetam. When adverse effects pertaining to infection were combined, these affected 19.7% and 15.1% of participants on levetiracetam and placebo (relative risk 1.16, CI 0.89-1.50, Chi(2) heterogeneity p = 0.13). Somnolence and infection further retained significance in adults while no single adverse effect was significant in children. This review updates the adverse effects profile data on levetiracetam use by empirically reporting its common and uncommon adverse effects and analysing their relative importance statistically using data from a group of trials that possess low Risk of Bias and high Quality of Evidence GRADE scores.

  16. 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

  17. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  18. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  19. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  20. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  1. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  2. 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,...

  3. 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...

  4. 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...

  5. Apparent diffusion coefficient normalization of normal liver

    PubMed Central

    Zhu, Jie; Zhang, Jie; Gao, Jia-Yin; Li, Jin-Ning; Yang, Da-Wei; Chen, Min; Zhou, Cheng; Yang, Zheng-Han

    2017-01-01

    Abstract Apparent diffusion coefficient (ADC) measurement in diffusion-weighted imaging (DWI) has been reported to be a helpful biomarker for detection and characterization of lesion. In view of the importance of ADC measurement reproducibility, the aim of this study was to probe the variability of the healthy hepatic ADC values measured at 3 MR scanners from different vendors and with different field strengths, and to investigate the reproducibility of normalized ADC (nADC) value with the spleen as the reference organ. Thirty enrolled healthy volunteers received DWI with GE 1.5T, Siemens 1.5T, and Philips 3.0T magnetic resonance (MR) systems on liver and spleen (session 1) and were imaged again after 10 to 14 days using only GE 1.5T MR and Philips 3.0T MR systems (session 2). Interscan agreement and reproducibility of ADC measurements of liver and the calculated nADC values (ADCliver/ADCspleen) were statistically evaluated between 2 sessions. In session 1, ADC and nADC values of liver were evaluated for the scanner-related variability by 2-way analysis of variance and intraclass correlation coefficients (ICCs). Coefficients of variation (CVs) of ADCs and nADCs of liver were calculated for both 1.5 and 3.0-T MR system. Interscan agreement and reproducibility of ADC measurements of liver and related nADCs between 2 sessions were found to be satisfactory with ICC values of 0.773 to 0.905. In session 1, the liver nADCs obtained from different scanners were consistent (P = 0.112) without any significant difference in multiple comparison (P = 0.117 to >0.99) by using 2-way analysis of variance with post-hoc analysis of Bonferroni method, although the liver ADCs varied significantly (P < 0.001). nADCs measured by 3 scanners were in good interscanner agreements with ICCs of 0.685 to 0.776. The mean CV of nADCs of both 1.5T MR scanners (9.6%) was similar to that of 3.0T MR scanner (8.9%). ADCs measured at 3 MR scanners with different field strengths and vendors

  6. 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

  7. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function

    PubMed Central

    Anacker, Christoph; O'Donnell, Kieran J.; Meaney, Michael J.

    2014-01-01

    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. PMID:25364283

  8. 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.

  9. Transgenerational transmission of pregestational and prenatal experience: maternal adversity, enrichment, and underlying epigenetic and environmental mechanisms.

    PubMed

    Taouk, L; Schulkin, J

    2016-12-01

    Transgenerational transmission refers to positive and negative adaptations in brain function and behavior that affect following generations. In this paper, empirical findings regarding the transgenerational transmission of maternal adversity during three critical periods - childhood, pregestational adulthood and pregnancy - will be reviewed in terms of pregnancy outcomes, maternal care, offspring behavior and development, and physiological functioning. Research on the transgenerational transmission of enrichment and the implications for interventions to ameliorate the consequences of adversity will also be presented. In the final section, underlying epigenetic and environmental mechanisms that have been proposed to explain how experience is transferred across generations through transgenerational transmission will be reviewed. Directions for future research are suggested throughout.

  10. 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

  11. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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) Apply criteria of adverse effect. In consultation with the SHPO/THPO and any Indian tribe or Native...

  12. 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...

  13. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 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....

  14. 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

  15. 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

  16. Adverse Risks Associated With Proton Pump Inhibitors

    PubMed Central

    2009-01-01

    Proton pump inhibitors (PPIs) are among the most commonly utilized agents for treatment of symptomatic disorders of the upper gastrointestinal tract, accounting for a significant proportion of sales of both over-the-counter and prescription formulations. A systematic review of the literature was conducted via MEDLINE to evaluate the most rigorous studies linking the potential risk of PPI therapy with adverse events. Emerging data illustrate the potential risks associated with both short-and long-term PPI therapy, including Clostridium difficile–associated diarrhea, community-acquired pneumonia, osteoporotic fracture, vitamin B12 deficiency, and inhibition of antiplatelet therapy. Due to these associations, it is recommended that clinicians assess the continuing need for PPI therapy and use the lowest possible dose to achieve the desired therapeutic goals.

  17. Vaccine adverse events: separating myth from reality.

    PubMed

    Kimmel, Sanford R

    2002-12-01

    Vaccines have turned many childhood diseases into distant memories in industrialized countries. However, questions have been raised about the safety of some vaccines because of rare but serious adverse effects that have been attributed to them. Pain, swelling, and redness at the injection site are common local reactions to vaccines. Fever and irritability may occur after some immunizations. Currently, no substantial evidence links measles-mumps-rubella vaccine to autism, or hepatitis B vaccine to multiple sclerosis. Thimerosal is being eliminated from routine childhood vaccines because of concerns that multiple immunizations with vaccines containing this preservative could exceed recommended mercury exposures. Family physicians should be knowledgeable about vaccines so that they can inform their patients of the benefits of immunization and any proven risks. If immunization rates fall, the incidence of vaccine-preventable illnesses may rise.

  18. Quantifying surface normal estimation

    NASA Astrophysics Data System (ADS)

    Reid, Robert B.; Oxley, Mark E.; Eismann, Michael T.; Goda, Matthew E.

    2006-05-01

    An inverse algorithm for surface normal estimation from thermal polarimetric imagery was developed and used to quantify the requirements on a priori information. Building on existing knowledge that calculates the degree of linear polarization (DOLP) and the angle of polarization (AOP) for a given surface normal in a forward model (from an object's characteristics to calculation of the DOLP and AOP), this research quantifies the impact of a priori information with the development of an inverse algorithm to estimate surface normals from thermal polarimetric emissions in long-wave infrared (LWIR). The inverse algorithm assumes a polarized infrared focal plane array capturing LWIR intensity images which are then converted to Stokes vectors. Next, the DOLP and AOP are calculated from the Stokes vectors. Last, the viewing angles, θ v, to the surface normals are estimated assuming perfect material information about the imaged scene. A sensitivity analysis is presented to quantitatively describe the a priori information's impact on the amount of error in the estimation of surface normals, and a bound is determined given perfect information about an object. Simulations explored the impact of surface roughness (σ) and the real component (n) of a dielectric's complex index of refraction across a range of viewing angles (θ v) for a given wavelength of observation.

  19. Adverse Environments and Children's Creativity Development: Transforming the Notion of "Success in Adversity" in China

    ERIC Educational Resources Information Center

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications…

  20. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

    Soukavong, Mick; Kim, Jungmee; Park, Kyounghoon; Yang, Bo Ram; Lee, Joongyub; Jin, Xue Mei; Park, Byung Joo

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability.

  1. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

    PubMed Central

    2016-01-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  2. Environmental factors affecting chemoreceptors: an overview.

    PubMed

    Halpern, B P

    1982-04-01

    Vertebrate olfactory and gustatory receptors are necessarily exposed to the fluid which contains their relevant chemosensory environment. In terrestrial mammals, the nasal airways serve as protective accessory tissues for the olfactory receptors, but tastes receptors in all vertebrates and olfactory receptors in fish are directly exposed to the liquids which bring chemosensory stimuli to them. The differentiated epithelial cells which form taste buds and the specialized neurons which are the vertebrate olfactory receptors are constantly replaced in normal adult animals, suggesting that chemosensory function per se is damaging to the receptors. Organic and sulfur-containing air pollutants may be among those which adversely affect olfactory receptors, but adequate data are not available. Surfactants and heavy metals can produce physiological and/or morphological damage in gustatory receptors. Some heavy metals are concentrated in saliva, a liquid which interacts closely with taste receptors. A failure to evaluate human chemosensory function in relation to potential chemosensory toxicants accounts for the present inability to specify the incidence of the problem.

  3. Effects of whole body vibration on spinal proprioception in normal individuals.

    PubMed

    Lee, T Y; Chow, D H K

    2013-01-01

    Low back pain (LBP) is a common health problem with high reoccurrence rate. While most LBP cases are classified as non-specific, patients in general often present impaired proprioception. Whole body vibration (WBV) has been proven to improve muscle function and proprioception in the lumbo-pelvic region. The aim of this study was to determine whether WBV would affect spinal proprioception. Eleven young normal individuals were recruited. Their body alignment, lumbar repositioning error and lumbo-pelvic coordination during dynamic motion were assessed before and after 5 minutes WBV (18 Hz, 6 mm amplitude). Assessments were conducted before, immediately after, 30 minutes after and 1 hour after WBV. Subjects were found to have improved lumbo-pelvic coordination and flexibility without any adverse effect on the neuromuscular system after WBV. However, WBV had no significant immediate effect on lumbar repositioning ability and body alignment. Future studies of the effects of different WBV protocols on LBP patients are recommended.

  4. Are Children "Normal"?

    PubMed

    Black, Dan A; Kolesnikova, Natalia; Sanders, Seth G; Taylor, Lowell J

    2013-03-01

    We examine Becker's (1960) contention that children are "normal." For the cross section of non-Hispanic white married couples in the U.S., we show that when we restrict comparisons to similarly-educated women living in similarly-expensive locations, completed fertility is positively correlated with the husband's income. The empirical evidence is consistent with children being "normal." In an effort to show causal effects, we analyze the localized impact on fertility of the mid-1970s increase in world energy prices - an exogenous shock that substantially increased men's incomes in the Appalachian coal-mining region. Empirical evidence for that population indicates that fertility increases in men's income.

  5. Adverse Drug Reactions and quality deviations monitored by spontaneous reports

    PubMed Central

    Visacri, Marília Berlofa; de Souza, Cinthia Madeira; Sato, Catarina Miyako Shibata; Granja, Silvia; de Marialva, Mécia; Mazzola, Priscila Gava; Moriel, Patricia

    2014-01-01

    Objectives The aim of this study was to determine the frequency and profile of spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a Brazilian teaching hospital and propose a consistent classification to study quality deviations. Methods This is a descriptive and retrospective study involving the analysis of spontaneous reports of ADRs and quality deviations in 2010. ADRs were classified according to the reaction mechanism, severity, and causality. The drugs were classified according to their therapeutic classes and symptoms according to the affected organ. The quality deviations were classified according to the type of deviation and type of medicine available in the Brazilian market. Results A total of 68 forms were examined; ADRs accounted for 39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was the most affected organ, while anti-infectives (40.7%) were the therapeutic class that caused the most ADRs. The most common ADRs were type B (74.0%), moderates (37.0%), and probables (55.6%). In relation to quality deviations, the most frequent notifications were breaks, splits and leaks (20.9%) and related to generic drugs (43.9%). Conclusion The classification system to study quality deviations was clear and consistent. This study demonstrated that practices and public policies related to more effective pharmacovigilance need to be implemented so that the number of spontaneous reports increases. PMID:25972731

  6. Epigenetic programming of neurodegenerative diseases by an adverse environment.

    PubMed

    Babenko, Olena; Kovalchuk, Igor; Metz, Gerlinde A

    2012-03-20

    Experience and environment can critically influence the risk and progression of neurodegenerative disorders. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications, readily respond to experience and environmental factors. Here we propose that epigenetic regulation of gene expression and environmental modulation thereof may play a key role in the onset and course of common neurological conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. For example, epigenetic mechanisms may mediate long-term responses to adverse experience, such as stress, to affect disease susceptibility and the course of neurodegenerative events. This review introduces the epigenetic components and their possible role in mediating neuropathological processes in response to stress. We argue that epigenetic modifications will affect neurodegenerative events through altered gene function. The study of epigenetic states in neurodegenerative diseases presents an opportunity to gain new insights into risk factors and pathogenic mechanisms. Moreover, research into epigenetic regulation of disease may revolutionize health care by opening new avenues of personalized, preventive and curative medicine.

  7. Adverse reactions triggered by dental local anesthetics: a clinical survey.

    PubMed Central

    Kaufman, E.; Goharian, S.; Katz, Y.

    2000-01-01

    One hundred and seventy-nine patients completed a questionnaire focusing on adverse reactions to dental local anesthetics as manifested by 16 signs and symptoms. Twenty-six percent of the participants reported having at least 1 adverse reaction. It was found that most of the adverse reactions occurred within the first 2 hours following the injection of local anesthetics. Pallor, palpitations, diaphoresis, and dizziness were the most common adverse reactions reported in the study. The results pointed to a significant relationship between anxiety, gender, injection technique, and procedure with a higher incidence of adverse reactions. PMID:11432179

  8. 7 CFR 760.4 - Normal marketings of milk.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Normal marketings of milk. 760.4 Section 760.4... Farmers for Milk § 760.4 Normal marketings of milk. (a) The county committee shall determine the affected farmer's normal marketings which, for the purposes of this subpart, shall be the sum of the quantities...

  9. 7 CFR 760.4 - Normal marketings of milk.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Normal marketings of milk. 760.4 Section 760.4... Farmers for Milk § 760.4 Normal marketings of milk. (a) The county committee shall determine the affected farmer's normal marketings which, for the purposes of this subpart, shall be the sum of the quantities...

  10. 7 CFR 760.4 - Normal marketings of milk.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Normal marketings of milk. 760.4 Section 760.4... Farmers for Milk § 760.4 Normal marketings of milk. (a) The county committee shall determine the affected farmer's normal marketings which, for the purposes of this subpart, shall be the sum of the quantities...

  11. 7 CFR 760.4 - Normal marketings of milk.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Normal marketings of milk. 760.4 Section 760.4... Farmers for Milk § 760.4 Normal marketings of milk. (a) The county committee shall determine the affected farmer's normal marketings which, for the purposes of this subpart, shall be the sum of the quantities...

  12. 7 CFR 760.4 - Normal marketings of milk.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Normal marketings of milk. 760.4 Section 760.4... Farmers for Milk § 760.4 Normal marketings of milk. (a) The county committee shall determine the affected farmer's normal marketings which, for the purposes of this subpart, shall be the sum of the quantities...

  13. A prospective study of adverse drug reactions in hospitalized children

    PubMed Central

    Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J

    1999-01-01

    Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547

  14. [Usefulness and adverse effects of intrathecal metrizamide instillation (author's transl)].

    PubMed

    Masuzawa, H; Shimizu, H; Sano, K

    1979-08-01

    Radiographic quality as well as adverse effects of intrathecal metrizamide instillation was prospectively investigated in thirty-three clinical cases admitted to the department of neurosurgery, University of Tokyo Hospital, and Kantoh Teishin Hospital. Metrizamide CT cisternography was performed in fifteen cases using in most cases 10 ml of 170 mg I/ml solution through lumbar route. Eleven cases exhibited "normal" pattern CSF circulation and the remaining four, "delayed" pattern. Eight cases (53%) experienced headache, nausea, and/or vomiting several hours after the instillation. All of these belong to the "normal" pattern group. Four cases of "normal" pattern received electroencephalographic examinations before and after metrizamide instillation. Three revealed appearance of negative spike and slow wave burst or sharp waves one to twenty-four hours after the instillation, along with penetration of metrizamide into brain parenchyma. Diagnostic quality was interpreted as "good" in eleven cases. Small acoustic neurinoma, pituitary adenoma, arachnoid cyst, and subdural hygroma were diagnosed among others. Metrizamide ventriculography was done in four cases. No untoward effect of significance was attributed to metrizamide per se. Cervical myelograpy and/or CT myelography was done in fourteen cases using, in most cases, 10 ml of metrizamide 170 mgI/ml. Polytome tomography with metrizamide instillation through lateral cervical puncture was highly diagnostic, whereas, ordinary X-ray with lumbar instillation yielded less satisfactory results. CT myelography in cases of subarachnoid block required good consideration on instillation site and positioning of the patient. Six cases (50%) among twelve cases where metrizamide had run into the cranial cavity experienced headache, nausea, and/or vomiting to a lesser degree than those of cisterno graphy. Metrizamide is the first contrast agent ever made which can be safely introduced into human subarachnoid space, if administered

  15. Normal pressure hydrocephalus (NPH)

    MedlinePlus

    ... cerebrospinal fluid (CSF) in the brain that affects brain function. However, the pressure of the fluid is usually ... shunt that does not work well) Loss of brain function ( dementia ) that becomes worse over time Injury from ...

  16. Normals to a Parabola

    ERIC Educational Resources Information Center

    Srinivasan, V. K.

    2013-01-01

    Given a parabola in the standard form y[superscript 2] = 4ax, corresponding to three points on the parabola, such that the normals at these three points P, Q, R concur at a point M = (h, k), the equation of the circumscribing circle through the three points P, Q, and R provides a tremendous opportunity to illustrate "The Art of Algebraic…

  17. Cumulative early life adversity predicts longevity in wild baboons

    PubMed Central

    Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

  18. Cumulative early life adversity predicts longevity in wild baboons.

    PubMed

    Tung, Jenny; Archie, Elizabeth A; Altmann, Jeanne; Alberts, Susan C

    2016-04-19

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations.

  19. Exposures of children to organophosphate pesticides and their potential adverse health effects.

    PubMed Central

    Eskenazi, B; Bradman, A; Castorina, R

    1999-01-01

    Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children

  20. Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength.

    PubMed

    Lim, S V; Marenzana, M; Hopkinson, M; List, E O; Kopchick, J J; Pereira, M; Javaheri, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

    2015-04-01

    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites.

  1. Statokinesigram normalization method.

    PubMed

    de Oliveira, José Magalhães

    2017-02-01

    Stabilometry is a technique that aims to study the body sway of human subjects, employing a force platform. The signal obtained from this technique refers to the position of the foot base ground-reaction vector, known as the center of pressure (CoP). The parameters calculated from the signal are used to quantify the displacement of the CoP over time; there is a large variability, both between and within subjects, which prevents the definition of normative values. The intersubject variability is related to differences between subjects in terms of their anthropometry, in conjunction with their muscle activation patterns (biomechanics); and the intrasubject variability can be caused by a learning effect or fatigue. Age and foot placement on the platform are also known to influence variability. Normalization is the main method used to decrease this variability and to bring distributions of adjusted values into alignment. In 1996, O'Malley proposed three normalization techniques to eliminate the effect of age and anthropometric factors from temporal-distance parameters of gait. These techniques were adopted to normalize the stabilometric signal by some authors. This paper proposes a new method of normalization of stabilometric signals to be applied in balance studies. The method was applied to a data set collected in a previous study, and the results of normalized and nonnormalized signals were compared. The results showed that the new method, if used in a well-designed experiment, can eliminate undesirable correlations between the analyzed parameters and the subjects' characteristics and show only the experimental conditions' effects.

  2. Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011

    PubMed Central

    Nordanger, Dag Ø.; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

    2014-01-01

    Background Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care. PMID:24872862

  3. Future Directions in Childhood Adversity and Youth Psychopathology.

    PubMed

    McLaughlin, Katie A

    2016-01-01

    Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology-and whether those mechanisms are general or specific to particular kinds of adversity-remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children's development.

  4. Characterization of currently marketed heparin products: adverse event relevant bioassays.

    PubMed

    Sommers, Cynthia D; Montpas, Nicolas; Adam, Albert; Keire, David A

    2012-01-01

    The polyanion oversulfated chondroitin sulfate (OSCS) was identified as a contaminant in heparin products and was associated with severe hypotensive responses and other symptoms in patients receiving the drug. The OSCS associated adverse reactions were attributed to activation of the contact system via the plasma mediator, activated factor XII (FXIIa), which triggers kallikrein (KK) activity. Unlike heparin alone, OSCS, is able to activate FXII in plasma and stably bind to FXIIa enhancing plasma KK activity and the induction of vasoactive mediators such as bradykinin (BK), C3a and C5a. Similarly OSCS can interfere with heparin neutralization by the polycationic drug protamine. Here, we assess heparin (heparin sodium, dalteparin, tinzaparin or enoxaparin)-protamine complex formation and plasma based bioassays of KK, BK and C5a in a 96-well plate format. We establish the normal range of variation in the optimized bioassays across multiple lots from 9 manufacturers. In addition, because other oversulfated (OS) glycosaminoglycans (GAGs) besides OSCS could also serve as possible economically motivated adulterants (EMAs) to heparin, we characterize OS-dermatan sulfate (OSDS), OS-heparan sulfate (OSHS) and their native forms in the same assays. For the protamine test, OS-GAGs could be distinguished from heparin. For the KK assay, OSCS and OSDS were most potent followed by OSHS, and all had similar efficacies. Finally, OSDS had a greater efficacy in the C5a and BK assays followed by OSCS then OSHS. These data established the normal range of response of heparin products in these assays and the alteration in the responses in the presence of possible EMAs.

  5. Cutaneous adverse events in multiple sclerosis patients treated with daclizumab

    PubMed Central

    Cortese, Irene; Ohayon, Joan; Fenton, Kaylan; Lee, Chyi-Chia; Raffeld, Mark; Cowen, Edward W.; DiGiovanna, John J.

    2016-01-01

    Objective: To analyze the spectrum and mechanisms of cutaneous adverse events (AEs) in patients with multiple sclerosis treated with daclizumab high-yield process (DAC-HYP). Methods: A total of 31 participants in an institutional review board–approved open-label phase I study of DAC-HYP (NCT01143441) were prospectively evaluated over 42 months for development of cutaneous AEs. Participants provided written informed consent. Fifteen participants were naive to anti-CD25 therapy (cohort B), while 16 had received daclizumab (Zenapax; Hoffmann-La Roche) IV for 4–9 years (mean 5.8 years) prior to enrollment (cohort A). Immunohistochemistry was performed on pretreatment and posttreatment skin biopsies of normal-appearing skin (cohort B only) and on lesional biopsies in participants presenting with rash (both cohorts). Results: Cutaneous AEs occurred in 77% of patients, the majority presenting with patches of eczema requiring no treatment. Moderate to severe rash developed in 6 participants (19%) and required discontinuation of DAC-HYP in 4 (13%). More severe rashes presented psoriasiform phenotype, but lesional biopsies lacked features of either psoriasis or drug hypersensitivity eruptions. Instead, irrespective of clinical severity, lesional biopsies showed nonspecific features of eczematous dermatitis, but with prominent CD56+ lymphocytic infiltrates. Pretreatment and posttreatment biopsies of normal-appearing skin demonstrated no histopathologic changes. Conclusions: Observed cutaneous AEs are likely related to the immunomodulatory effects DAC-HYP exerts on innate lymphoid cells, including natural killer cells. Vigilance and timely management of skin reactions may prevent treatment discontinuation in participants with severe rash. PMID:26843560

  6. Population Analysis of Adverse Events in Different Age Groups Using Big Clinical Trials Data

    PubMed Central

    Eldredge, Christina; Cho, Chi C; Cisler, Ron A

    2016-01-01

    Background Understanding adverse event patterns in clinical studies across populations is important for patient safety and protection in clinical trials as well as for developing appropriate drug therapies, procedures, and treatment plans. Objectives The objective of our study was to conduct a data-driven population-based analysis to estimate the incidence, diversity, and association patterns of adverse events by age of the clinical trials patients and participants. Methods Two aspects of adverse event patterns were measured: (1) the adverse event incidence rate in each of the patient age groups and (2) the diversity of adverse events defined as distinct types of adverse events categorized by organ system. Statistical analysis was done on the summarized clinical trial data. The incident rate and diversity level in each of the age groups were compared with the lowest group (reference group) using t tests. Cohort data was obtained from ClinicalTrials.gov, and 186,339 clinical studies were analyzed; data were extracted from the 17,853 clinical trials that reported clinical outcomes. The total number of clinical trial participants was 6,808,619, and total number of participants affected by adverse events in these trials was 1,840,432. The trial participants were divided into eight different age groups to support cross-age group comparison. Results In general, children and older patients are more susceptible to adverse events in clinical trial studies. Using the lowest incidence age group as the reference group (20-29 years), the incidence rate of the 0-9 years-old group was 31.41%, approximately 1.51 times higher (P=.04) than the young adult group (20-29 years) at 20.76%. The second-highest group is the 50-59 years-old group with an incidence rate of 30.09%, significantly higher (P<.001) when compared with the lowest incidence in the 20-29 years-old group. The adverse event diversity also increased with increase in patient age. Clinical studies that recruited older

  7. Impact of childhood adversities on the short-term course of illness in psychotic spectrum disorders.

    PubMed

    Schalinski, Inga; Fischer, Yolanda; Rockstroh, Brigitte

    2015-08-30

    Accumulating evidence indicates an impact of childhood adversities on the severity and course of mental disorders, whereas this impact on psychotic disorders remains to be specified. Effects of childhood adversities on comorbidity, on symptom severity of the Positive and Negative Syndrome Scale and global functioning across four months (upon admission, 1 and 4 months after initial assessment), as well as the course of illness (measured by the remission rate, number of re-hospitalizations and dropout rate) were evaluated in 62 inpatients with psychotic spectrum disorders. Adverse experiences (of at least 1 type) were reported by 73% of patients. Patients with higher overall level of childhood adversities (n=33) exhibited more co-morbid disorders, especially alcohol/substance abuse and dependency, and higher dropout rates than patients with a lower levels of adverse experiences (n=29), together with higher levels of positive symptoms and symptoms of excitement and disorganization. Emotional and physical neglect were particularly related to symptom severity. Results suggest that psychological stress in childhood affects the symptom severity and, additionally, a more unfavorable course of disorder in patients diagnosed with psychoses. This impact calls for its consideration in diagnostic assessment and psychiatric care.

  8. Lycopersicon esculentum (Tomato) Prevents Adverse Effects of Lead on Blood Constituents

    PubMed Central

    SALAWU, Emmanuel O

    2010-01-01

    Background: Lead is known for its adverse effects on various organs and systems. In this study, the ability of lead to adversely affect blood parameters was investigated, and Lycopersicon esculentum, or commonly known as tomato (a source of antioxidants), was administered orally in the form of tomato paste (TP) to reduce the adverse effects of lead. Methods: The study involved 56 Wistar rats divided equally into 4 groups of 14 rats each: Control, LAG, TPG, and LA+TPG. Control and TPG rats were given distilled water ad libitum, while LAG and LA+TPG rats were given 1% lead (II) acetate (LA) per day. TPG and LA+TPG rats were additionally treated with 1.5 ml of TP per day. All treatments lasted for 10 weeks, after which the rats were weighed and sacrificed, and haematological and biochemical parameters were measured. The independent samples t test was used to analyse the results. Results: Lead caused significant reductions in the following parameters: weight; packed cell volume; red blood cell and white blood cell counts; the percentages of lymphocytes and monocytes; total serum protein, albumin, and globulin levels; and plasma superoxide dismutase and catalase activities. In contrast, lead caused a significant increase in the percentage of neutrophils and the plasma malondialdehyde concentration. TP, however, significantly prevented the adverse effects of LA. Conclusion: The oral administration of TP prevents the adverse effects of lead on blood constituents. PMID:22135544

  9. Depression among Black bisexual men with early and later life adversities.

    PubMed

    Allen, Vincent C; Myers, Hector F; Williams, John K

    2014-01-01

    This study examined the role of adulthood adversities in the relationship between childhood adversities and depression in 117 HIV-positive Black men who have sex with men and women (MSMW) and who have histories of childhood sexual abuse (CSA). Men were participants in the Enhanced Sexual Health Intervention for Men, a 6-session health intervention, and, at baseline, reported their experiences of CSA, childhood adversities, perceived discrimination, chronic stress, social support, and depressive symptoms. The relationship between childhood adversities, including CSA, and depression was mediated by experiences with racial and HIV discrimination, R² = .25, F(3, 112) = 12.67, p < .001, and chronic stress, R² = .17, F(3, 112) = 7.41, p < .001. Social support moderated the mediated effects of both racial and HIV discrimination, b = -.154, t(111) = -2.82, p < .01, and chronic stress, b = -.019, t(111) = -3.759, p < .01. Men's early adverse experiences were predictive of depression in adulthood; however, this relationship was largely affected by adulthood experiences, specifically discrimination, high chronic stress, and low social support. These findings illustrate pathways by which Black MSMW's early vulnerability for depression is either exacerbated or attenuated by their experiences as adults.

  10. Assessment of the expectancy, seriousness and severity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy

    PubMed Central

    Petrova, Guenka; Stoimenova, Assena; Dimitrova, Maria; Kamusheva, Maria; Petrova, Daniela; Georgiev, Ognian

    2017-01-01

    Introduction: Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. Methods: This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients. Prescribed medicines were systematized and national pharmacovigilance databases were searched for reported adverse drug reactions. The expectedness was evaluated through the review of the summary of product characteristics, the seriousness was evaluated by the clinicians based on the life threatening nature of the adverse drug reactions, and the severity was evaluated through Hartwig’s Severity Assessment Scale. Descriptive statistics of the reported adverse drug reactions was performed and the relative risk of developing an adverse drug reaction with all international non-proprietary names included in the analysis was calculated. Results: Results confirm that the chronic obstructive pulmonary disease is a disease with high appearance of adverse drug reactions, and causes many additional costs to the healthcare system. Unexpected and severe adverse drug reactions are frequent. A total of 4.8% of adverse drug reactions were evaluated as life threatening. Majority of adverse drug reactions are classified in Levels 1 (32.6%), 2 (26.4%) and 3 (19%) according to Hartwig’s Severity Assessment Scale. Approximately 22% of reported adverse drug reactions affect people’s everyday life to a greater extent and require additional therapy which might further increase the risk. The relative risk of developing an adverse drug reaction was highest for

  11. Adverse events after manual therapy among patients seeking care for neck and/or back pain: a randomized controlled trial

    PubMed Central

    2014-01-01

    : 1.77-3.52)) compared to men. Conclusion Adverse events after manual therapy are common and transient. Excluding spinal manipulation or stretching do not affect the occurrence of adverse events. The most common adverse event is soreness in the muscles. Women reports more adverse events than men. Trial registration This trial was registered in a public registry (Current Controlled Trials) (ISRCTN92249294). PMID:24618345

  12. Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion

    PubMed Central

    Stundner, O.; Chiu, Y-L.; Sun, X.; Ramachandran, S-K.; Gerner, P.; Vougioukas, V.; Mazumdar, M.; Memtsoudis, S. G.

    2014-01-01

    Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84 655 patients undergoing posterior lumbar fusion were identified and 7.28% also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood transfusion, and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (Odds Ratio (OR) 1.50, Confidence Interval (CI) 1.38;1.62), blood transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians. PMID:24493191

  13. Diabetes distress may adversely affect the eating styles of women with type 1 diabetes

    PubMed Central

    Quinn, Laurie; Hacker, Eileen; Park, Hanjong; Kujath, Amber S.

    2015-01-01

    The aim of this study was to determine the relationships among diabetes distress, fear of hypoglycemia, and eating styles in women with type 1 diabetes (T1DM). Fifteen women (mean age 37 ± 13.5 years) with T1DM completed surveys measuring diabetes distress, fear of hypoglycemia (FOH), and eating style. Height, weight, and A1C were obtained, and open-ended comments regarding hypoglycemic concerns and experiences were recorded. Diabetes distress was positively associated with A1C (r = .655, p = .008). High levels of external (73 %), emotional (47 %), and restrained (53 %) eating styles were reported. Emotional and external eating styles were positively associated with diabetes distress (r = .575 and r = .622; p <.05). Those with poorer glycemic control (A1C ≥ 7 %; 53 mmol/mol) had higher levels of restrained eating behavior (F = 10.69, p = .006) and greater interpersonal distress (F = 5.916, p = .03) than those with better glycemic control (A1C < 7 %; 53 mmol/mol). A nonlinear relationship was identified between interpersonal distress and FOH (behavior subscale, p = .0383) indicating that fewer behavioral approaches were employed to avoid hypoglycemia at higher distress levels. The women in this sample were emotionally burdened by their disease. Distress was associated with eating styles linked with overeating and poor glycemic control. High levels of emotional and external eating styles may have important clinical implications for those with T1DM. PMID:24615054

  14. Urban cultivation in allotments maintains soil qualities adversely affected by conventional agriculture

    PubMed Central

    Edmondson, Jill L; Davies, Zoe G; Gaston, Kevin J; Leake, Jonathan R

    2014-01-01

    Modern agriculture, in seeking to maximize yields to meet growing global food demand, has caused loss of soil organic carbon (SOC) and compaction, impairing critical regulating and supporting ecosystem services upon which humans also depend. Own-growing makes an important contribution to food security in urban areas globally, but its effects on soil qualities that underpin ecosystem service provision are currently unknown. We compared the main indicators of soil quality; SOC storage, total nitrogen (TN), C : N ratio and bulk density (BD) in urban allotments to soils from the surrounding agricultural region, and between the allotments and other urban greenspaces in a typical UK city. A questionnaire was used to investigate allotment management practices that influence soil properties. Allotment soils had 32% higher SOC concentrations and 36% higher C : N ratios than pastures and arable fields and 25% higher TN and 10% lower BD than arable soils. There was no significant difference between SOC concentration in allotments and urban non-domestic greenspaces, but it was higher in domestic gardens beneath woody vegetation. Allotment soil C : N ratio exceeded that in non-domestic greenspaces, but was lower than that in garden soil. Three-quarters of surveyed allotment plot holders added manure, 95% composted biomass on-site, and many added organic-based fertilizers and commercial composts. This may explain the maintenance of SOC, C : N ratios, TN and low BD, which are positively associated with soil functioning. Synthesis and applications. Maintenance and protection of the quality of our soil resource is essential for sustainable food production and for regulating and supporting ecosystem services upon which we depend. Our study establishes, for the first time, that small-scale urban food production can occur without the penalty of soil degradation seen in conventional agriculture, and maintains the high soil quality seen in urban greenspaces. Given the involvement of over 800 million people in urban agriculture globally, and its important contribution to food security, our findings suggest that to better protect soil functions, local, national and international urban planning and policy making should promote more urban own-growing in preference to further intensification of conventional agriculture to meet increasing food demand. PMID:25641978

  15. Prenatal zinc supplementation of zinc-adequate rats adversely affects immunity in offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that zinc (Zn) supplementation of Zn-adequate dams induced immunosuppressive effects that persist in the offspring after weaning. We investigated whether the immunosuppressive effects were due to in utero exposure and/or mediated via milk using a cross-fostering design. Pregnant...

  16. Children's health insurance program premiums adversely affect enrollment, especially among lower-income children.

    PubMed

    Abdus, Salam; Hudson, Julie; Hill, Steven C; Selden, Thomas M

    2014-08-01

    Both Medicaid and the Children's Health Insurance Program (CHIP), which are run by the states and funded by federal and state dollars, offer health insurance coverage for low-income children. Thirty-three states charged premiums for children at some income ranges in CHIP or Medicaid in 2013. Using data from the 1999-2010 Medical Expenditure Panel Surveys, we show that the relationship between premiums and coverage varies considerably by income level and by parental access to employer-sponsored insurance. Among children with family incomes above 150 percent of the federal poverty level, a $10 increase in monthly premiums is associated with a 1.6-percentage-point reduction in Medicaid or CHIP coverage. In this income range, the increase in uninsurance may be higher among those children whose parents lack an offer of employer-sponsored insurance than among those whose parents have such an offer. Among children with family incomes of 101-150 percent of poverty, a $10 increase in monthly premiums is associated with a 6.7-percentage-point reduction in Medicaid or CHIP coverage and a 3.3-percentage-point increase in uninsurance. In this income range, the increase in uninsurance is even larger among children whose parents lack offers of employer coverage.

  17. Cellular senescence induced by prolonged subculture adversely affects glutamate uptake in C6 lineage.

    PubMed

    Pereira, Mery Stéfani Leivas; Zenki, Kamila; Cavalheiro, Marcela Mendonça; Thomé, Chairini Cássia; Filippi-Chiela, Eduardo Cremonese; Lenz, Guido; de Souza, Diogo Onofre Gomes; de Oliveira, Diogo Losch

    2014-05-01

    Several researchers have recently used C6 cells to evaluate functional properties of high-affinity glutamate transporters. However, it has been demonstrated that this lineage suffers several morphological and biochemical alterations according to the number of passages in culture. Currently, there are no reports showing whether functional properties of high-affinity glutamate transporters comply with these sub culturing-dependent modifications. The present study aimed to compare the functional properties of high-affinity glutamate transporters expressed in early (EPC6) and late (LPC6) passage C6 cells through a detailed pharmacological and biochemical characterization. Between 60-180 min of L-[(3)H]glu incubation, LPC6 presented an intracellular [(3)H] 55% lower than EPC6. Both cultures showed a time-dependent increase of intracellular [(3)H] reaching maximal levels at 120 min. Cultures incubated with D-[(3)H]asp showed a time-dependent increase of [(3)H] until 180 min. Moreover, LPC6 have a D-[(3)H]asp-derived intracellular [(3)H] 30-45% lower than EPC6 until 120 min. Only EAAT3 was immunodetected in cultures and its total content was equal between them. PMA-stimulated EAAT3 trafficking to membrane increased 50% of L-[(3)H]glu-derived intracellular [(3)H] in EPC6 and had no effect in LPC6. LPC6 displayed characteristics that resemble senescence, such as high β-Gal staining, cell enlargement and increase of large and regular nuclei. Our results demonstrated that LPC6 exhibited glutamate uptake impairment, which may have occurred due to its inability to mobilize EAAT3 to cell membrane. This profile might be related to senescent process observed in this culture. Our results suggest that LPC6 cells are an inappropriate glial cellular model to investigate the functional properties of high-affinity glutamate transporters.

  18. To provide additional housing assistance for certain individuals and households adversely affected by a major disaster.

    THOMAS, 111th Congress

    Rep. Hinchey, Maurice D. [D-NY-22

    2009-06-26

    06/29/2009 Referred to the Subcommittee on Economic Development, Public Buildings and Emergency Management. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  19. Our Results-Driven, Testing Culture: How It Adversely Affects Students' Personal Experience

    ERIC Educational Resources Information Center

    Lesch, Lyn

    2007-01-01

    Author Lyn Lesch advocates that learning cannot be measured by empirical results like testing and grading. As the founder of Chicago's The Children's School, Lesch didn't give grades or submit students to standardized testing. Such conditions may seem blasphemous to most educators, but the results spoke for themselves. Without the high-stakes…

  20. Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring.

    PubMed

    Haghani, M; Shabani, M; Moazzami, K

    2013-10-10

    Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks.

  1. Urban-rural status affects associations between domains of environmental quality and adverse birth outcomes

    EPA Science Inventory

    The relationship between environmental conditions and human health varies by environmental domain and urbanicity. To account for multiple ambient environmental conditions, we constructed an Environmental Quality Index (EQI) for health research. We used U.S. county level data rep...

  2. Cognitive load imposed by ultrasound-facilitated teaching does not adversely affect gross anatomy learning outcomes.

    PubMed

    Jamniczky, Heather A; Cotton, Darrel; Paget, Michael; Ramji, Qahir; Lenz, Ryan; McLaughlin, Kevin; Coderre, Sylvain; Ma, Irene W Y

    2017-03-01

    Ultrasonography is increasingly used in medical education, but its impact on learning outcomes is unclear. Adding ultrasound may facilitate learning, but may also potentially overwhelm novice learners. Based upon the framework of cognitive load theory, this study seeks to evaluate the relationship between cognitive load associated with using ultrasound and learning outcomes. The use of ultrasound was hypothesized to facilitate learning in anatomy for 161 novice first-year medical students. Using linear regression analyses, the relationship between reported cognitive load on using ultrasound and learning outcomes as measured by anatomy laboratory examination scores four weeks after ultrasound-guided anatomy training was evaluated in consenting students. Second anatomy examination scores of students who were taught anatomy with ultrasound were compared with historical controls (those not taught with ultrasound). Ultrasound's perceived utility for learning was measured on a five-point scale. Cognitive load on using ultrasound was measured on a nine-point scale. Primary outcome was the laboratory examination score (60 questions). Learners found ultrasound useful for learning. Weighted factor score on "image interpretation" was negatively, but insignificantly, associated with examination scores [F (1,135) = 0.28, beta = -0.22; P = 0.61]. Weighted factor score on "basic knobology" was positively and insignificantly associated with scores; [F (1,138) = 0.27, beta = 0.42; P = 0.60]. Cohorts exposed to ultrasound had significantly higher scores than historical controls (82.4% ± SD 8.6% vs. 78.8% ± 8.5%, Cohen's d = 0.41, P < 0.001). Using ultrasound to teach anatomy does not negatively impact learning and may improve learning outcomes. Anat Sci Educ 10: 144-151. © 2016 American Association of Anatomists.

  3. Aggregation of adverse behaviors and its affecting factors among young military conscripts in Taiwan.

    PubMed

    Wu, Der-Min; Chu, Nain-Feng; Lin, Yaoh-Shiang; Lai, Hsiang-Ru

    2007-06-01

    The authors studied the prevalence of the aggregation in common lifestyle habits, namely, cigarette smoking, alcohol drinking, and betel-nut chewing and the demographic correlates of individual aggregation in these lifestyle behaviors among young military conscripts in Taiwan. Cross-sectional screening was conducted among conscripts in southern and eastern sections of Taiwan from Aug. 1st to Dec. 31st 2001. Totally, 3913 conscripts who had more than 1 month of service were included in this multistage sampling study. Information on smoking, drinking, and betel-nut chewing habits were ascertained as part of a self-administered questionnaire completed by examinees at the service unit. Aggregation in lifestyle habits was studied by comparing the observed and expected proportions (O/E ratio) with their 95% confidence intervals (CI) for zero, one, two, and three simultaneously occurring lifestyle habits. The study results showed a significant clustering of lifestyle habits studied; the number of subjects was greater than expected in groups with two (for cigarette smoking and betel-nut chewing, O/E ratio=1.17, 95%CI=1.06-1.28), and three (O/E ratio=5.63, 95%CI=5.06-6.20) lifestyle habits. Determinants for this clustering of lifestyle habits included lower educational levels and residential area in southern and eastern sections of Taiwan. There was a significant individual aggregation in lifestyle habits including cigarette smoking, alcohol drinking, and betel-nut chewing in the health survey among young military conscripts. In addition, young military conscripts with low educational levels and residential area in southern and eastern sections of Taiwan had an apparent tendency toward the aggregation in these lifestyle habits.

  4. Ageing Adversely Affects the Migration and Function of Marginal Zone B Cells.

    PubMed

    Turner, Vivian M; Mabbott, Neil A

    2017-04-02

    Marginal zone (MZ) B cells are positioned within the spleen to capture blood-borne Ag and immune complexes and deliver them to follicular dendritic cells in the B cell follicles. We show that within the spleens of aged mice antigen (Ag) capture by MZ B cells, and their ability to shuttle between the follicle and MZ were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine 1-phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T cell-independent (TI) antibody-responses to microbial polysaccharide Ag. In aged mice the ability to produce immunoglobulins in response to the TI-type 1 Ag, TNP-LPS, was impaired. These ageing related changes to the MZ and MZ B cells have implications for the clearance of blood-borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI Ag, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing-related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly. This article is protected by copyright. All rights reserved.

  5. Psychosocial problems of donor heart recipients adversely affecting quality of life.

    PubMed

    Bunzel, B; Wollenek, G; Grundböck, A

    1992-10-01

    Heart transplantation has become an accepted therapy for patients suffering from terminal heart disease for whom neither standard forms of medication nor the usual surgery are of any benefit. Although results regarding postoperative quantity and quality of life are encouraging, it must not be overlooked that the patient and his family face, and have to overcome, profound psychosocial problems. The main stressors were identified in interviews with 47 heart transplant patients. The main preoperative problems were: the way of being informed about the diagnosis, the waiting period for transplantation, anguishing doubts about the decision to have a transplant, being a body without heart ('zombie'), guilt and shame regarding the donor, the reactions of others. Postoperatively the patients have to cope with: re-entering social systems, reactions of friends, neighbours and colleagues, rejection episodes, death of a fellow patient, the need to redesign family life. All the problems reported by the patients interviewed are discussed regarding their psychosocial implications, and hints are given on how to minimize them.

  6. Navy Acquisition. SUBACS (Submarine Advanced Combat System) Problems May Adversely Affect Navy Attack Submarine Programs.

    DTIC Science & Technology

    1985-11-01

    also the combat system design for the proposed new attack submarine class, SSN 21. In December 1983, the Navy awarded the International Business Machines...VI: Comments From International Business 35 Machines Corporation Abbreviations DNSARC Department of the Navy Systems Acquisition Review Council DSARC...Defense Systems Acquisition Review Council GAO General Accounting Office IBM International Business Machines Corporation NAVsEA Naval Sea Systems

  7. Urban cultivation in allotments maintains soil qualities adversely affected by conventional agriculture.

    PubMed

    Edmondson, Jill L; Davies, Zoe G; Gaston, Kevin J; Leake, Jonathan R

    2014-08-01

    Modern agriculture, in seeking to maximize yields to meet growing global food demand, has caused loss of soil organic carbon (SOC) and compaction, impairing critical regulating and supporting ecosystem services upon which humans also depend. Own-growing makes an important contribution to food security in urban areas globally, but its effects on soil qualities that underpin ecosystem service provision are currently unknown. We compared the main indicators of soil quality; SOC storage, total nitrogen (TN), C : N ratio and bulk density (BD) in urban allotments to soils from the surrounding agricultural region, and between the allotments and other urban greenspaces in a typical UK city. A questionnaire was used to investigate allotment management practices that influence soil properties. Allotment soils had 32% higher SOC concentrations and 36% higher C : N ratios than pastures and arable fields and 25% higher TN and 10% lower BD than arable soils. There was no significant difference between SOC concentration in allotments and urban non-domestic greenspaces, but it was higher in domestic gardens beneath woody vegetation. Allotment soil C : N ratio exceeded that in non-domestic greenspaces, but was lower than that in garden soil. Three-quarters of surveyed allotment plot holders added manure, 95% composted biomass on-site, and many added organic-based fertilizers and commercial composts. This may explain the maintenance of SOC, C : N ratios, TN and low BD, which are positively associated with soil functioning. Synthesis and applications. Maintenance and protection of the quality of our soil resource is essential for sustainable food production and for regulating and supporting ecosystem services upon which we depend. Our study establishes, for the first time, that small-scale urban food production can occur without the penalty of soil degradation seen in conventional agriculture, and maintains the high soil quality seen in urban greenspaces. Given the involvement of over 800 million people in urban agriculture globally, and its important contribution to food security, our findings suggest that to better protect soil functions, local, national and international urban planning and policy making should promote more urban own-growing in preference to further intensification of conventional agriculture to meet increasing food demand.

  8. Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis.

    PubMed

    Chandrashekar, Preeti; Manickam, Ravikumar; Ge, Xiaojia; Bonala, Sabeera; McFarlane, Craig; Sharma, Mridula; Wahli, Walter; Kambadur, Ravi

    2015-07-15

    Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, our laboratory showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that PPARβ/δ modulates myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPARβ/δ-null mice display reduced body weight, skeletal muscle weight, and myofiber atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPARβ/δ-null mice, suggesting a role for PPARβ/δ in muscle regeneration. To investigate this, tibialis anterior muscles were injured with notexin, and muscle regeneration was monitored on days 3, 5, 7, and 28 postinjury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPARβ/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPARβ/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced before injury, satellite cell self-renewal was found to be unaffected in PPARβ/δ-null mice after regeneration. Previously, our laboratory had showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that inactivation of PPARβ/δ increases myostatin signaling and inhibits myogenesis. Our results here indeed confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated tibialis anterior muscle from PPARβ/δ-null mice. Taken together, these data suggest that absence of PPARβ/δ leads to loss of satellite cells, impaired skeletal muscle regeneration, and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.

  9. Mexico City air pollution adversely affects olfactory function and intranasal trigeminal sensitivity.

    PubMed

    Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn

    2009-11-01

    Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.

  10. The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

    PubMed Central

    Kundakovic, Marija; Jaric, Ivana

    2017-01-01

    Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

  11. Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

    PubMed Central

    Brennan-Speranza, Tara C.; Henneicke, Holger; Gasparini, Sylvia J.; Blankenstein, Katharina I.; Heinevetter, Uta; Cogger, Victoria C.; Svistounov, Dmitri; Zhang, Yaqing; Cooney, Gregory J.; Buttgereit, Frank; Dunstan, Colin R.; Gundberg, Caren; Zhou, Hong; Seibel, Markus J.

    2012-01-01

    Long-term glucocorticoid treatment is associated with numerous adverse outcomes, including weight gain, insulin resistance, and diabetes; however, the pathogenesis of these side effects remains obscure. Glucocorticoids also suppress osteoblast function, including osteocalcin synthesis. Osteocalcin is an osteoblast-specific peptide that is reported to be involved in normal murine fuel metabolism. We now demonstrate that osteoblasts play a pivotal role in the pathogenesis of glucocorticoid-induced dysmetabolism. Osteoblast-targeted disruption of glucocorticoid signaling significantly attenuated the suppression of osteocalcin synthesis and prevented the development of insulin resistance, glucose intolerance, and abnormal weight gain in corticosterone-treated mice. Nearly identical effects were observed in glucocorticoid-treated animals following heterotopic (hepatic) expression of both carboxylated and uncarboxylated osteocalcin through gene therapy, which additionally led to a reduction in hepatic lipid deposition and improved phosphorylation of the insulin receptor. These data suggest that the effects of exogenous high-dose glucocorticoids on insulin target tissues and systemic energy metabolism are mediated, at least in part, through the skeleton. PMID:23093779

  12. Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

    PubMed

    Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

    2014-06-01

    3A4, 2C9 and 2C19 are common in our patients with statin induced adverse effects. Normalizing the thyroid hormone status and optimizing of the concomitant medication may reduce the risk of statin induced adverse effects.

  13. Peripartum cocaine use and adverse pregnancy outcome.

    PubMed

    Little, Bertis B.; Snell, Laura M.; Trimmer, Kenneth J.; Ramin, Susan M.; Ghali, Fred; Blakely, Craig A.; Garret, Andrea

    1999-09-01

    The objective of the study was to analyze possible adverse effects of peripartum cocaine use on maternal and fetal outcomes. Informed consent was given by 720 (97%) of 740 women who delivered consecutively at a large urban public hospital to test an umbilical cord blood sample for the presence of non-medically administered drugs of abuse and alcohol and to be interviewed for the study. Samples were tested for the presence of a cocaine metabolite (benzoylecgonine-BZE) by radioimmunoassay. The presence of other substances of abuse (alcohol, methamphetamine, opiates) resulted in exclusion from the sample of 143 subjects. Thus, in this cohort analysis, drug-free controls (N = 469) were compared to those positive for cocaine only (N = 108). Peripartum exposure to cocaine only, and no other substances of abuse, was associated with an increased frequency of abruptio placentae (1.9% vs 0% for control, P < 0.004), thick meconium stained amniotic fluid (3.9% vs 0.7% for controls, P < 0.006), premature rupture of membranes (P < 0.02), genitourinary anomalies (OR = 3.6, P < 0.05), abdominal wall defects (OR = 4.4, P < 0.01) and increased frequency of low birth weight (OR = 2.0, P < 0.02). These are important findings because previous studies have been complicated by the confounding effects of other substances of abuse. Am. J. Hum. Biol. 11:598-602, 1999. Copyright 1999 Wiley-Liss, Inc.

  14. Constructing Adverse Outcome Pathways: a Demonstration of ...

    EPA Pesticide Factsheets

    Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating events (MIEs) of chemicals to their downstream phenotypes of a greater regulatory relevance. A number of ongoing public phenomics (high throughput phenotyping) efforts have been generating abundant phenotypic data annotated with ontology terms. These phenotypes can be analyzed semantically and linked to MIEs of interest, all in the context of a knowledge base integrated from a variety of ontologies for various species and knowledge domains. In such analyses, two phenotypic profiles (PPs; anchored by genes or diseases) each characterized by multiple ontology terms are compared for their semantic similarities within a common ontology graph, but across boundaries of species and knowledge domains. Taking advantage of publicly available ontologies and software tool kits, we have implemented an OS-Mapping (Ontology-based Semantics Mapping) approach as a Java application, and constructed a network of 19383 PPs as nodes with edges weighed by their pairwise semantic similarity scores. Individual PPs were assembled from public phenomics data. Out of possible 1.87×108 pairwise connections among these nodes, about 71% of them have similarity scores between 0.2 and the maximum possible of 1.0.

  15. Adapting biomarker technologies to adverse outcome ...

    EPA Pesticide Factsheets

    Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, there are now new technologies being considered derived from the broad field of breath research, especially in applications of gas-phase analysis and instrumentation. The ultimate goal is to discover disease progressions in human or animal systems, identify them at the molecular or cellular level, and then choose analytes that can distinctly define the presence of a particular path (Ankley et al. 2010, Villeneuve et al. 2014). Once such in vivo pathways are identified, then in vitro assays can be developed for streamlined testing of chemical effects without additional human or animal based studies (Pleil et al. 2012). Recent work has focused on discovery analysis in breath, or other biological media, wherein as many as possible compounds are cataloged and then linked to their biochemical source as exogenous (external), endogenous (internal) or from the microbiome (Pleil et al. 2013a, de Lacy Costello 2014, Pleil et al. 2013b, Trefz et al. 2013, Pleil et al. 2014). Such research lays the groundwork for identifying compounds from systems biology that might be relevant for developing AOPs for in vitro research. The National Exposure Research Laboratory’s (NERL’s) Human Exposure and Atm

  16. [Management of adverse effects with antituberculosis chemotherapy].

    PubMed

    Tsuyuguchi, Kazunari; Wada, Masako

    2011-02-01

    Tuberculosis has now become a curable disease with chemotherapy. So it is natural that the present issues in tuberculosis management are focused on how to complete standard chemotherapy. In this context, management of adverse effects constitutes an essential part of antituberculosis chemotherapy, as well as directly observed therapy. In this symposium, discussions were held about three major subjects on this issue. First, hepatotoxicity develops frequently and has sometimes fatal outcome, which makes it the most problematic adverse effect. "Management of hepatotoxicity during antituberculosis chemotherapy" was published by the Japanese Society for Tuberculosis (JST) in 2006. Dr. Shinsho Yoshiba evaluated this recommendation and pointed out that the criteria for discontinuation of drug based on AST, ALT and bilirubin levels is too sensitive and the concept of predicting fulminant hepatic failure (FHF) is lacking. He stressed the importance of monitoring serum prothrombin time for predicting FHF. Next, allergic drug reaction such as fever or skin rash often causes distress, although rarely fatal. As isoniazid (INH) and rifampicin (RFP) are key drugs for the cure, readministration of these drugs is often attempted by desensitization therapy. "Recommendation about desensitization therapy of antituberculosis drugs" was also published by JST in 1997. Dr. Yoshihiro Kobashi reported high success rates of 79 percent for INH and 75 percent for RFP according to this recommendation. He also reported correlated factor with the success, such as the longer period from the discontinuation to the desensitization therapy and lower doses of drugs at starting desensitization. Finally, we sometimes experience transient worsening of radiographical findings and general symptoms during antituberculosis chemotherapy. This is presumed to be due to allergic reaction to dead bacilli without requiring discontinuation of the drug. Differential diagnosis includes drug-induced pneumonia requring

  17. Adverse health consequences of the Vietnam War.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2015-01-01

    The 40th anniversary of the end of the Vietnam War is a useful time to review the adverse health consequences of that war and to identify and address serious problems related to armed conflict, such as the protection of noncombatant civilians. More than 58,000 U.S. servicemembers died during the war and more than 150,000 were wounded. Many suffered from posttraumatic stress disorders and other mental disorders and from the long-term consequences of physical injuries. However, morbidity and mortality, although difficult to determine precisely, was substantially higher among the Vietnamese people, with at least two million of them dying during the course of the war. In addition, more than one million Vietnamese were forced to migrate during the war and its aftermath, including many "boat people" who died at sea during attempts to flee. Wars continue to kill and injure large numbers of noncombatant civilians and continue to damage the health-supporting infrastructure of society, expose civilians to toxic chemicals, forcibly displace many people, and divert resources away from services to benefit noncombatant civilians. Health professionals can play important roles in promoting the protection of noncombatant civilians during war and helping to prevent war and create a culture of peace.

  18. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  19. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

    Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

  20. Analyzing risks of adverse pregnancy outcomes.

    PubMed

    Kramer, Michael S; Zhang, Xun; Platt, Robert W

    2014-02-01

    Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

  1. Reporting vaccine-associated adverse events.

    PubMed Central

    Duclos, P.; Hockin, J.; Pless, R.; Lawlor, B.

    1997-01-01

    OBJECTIVE: To determine family physicians' awareness of the need to monitor and report vaccine-associated adverse events (VAAE) in Canada and to identify mechanisms that could facilitate reporting. DESIGN: Mailed survey. SETTING: Canadian family practices. PARTICIPANTS: Random sample of 747 family physicians. Overall response rate was 32% (226 of 717 eligible physicians). MAIN OUTCOME MEASURES: Access to education on VAAE; knowledge about VAAE monitoring systems, reporting criteria, and reporting forms; method of reporting VAAEs and reasons for not reporting them; and current experience with VAAEs. RESULTS: Of 226 respondents, 55% reported observing VAAEs, and 42% reported the event. Fewer than 50% were aware of a monitoring system for VAAE, and only 39% had had VAAE-related education during medical training. Only 28% knew the reporting criteria. Reporting was significantly associated with knowledge of VAAE monitoring systems and reporting criteria (P < 0.01). CONCLUSION: Physicians need more feedback and education on VAAE reporting and more information about the importance of reporting and about reporting criteria and methods. PMID:9303234

  2. Chapter 1: Direct Normal Radiation

    SciTech Connect

    Myer, Daryl R.

    2016-04-15

    This chapter addresses the quantitative and qualitative aspects of the solar resource, the direct solar radiation. It discusses the total or integrated broadband direct beam extraterrestrial radiation (ETR). This total integrated irradiance is comprised of photons of electromagnetic radiation. The chapter also discusses the impact of the atmosphere and its effect upon the direct normal irradiance (DNI) beam radiation. The gases and particulates present in the atmosphere traversed by the direct beam reflect, absorb, and scatter differing spectral regions and proportions of the direct beam, and act as a variable filter. Knowledge of the available broadband DNI beam radiation resource data is essential in designing a concentrating photovoltaic (CPV) system. Spectral variations in the DNI beam radiation affect the performance of a CPV system depending on the solar cell technology used. The chapter describes propagation and scattering processes of circumsolar radiation (CSR), which includes the Mie scattering from large particles.

  3. Effect of lithium on plasma glucose, insulin and glucagon in normal and streptozotocin-diabetic rats: role of glucagon in the hyperglycaemic response.

    PubMed Central

    Hermida, O. G.; Fontela, T.; Ghiglione, M.; Uttenthal, L. O.

    1994-01-01

    1. Lithium salts, used in the treatment of affective disorders, may have adverse effects on glucose tolerance in man, and suppress glucose-stimulated insulin secretion in rats. 2. To study the interaction of these effects with pre-existing diabetes mellitus, plasma glucose and insulin responses to lithium chloride were measured in male Wistar rats made diabetic with intraperitoneal streptozotocin, and in normal controls. 3. In both normal and diabetic anaesthetized rats, intravenous lithium (4 mEq kg-1) caused a rise in plasma glucose. In absolute terms, the rise was greater in diabetic (5.2 mmol l-1) than in normal rats (2.3 mmol l-1). 4. Plasma insulin concentrations were reduced by lithium in normal rats, but the low insulin concentrations measured in the diabetic rats were not significantly changed. 5. After intravenous glucose (0.5 g kg-1), lithium-treated diabetic rats showed a second rise in plasma glucose at 60-90 min without any insulin response, while normal rats showed typically reduced insulin responses and initial glucose disappearance rates. 6. Intravenous glucose reduced plasma glucagon concentrations to a greater extent in normal than in diabetic rats, but lithium induced an equal rise in plasma glucagon in both groups, with a time-course similar to that of the hyperglycaemic effect. 7. The hyperglycaemic action of lithium is greater in the hypoinsulinaemic diabetic rats and appears to involve a stimulation of glucagon secretion in both normal and diabetic animals. PMID:8019763

  4. Adverse effects of stress on microbiota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complex communities of microorganisms that colonize the gastrointestinal tract impact the health status of an animal. The health of an animal as well as production traits are also affected by exposure to stress. The aim of present study was to evaluate the effects of dehorning stress on the gut ...

  5. An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses.

    PubMed

    Witt, Stephanie H; Buchmann, Arlette F; Blomeyer, Dorothea; Nieratschker, Vanessa; Treutlein, Jens; Esser, Günter; Schmidt, Martin H; Bidlingmaier, Martin; Wiedemann, Klaus; Rietschel, Marcella; Laucht, Manfred; Wüst, Stefan; Zimmermann, Ulrich S

    2011-08-01

    Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene-environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.

  6. Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

    Nassar, Basant R.; Lippa, Carol F.

    2016-01-01

    Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” “gait disturbances,” “cognitive function,” “neuropsychology,” “imaging,” and “pathogenesis,” articles were obtained for this review. The majority of the articles were retrieved from the past 10 years. The purpose of this review article is to aid general practitioners in further understanding current findings on the pathogenesis, diagnosis, and treatment of iNPH. PMID:28138494

  7. Studies of normal hearing.

    PubMed

    Catlin, F I

    1984-01-01

    Auditory function changes continually from birth to old age. A variety of methods to assess hearing have evolved since the invention of the audiometer. Types of measurement include: electrical response in the central nervous system, cochlear acuity and speech responses. While some of these tests correlate fairly well with each other, their ability to represent overall hearing function is questionable. Other attempts to improve the assessment of hearing have been made in the area of self-appraisal, but these, too, have significant limitations. Most self-report and peer appraisal questionnaires have been established by studies of hearing-impaired populations. Norms for these techniques in normal-hearing populations need to be established. There is still room for valid tests of everyday communication. What we have in measurement procedures does not achieve this goal. Research studies of today will hopefully produce better definition of normal auditory function.

  8. Normal-reflection image

    SciTech Connect

    Huang, L.; Fehler, Michael C.

    2003-01-01

    Common-angle wave-equation migration using the double-square-root is generally less accurate than the common-shot migration because the wavefield continuation equation for thc former involves additional approximations compared to that for the latter. We present a common-angle wave-equation migration that has the same accuracy as common-shot wave-equation migration. An image obtained from common-angle migration is a four- to five-dimensional output volume for 3D cases. We propose a normal-reflection imaging condition for common-angle migration to produce a 3D output volume for 3D migration. The image is closely related to the normal-reflection coefficients at interfaces. This imaging condition will allow amplitude-preserving migration to generate an image with clear physical meaning.

  9. [Normal bone marrow and common reactive alterations].

    PubMed

    Tzankov, A; Dirnhofer, S; Beham-Schmid, C

    2012-11-01

    Histological examination of bone marrow biopsies is an important and powerful diagnostic tool to assess various hematological and non-hematological disorders. Morphological examination of such biopsies requires knowledge of the composition of normal bone marrow and its variations, such as age-related changes. Diagnostic problems may arise due to poor specimen quality, insufficient sections or stainings and insufficient experience with reactive bone marrow changes which occasionally resemble neoplastic disorders. Reactive bone marrow processes can affect one or more hematopoietic cell lines, lead to disruption of the normal architecture and specifically affect the bone marrow stroma. Optimal bone marrow diagnosis requires adequately stained slides and, when needed, immunophenotyping and molecular examinations. Furthermore, rather than biopsy interpretation of other organs, pathologists routinely need clinical history information for correct interpretation and diagnosis of bone marrow changes. In this article, the normal features of bone marrow as well as the most frequent reactive bone marrow alterations are described.

  10. [Affective dependency].

    PubMed

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  11. Childhood adversity impacts on brain subcortical structures relevant to depression.

    PubMed

    Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J

    2017-03-01

    Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression.

  12. Future Directions in Childhood Adversity and Youth Psychopathology

    PubMed Central

    McLaughlin, Katie A.

    2016-01-01

    Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology—and whether those mechanisms are general or specific to particular kinds of adversity—remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children’s development. PMID:26849071

  13. Parenting begets parenting: A neurobiological perspective on early adversity and the transmission of parenting styles across generations.

    PubMed

    Lomanowska, A M; Boivin, M; Hertzman, C; Fleming, A S

    2017-02-07

    The developing brains of young children are highly sensitive to input from their social environment. Nurturing social experience during this time promotes the acquisition of social and cognitive skills and emotional competencies. However, many young children are confronted with obstacles to healthy development, including poverty, inappropriate care, and violence, and their enhanced sensitivity to the social environment means that they are highly susceptible to these adverse childhood experiences. One source of social adversity in early life can stem from parenting that is harsh, inconsistent, non-sensitive or hostile. Parenting is considered to be the cornerstone of early socio-emotional development and an adverse parenting style is associated with adjustment problems and a higher risk of developing mood and behavioral disorders. Importantly, there is a growing literature showing that an important predictor of parenting behavior is how parents, especially mothers, were parented themselves. In this review, we examine how adversity in early-life affects mothering behavior in later-life and how these effects may be perpetuated inter-generationally. Relying on studies in humans and animal models, we consider evidence for the intergenerational transmission of mothering styles. We then describe the psychological underpinnings of mothering, including responsiveness to young, executive function and affect, as well as the physiological mediators of mothering behavior, including hormones, brain regions and neurotransmitters, and we consider how development in these relevant domains may be affected by adversity experienced in early life. Finally, we explore how genes and early experience interact to predict mothering behavior, including the involvement of epigenetic mechanisms. Understanding how adverse parenting begets adverse parenting in the next generation is critical for designing interventions aimed at preventing this intergenerational cycle of early adversity.

  14. Scrapie Affects the Maturation Cycle and Immune Complex Trapping by Follicular Dendritic Cells in Mice

    PubMed Central

    McGovern, Gillian; Mabbott, Neil; Jeffrey, Martin

    2009-01-01

    Transmissible spongiform encephalopathies (TSEs) or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrPd) accumulations in the brain and lymphoreticular system (LRS). Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrPd accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs) and tingible body macrophages (TBMs). Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs) of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrPd plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrPd accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrPd. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrPd accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function. PMID:19997557

  15. Mechanisms of adverse drug reactions to biologics.

    PubMed

    Clarke, Janet B

    2010-01-01

    Biologics encompass a broad range of therapeutics that include proteins and other products derived from living systems. Although the multiplicity of target organs often seen with new chemical entities is generally not seen with biologics, they can produce significant adverse reactions. Examples include IL-12 and an anti-CD28 antibody that resulted in patient deaths and/or long stays in intensive care units. Mechanisms of toxicities can be categorized as pharmacological or nonpharmacological, with most, excepting hypersensitivity reactions, associated with the interaction of the agent with its planned target. Unexpected toxicities generally arise as a result of previously unknown biology. Manufacturing quality is a significant issue relative to the toxicity of biologics. The development of recombinant technology represented the single biggest advance leading to humanized products with minimal or no contaminants in comparison to products purified from animal tissues. Nevertheless, the type of manufacturing process including choice of cell type, culture medium, and purification method can result in changes to the protein. For example, a change to the closure system for erythropoietin led to an increase in aplastic anemia as a result of changing the immunogenicity characteristics of the protein. Monoclonal antibodies represent a major class of successful biologics. Toxicities associated with these agents include those associated with the binding of the complementary determining region (CDR) with the target. First dose reactions or infusion reactions are generally thought to be mediated via the Fc region of the antibody activating cytokine release, and have been observed with several antibodies. Usually, these effects (flu-like symptoms, etc.) are transient with subsequent dosing. Although biologics can have nonpharmacologic toxicities, these are less common than with small molecule drugs.

  16. Reporting hospital adverse events using the Alfred Hospital's morbidity data.

    PubMed

    Carroll, Rhonda; McLean, Jenny; Walsh, Michael

    2003-01-01

    Hospital morbidity data were analysed to determine their usefulness for reporting adverse events. The entire ICD-10-AM classification system was reviewed in conjunction with the Australian Coding Standards to identify external cause codes and code prefixes associated with adverse events. For the 50,712 separations registered at The Alfred from July 2000-June 2001, 4,740 external cause codes were associated with adverse events. Place of occurrence code CY92.22 was considered the best indicator of the number of separations associated with adverse events. Approximately 4% of all separations were associated with adverse events occurring during an episode of care. Results suggest that hospital morbidity data are useful for monitoring adverse events at hospital level. Reliable reporting across the health care industry requires consistent reporting requirements at state and national levels and the adoption of standard code prefixes nationally.

  17. Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis.

    PubMed

    Becker, Katrin Anne; Riethmüller, Joachim; Lüth, Anja; Döring, Gerd; Kleuser, Burkhard; Gulbins, Erich

    2010-06-01

    Employing genetic mouse models we have recently shown that ceramide accumulation is critically involved in the pathogenesis of cystic fibrosis (CF) lung disease. Genetic or systemic inhibition of the acid sphingomyelinase (Asm) is not feasible for treatment of patients or might cause adverse effects. Thus, a manipulation of ceramide specifically in lungs of CF mice must be developed. We tested whether inhalation of different acid sphingomyelinase inhibitors does reduce Asm activity and ceramide accumulation in lungs of CF mice. The efficacy and specificity of the drugs was determined. Ceramide was determined by mass spectrometry, DAG-kinase assays, and fluorescence microscopy. We determined pulmonary and systemic Asm activity, neutral sphingomyelinase (Nsm), ceramide, cytokines, and infection susceptibility. Mass spectroscopy, DAG-kinase assays, and semiquantitative immune fluorescence microscopy revealed that a standard diet did not influence ceramide in bronchial respiratory epithelial cells, while a diet with Peptamen severely affected the concentration of sphingolipids in CF lungs. Inhalation of the Asm inhibitors amitriptyline, trimipramine, desipramine, chlorprothixene, fluoxetine, amlodipine, or sertraline restored normal ceramide concentrations in murine bronchial epithelial cells, reduced inflammation in the lung of CF mice and prevented infection with Pseudomonas aeruginosa. All drugs showed very similar efficacy. Inhalation of the drugs was without systemic effects and did not inhibit Nsm. These findings employing several structurally different Asm inhibitors identify Asm as primary target in the lung to reduce ceramide concentrations. Inhaling an Asm inhibitor may be a beneficial treatment for CF, with minimal adverse systemic effects.

  18. Clinicians' recognition of the metabolic adverse effects of antipsychotic medications.

    PubMed

    Buckley, Peter F; Miller, Del D; Singer, Beth; Arena, John; Stirewalt, Edna M

    2005-11-15

    There is a growing concern regarding the propensity of second generation antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent consensus guidelines have recommended assessment and monitoring procedures to appropriately detect and manage these adverse effects. This study addresses the appreciation and readiness of clinicians to implement management guidelines for these adverse effects. Respondents indicated awareness of the risks of treatment with SGAs. The extent of monitoring for metabolic adverse effects was low and inconsistent across measures and in frequency of evaluation. Ongoing efforts are needed to support and encourage change in clinician practice.

  19. Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

    PubMed

    Wang, Yan; Fu, Wei; Liu, Jing

    2016-01-01

    Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

  20. Channel shutdown: a response of hippocampal neurons to adverse environments.

    PubMed

    Somjen, G G; Faas, G C; Vreugdenhil, M; Wadman, W J

    1993-12-31

    Stretch-activated ion channels have been discovered in the membrane of many types of cells, but their presence in neurons is uncertain. We used freshly dissociated rat hippocampal neurons to study the effect of hypotonic swelling but, surprisingly, the isolated neurons did not swell. Voltage-dependent whole-cell membrane currents mediated by K+, Na+ and Ca2+ were rapidly and reversibly suppressed during sudden exposure to strongly hypo-osmotic, hyper-osmotic or glucose deficient solutions. The amplitudes of the sustained components of K+ and Ca2+ currents were more depressed than transient currents, but the rate of decay of transient K+ current greatly accelerated. The voltage dependence of activation and of steady state inactivation of residual K+ and Ca2+ currents were not shifted. The current holding membrane potential at -70 mV and therefore the conductance at that voltage were unchanged or somewhat decreased. Capacitive (charging) membrane current was not affected. Changes in tail current suggested moderate loss of cytosolic K+ in some but not in all cells. We conclude that channel shutdown is a uniform response of neuron somata and proximal dendrites to various adverse environments. Hypothetically we propose that swelling was prevented in anisosmotic conditions because membrane water permeability decreased.

  1. [Histamine intolerance - are the criteria of an adverse reaction met?].

    PubMed

    Reese, Imke

    2016-06-01

    Searching the internet for an explaination of recurring symptoms, many people come across the so-called histamine intolerance disorder. Also many practitioners like to diagnose this disorder without making sure that reproducibility, a prerequisite for an adverse reaction, is present. Consequently, presumably affected persons are often advised to follow a low-histamine diet. Depending on the source of information, these diets often avoid a huge variety of foods containing more or less histamine, which has a considerable impact on patient quality of life. While most persons benefit from such a diet in the beginning - this might be due to the change in dietary habits or the expectation of symptom improvement by dieting - in the long run the expected loss of symptoms will not happen. Underlying a diminished capacity for histamine degradation, the lack of partial or complete symptom improvement might be due to the fact that endogenous histamine release is responsible for reactions. The role of ingested histamine is discussed controversially. However, it is more than obvious that the histamine content of a certain food alone is not enough to predict its tolerance.If histamine intolerance is suspected, an individual diagnostic and therapeutic procedure is mandatory in order to minimize avoidance and to preserve a high quality of life. Ideally this is done in a close cooperation between allergologists and nutritionists/dieticians.

  2. New Unintended Adverse Consequences of Electronic Health Records.

    PubMed

    Sittig, D F; Wright, A; Ash, J; Singh, H

    2016-11-10

    Although the health information technology industry has made considerable progress in the design, development, implementation, and use of electronic health records (EHRs), the lofty expectations of the early pioneers have not been met. In 2006, the Provider Order Entry Team at Oregon Health & Science University described a set of unintended adverse consequences (UACs), or unpredictable, emergent problems associated with computer-based provider order entry implementation, use, and maintenance. Many of these originally identified UACs have not been completely addressed or alleviated, some have evolved over time, and some new ones have emerged as EHRs became more widely available. The rapid increase in the adoption of EHRs, coupled with the changes in the types and attitudes of clinical users, has led to several new UACs, specifically: complete clinical information unavailable at the point of care; lack of innovations to improve system usability leading to frustrating user experiences; inadvertent disclosure of large amounts of patient-specific information; increased focus on computer-based quality measurement negatively affecting clinical workflows and patient-provider interactions; information overload from marginally useful computer-generated data; and a decline in the development and use of internally-developed EHRs. While each of these new UACs poses significant challenges to EHR developers and users alike, they also offer many opportunities. The challenge for clinical informatics researchers is to continue to refine our current systems while exploring new methods of overcoming these challenges and developing innovations to improve EHR interoperability, usability, security, functionality, clinical quality measurement, and information summarization and display.

  3. An overview on adverse drug reactions to traditional Chinese medicines

    PubMed Central

    Chan, Kelvin; Zhang, Hongwei; Lin, Zhi-Xiu

    2015-01-01

    The safe use of Chinese materia medica (CMM) and products in traditional Chinese medicine (TCM) practice conventionally relies on correct pharmacognostic identification, good agricultural and manufacturing practices based on pharmacopoeia standards and rational/correct CMM combinations with TCM-guided clinical prescribing. These experience-based principles may not absolutely ensure safety without careful toxicological investigations when compared with development of new pharmaceutical drugs. Clinically observed toxicity reports remain as guidance for gathering toxicological evidence, though essential as pharmacovigilance, but are considered as late events for ensuring safety. The overview focuses on the following factors: global development of TCM that has affected conventional healthcare; examples of key toxic substances in CMM; reported adverse drug reactions (ADRs) consequential to taking CMM and TCM products; and proposals on rational approaches to integrate the knowledge of biomedical science and the principles of TCM practice for detecting early ADRs if both TCM products and orthodox drugs are involved. It is envisaged that good control of the quality and standards of CMM and proprietary Chinese medicines can certainly reduce the incidence of ADRs in TCM practice when these medications are used. PMID:25619530

  4. Neighborhood adversity, child health, and the role for community development.

    PubMed

    Jutte, Douglas P; Miller, Jennifer L; Erickson, David J

    2015-03-01

    Despite medical advances, childhood health and well-being have not been broadly achieved due to rising chronic diseases and conditions related to child poverty. Family and neighborhood living conditions can have lasting consequences for health, with community adversity affecting health outcomes in significant part through stress response and increased allostatic load. Exposure to this "toxic stress" influences gene expression and brain development with direct and indirect negative consequences for health. Ensuring healthy child development requires improving conditions in distressed, high-poverty neighborhoods by reducing children's exposure to neighborhood stressors and supporting good family and caregiver functioning. The community development industry invests more than $200 billion annually in low-income neighborhoods, with the goal of improving living conditions for residents. The most impactful investments have transformed neighborhoods by integrating across sectors to address both the built environment and the social and service environment. By addressing many facets of the social determinants of health at once, these efforts suggest substantial results for children, but health outcomes generally have not been considered or evaluated. Increased partnership between the health sector and community development can bring health outcomes explicitly into focus for community development investments, help optimize intervention strategies for health, and provide natural experiments to build the evidence base for holistic interventions for disadvantaged children. The problems and potential solutions are beyond the scope of practicing pediatricians, but the community development sector stands ready to engage in shared efforts to improve the health and development of our most at-risk children.

  5. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  6. Incontinence-associated dermatitis: reducing adverse events.

    PubMed

    Rippon, Mark; Colegrave, Melanie; Ousey, Karen

    2016-10-13

    Incontinence-associated dermatitis (IAD) is a common problem in patients with faecal and/or urinary incontinence. Urine alters the normal skin flora and increases permeability of the stratum corneum and faecal enzymes on the skin contribute to skin damage. Faecal bacteria can then penetrate the skin, increasing the risk of secondary infection. However, IAD can be prevented and healed with timely and appropriate skin cleansing and skin protection. This includes appropriate use of containment devices. This article also looks at HARTMANN incontinence pads that have been developed to absorb the fluids that cause IAD and maintain the skin's acidic pH. The acidic pH of the skin contributes to its barrier function and defence against infection. Therefore, maintaining an acidic pH will help protect the skin from damage.

  7. Safety Profile of Finasteride: Distribution of Adverse Effects According to Structural and Informational Dichotomies of the Mind/Brain.

    PubMed

    Motofei, Ion G; Rowland, David L; Manea, Mirela; Georgescu, Simona R; Păunică, Ioana; Sinescu, Ioanel

    2017-02-04

    Finasteride is currently used extensively for male androgenic alopecia and benign prostatic hyperplasia; however, some adverse effects are severe and even persistent after treatment cessation, the so-called 'post-finasteride syndrome'. The following most severe adverse effects-sexual dysfunction and depression-often occur together and may potentiate one other, a fact that could explain (at least in part) the magnitude and persistence of finasteride adverse effects. This paper presents the pharmacological action of finasteride and the corresponding adverse effects, the biological base explaining the occurrence, persistence and distribution of these adverse effects, and a possible therapeutic solution for post-finasteride syndrome. The distribution of finasteride adverse effects is presented within a comprehensive and modern neuro-endocrine perspective related to structural and informational dichotomies of the brain. Understanding the variation of finasteride side effects among different populations would be necessary not only to delineate the safety profile of finasteride for different subgroups of men (a subject may or may not be affected by a certain anti-hormonal compound dependent on the individual neuro-endocrine profile), but also as a possible premise for a therapeutic approach of finasteride adverse effects. Such therapeutic approach should include administration of exogenous hormones, which are deficient in men with post-finasteride syndrome, namely dihydrotestosterone (in right-handed men) or progesterone/dihydroprogesterone (in left-handed subjects).

  8. Transfusion related adverse events in the Platelet Dose study

    PubMed Central

    Kaufman, Richard M.; Assmann, Susan F.; Triulzi, Darrell J.; Strauss, Ronald G.; Ness, Paul; Granger, Suzanne; Slichter, Sherrill J.

    2014-01-01

    BACKGROUND How platelet (PLT) product characteristics such as dose, source (whole blood-derived (WBD) vs. apheresis), storage duration, and ABO matching status affect the risks of transfusion-related adverse events (TRAEs) is unclear. Similarly, more information is needed to define how recipient characteristics affect the frequency of TRAEs following PLT transfusion. STUDY DESIGN AND METHODS In the multicenter Platelet Dose (“PLADO”) study, pediatric and adult hematology-oncology patients with hypoproliferative thrombocytopenia were randomized to receive low-dose (LD), medium-dose (MD), or high-dose (HD) PLT prophylaxis for a pre-transfusion PLT count ≤10,000/μL. All PLT units (apheresis or WBD) were leukoreduced. Post hoc analyses of PLADO data were performed using multi-predictor models. RESULTS 5034 PLT transfusions to 1102 patients were analyzed. A TRAE occurred with 501 PLT transfusions (10.0%). The most common TRAEs were fever (6.6% of transfusions), allergic/hypersensitivity reactions (1.9%), and sinus tachycardia (1.8%). Patients assigned HD PLTs were more likely than LD or MD patients to experience any TRAE (OR for HD vs. MD 1.50, 95% CI (1.10, 2.05), three-group comparison p=0.02). PLT source and ABO matching status were not significantly related to overall TRAE risk. Compared to a patient’s first PLT transfusion, subsequent PLT transfusions were less likely to have a TRAE reported, primarily due to a lower risk of allergic/hypersensitivity reactions. CONCLUSION The most important PLT unit characteristic associated with TRAEs was PLT dose per transfusion. HD PLTs may increase the risk of TRAEs, and LD PLTs may reduce the risk. PMID:25065959

  9. Vertigo/dizziness as a Drugs’ adverse reaction

    PubMed Central

    Chimirri, Serafina; Aiello, Rossana; Mazzitello, Carmela; Mumoli, Laura; Palleria, Caterina; Altomonte, Mariolina; Citraro, Rita; De Sarro, Giovambattista

    2013-01-01

    Introduction: Vertigo, dizziness, and nausea encompass a spectrum of balance-related symptoms caused by a variety of etiologies. Balance is affected by many systems: Proprioceptive pathways and visual, cerebellar, vestibulocochlear, and vascular / vasovagal systems. Vertigo is a subtype of dizziness, in which a subject, as a result to a dysfunction of the vestibular system, improperly experiments the perception of motion. The most useful clinical subdivision is to categorize vertigo into true vertigo and pseudovertigo, whereas from a pathophysiological point of view, vertigo can be classified into central, peripheral, and psychogenic. It is not easy to identify the cause of vertigo since the patients often are not able to precisely describe their symptoms. An impressive list of drugs may cause vertigo or dizziness. Materials and Methods: The aim of the present study was to analyze the data extracted from the reporting cards of the ADRs (adverse drug reactions), received at our Pharmacovigilance Regional Center (Calabria, Italy) in 2012. In particular, the data concerning the occurrence of vertigo and dizziness, after taking certain classes of drugs, have been considered. Results: Our results show that, among the side-effects of different classes of drugs such as anti-convulsants, anti-hypertensives, antibiotics, anti-depressants, anti-psychotics, and anti-inflammatory, also vertigo or dizziness are included. Conclusions: Spontaneous reports of vertigo or dizziness, as side-effect of certain drugs, received at our Pharmacovigilance Center, represented the 5% of all reports in 2012. Considering the high incidence of such an ADR for several drugs’ classes, it can be speculated that under-reporting also affect vertigo and dizziness. Despite the fact that these ADRs might not represent a direct threaten for life, indirectly they can cause secondary damage to patients such as falls, fractures etc. Balance should be accurately monitored during drug use and particularly

  10. An upside to adversity?: moderate cumulative lifetime adversity is associated with resilient responses in the face of controlled stressors.

    PubMed

    Seery, Mark D; Leo, Raphael J; Lupien, Shannon P; Kondrak, Cheryl L; Almonte, Jessica L

    2013-07-01

    Despite common findings suggesting that lack of negative life events should be optimal, recent work has revealed a curvilinear pattern, such that some cumulative lifetime adversity is instead associated with optimal well-being. This work, however, is limited in that responses to specific stressors as they occurred were not assessed, thereby precluding investigation of resilience. The current research addressed this critical gap by directly testing the relationship between adversity history and resilience to stressors. Specifically, we used a multimethod approach across two studies to assess responses to controlled laboratory stressors (respectively requiring passive endurance and active instrumental performance). Results revealed hypothesized U-shaped relationships: Relative to a history of either no adversity or nonextreme high adversity, a moderate number of adverse life events was associated with less negative responses to pain and more positive psychophysiological responses while taking a test. These results provide novel evidence in support of adversity-derived propensity for resilience that generalizes across stressors.

  11. On the impact of adverse pressure gradient on the supersonic turbulent boundary layer

    NASA Astrophysics Data System (ADS)

    Wang, Qian-Cheng; Wang, Zhen-Guo; Zhao, Yu-Xin

    2016-11-01

    By employing the particle image velocimetry, the mean and turbulent characteristics of a Mach 2.95 turbulent boundary layer are experimentally investigated without the impact of curvature. The physical mechanism with which the streamwise adverse pressure gradient affects the supersonic boundary layer is revealed. The data are compared to that of the concave boundary layer with similar streamwise distributions of wall static pressure to clarify the separate impacts of the adverse pressure gradient and the concave curvature. The logarithmic law is observed to be well preserved for both of the cases. The dip below the logarithmic law is not observed in present investigation. Theoretical analysis indicates that it could be the result of compromise between the opposite impacts of the compression wave and the increased turbulent intensity. Compared to the zero pressure gradient boundary layer, the principal strain rate and the turbulent intensities are increased by the adverse pressure gradient. The shear layer formed due the hairpin packets could be sharpened by the compression wave, which leads to higher principal strain rate and the associated turbulent level. Due to the additional impact of the centrifugal instability brought by the concave wall, even higher turbulent intensities than that of the adverse pressure gradient case are introduced. The existence of velocity modes within the zero pressure gradient boundary layer suggests that the large scale motions are statistically well organized. The generation of new velocity modes due to the adverse pressure gradient indicates that the turbulent structure is changed by the adverse pressure gradient, through which more turbulence production that cannot be effectively predicted by the Reynolds-stress transport equations could be brought.

  12. Alterations in cognitive performance and affect-arousal state during fluctuations in motor function in Parkinson's disease.

    PubMed Central

    Brown, R G; Marsden, C D; Quinn, N; Wyke, M A

    1984-01-01

    Sixteen patients with idiopathic Parkinson's disease were selected who were all showing severe fluctuations in motor function ("on-off" phenomenon). Measures of cognitive function and of subjective affect/arousal state were taken on two occasions, once when "on" and once when "off". Twenty-five matched normal controls were also assessed on the same measures. Results revealed, on the average, a drop in cognitive function plus an adverse swing in affect/arousal state, in the patient group in the "off" condition, compared to the levels when "on". Analysis of the data suggested that the main factor associated with cognitive function when "off" was not the severity of disability but the level of affect/arousal. The fluctuations in cognitive function found tended to be mild relative to the severe changes in motor ability, and were present in only a proportion of patients. PMID:6736975

  13. 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

  14. Workplace Bullying: A Tale of Adverse Consequences

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    Workplace bullying is defined as the repetitive and systematic engagement of interpersonally abusive behaviors that negatively affect both the targeted individual and the work organization. According to the findings of 12 studies, being bullied in the workplace affects approximately 11 percent of workers. Victims are frequently blue-collar and unskilled workers. However, there also appear to be gender and milieu/management factors. Emotional/psychological consequences of workplace bullying may include increased mental distress, sleep disturbances, fatigue in women and lack of vigor in men, depression and anxiety, adjustment disorders, and even work-related suicide. Medical consequences of workplace bullying may include an increase in health complaints such as neck pain, musculoskeletal complaints, acute pain, fibromyalgia, and cardiovascular symptoms. Finally, socioeconomic consequences of workplace bullying may include absenteeism due to sick days and unemployment. Clinicians in both mental health and primary care settings need to be alert to the associations between bullying in the workplace and these potential negative consequences, as patients may not disclose workplace maltreatment due to embarrassment or fears of retribution. PMID:25852978

  15. Analysis of Neuropsychiatric Adverse Events in Patients Treated with Oseltamivir in Spontaneous Adverse Event Reports.

    PubMed

    Ueda, Natsumi; Umetsu, Ryogo; Abe, Junko; Kato, Yamato; Nakayama, Yoko; Kato, Zenichiro; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2015-01-01

    There have been concerns that oseltamivir causes neuropsychiatric adverse events (NPAEs). We analyzed the association of age and gender with NPAEs in patients treated with oseltamivir using a logistic regression model. NPAE data were obtained from the U.S. Food and Drug Administration Adverse Event Reporting System (2004 to 2013). The lower limit of the reporting odds ratio (ROR) 95% confidence interval (CI) of "abnormal behavior" in Japan, Singapore, and Taiwan was ≥1. The effects of the interaction terms for oseltamivir in male patients aged 10-19 years were statistically significant. The adjusted ROR of "abnormal behavior" was 96.4 (95% CI, 77.5-119.9) in male patients aged 10-19 years treated with osletamivir. In female patients, the results of the likelihood ratio test for "abnormal behavior" were not statistically significant. The adjusted NPAE RORs were increased in male and female patients under the age of 20 years. Oseltamivir use could be associated with "abnormal behavior" in males aged 10-19 years. After considering the causality restraints of the current analysis, further epidemiological studies are recommended.

  16. Normal osteoid tissue

    PubMed Central

    Raina, Vinita

    1972-01-01

    The results of a histological study of normal osteoid tissue in man, the monkey, the dog, and the rat, using thin microtome sections of plastic-embedded undecalcified bone, are described. Osteoid tissue covers the entire bone surface, except for areas of active resorption, although the thickness of the layer of osteoid tissue varies at different sites and in different species of animals. The histological features of osteoid tissue, apart from its amount, are the same in the different species studied. Distinct bands or zones are recognizable in some layers of osteoid tissue, particularly those of greatest thickness, and their significance is discussed. Some of the histological features of the calcification front are described. Images PMID:4111820

  17. Normal Untreated Jurkat Cells

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. The objective of the research was to define a way to differentiate between effects due to microgravity and those due to possible stress from non-optimal spaceflight conditions. These Jurkat cells, a human acute T-cell leukemia was obtained to evaluate three types of potential experimental stressors: a) Temperature elevation; b) Serum starvation; and c) Centrifugal force. The data from previous spaceflight experiments showed that actin filaments and cell shape are significantly different for the control. These normal cells serve as the baseline for future spaceflight experiments.

  18. Pornography, normalization, and empowerment.

    PubMed

    Weinberg, Martin S; Williams, Colin J; Kleiner, Sibyl; Irizarry, Yasmiyn

    2010-12-01

    Opponents and proponents of erotic representations (referred to hereafter as "pornography") have described the effects of pornography from their perspective. Little, however, has been done in the way of research to investigate these claims from the consumer's point of view. This especially has been so regarding the positive impact of such consumption on a person's sex life. Using a study group of 245 college students, we examined this question in a framework of scripting theory. We wanted to see whether viewing pornography appeared to expand sexual horizons through normalization and facilitate a willingness to explore new sexual behaviors and sexual relationships through empowerment. The data supported this viewpoint and further showed the effects to be mediated by gender and sexual preference identity. They suggested, however, that established scripts were extended rather than abandoned. We conclude with connections between our findings and the widespread viewing of pornography in contemporary society.

  19. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

    PubMed Central

    Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

    2015-01-01

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  20. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

  1. Population versus Customized Fetal Growth Norms and Adverse Outcomes in an Intrapartum Cohort

    PubMed Central

    Costantine, Maged M.; Lai, Yinglei; Bloom, Steven L.; Spong, Catherine Y.; Varner, Michael W.; Rouse, Dwight J.; Ramin, Susan M.; Caritis, Steve N.; Peaceman, Alan M.; Sorokin, Yoram; Sciscione, Anthony; Mercer, Brian M.; Thorp, John M.; Malone, Fergal D.; Harper, Margaret; Iams, Jay D.

    2013-01-01

    Objective To compare population versus customized fetal growth norms in identifying neonates at risk for adverse outcomes (APO) associated with small for gestational age (SGA). Study Design Secondary analysis of an intrapartum fetal pulse oximetry trial in nulliparous women at term. Birthweight percentiles were calculated using ethnicity- & gender-specific population norms and customized norms (Gardosi). Results 508 (9.9%) and 584 (11.3%) neonates were SGA by population (SGApop) and customized (SGAcust) norms. SGApop infants were significantly associated with a composite adverse neonatal outcome, neonatal intensive care admission, low fetal oxygen saturation and reduced risk of cesarean delivery; while both SGApop and SGAcust were associated with a 5-minute Apgar score < 4. The ability of customized and population birthweight percentiles in predicting APO was poor (12 out of 14 APOs had AUC <0.6). Conclusion In this intrapartum cohort, neither customized nor normalized-population norms adequately identify neonates at risk of APO related to SGA. PMID:22893556

  2. 42 CFR 456.124 - Notification of adverse decision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Notification of adverse decision. 456.124 Section 456.124 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN...: Review of Need for Admission 1 § 456.124 Notification of adverse decision. The UR plan must provide...

  3. Adverse Outcome Pathways: From Research to Regulation - Scientific Workshop Report

    EPA Science Inventory

    An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify...

  4. 43 CFR 3871.5 - Termination of adverse suit.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Termination of adverse suit. 3871.5 Section 3871.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) ADVERSE CLAIMS, PROTESTS AND...

  5. 43 CFR 3871.5 - Termination of adverse suit.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Termination of adverse suit. 3871.5 Section 3871.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) ADVERSE CLAIMS, PROTESTS AND...

  6. 43 CFR 3871.5 - Termination of adverse suit.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Termination of adverse suit. 3871.5 Section 3871.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) ADVERSE CLAIMS, PROTESTS AND...

  7. 43 CFR 3871.5 - Termination of adverse suit.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Termination of adverse suit. 3871.5 Section 3871.5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) ADVERSE CLAIMS, PROTESTS AND...

  8. Intimate Partner Violence, PTSD, and Adverse Health Outcomes

    ERIC Educational Resources Information Center

    Dutton, Mary Ann; Green, Bonnie L.; Kaltman, Stacey I.; Roesch, Darren M.; Zeffiro, Thomas A.; Krause, Elizabeth D.

    2006-01-01

    The high prevalence of adverse health outcomes related to intimate partner violence (IPV) is well documented. Yet we know little about the pathways that lead to adverse health outcomes. Research concerning the psychological, biological, neurological, behavioral, and physiological alterations following exposure to IPV--many of which are associated…

  9. Adversity Quotient and Defense Mechanism of Secondary School Students

    ERIC Educational Resources Information Center

    Nikam, Vibhawari B.; Uplane, Megha M.

    2013-01-01

    The present study was conducted to explore the relationship between Adversity Quotient (AQ) and Defense Mechanism (DM) of secondary school students. The aim of the study was to ascertain relationship between Adversity Quotient and Defense mechanism i. e. Turning against object (TAO), Projection (PRO), Turning against self (TAS), Principalisation…

  10. Adverse Selection in Health Insurance Markets: A Classroom Experiment

    ERIC Educational Resources Information Center

    Hodgson, Ashley

    2014-01-01

    Adverse selection as it relates to health care policy will be a key economic issue in many upcoming elections. In this article, the author lays out a 30-minute classroom experiment designed for students to experience the kind of elevated prices and market collapse that can result from adverse selection in health insurance markets. The students…

  11. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  12. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  13. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  14. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  15. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  16. 34 CFR 5.40 - Appeals of adverse determinations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Appeals of adverse determinations. 5.40 Section 5.40 Education Office of the Secretary, Department of Education AVAILABILITY OF INFORMATION TO THE PUBLIC Administrative Review § 5.40 Appeals of adverse determinations. (a) In general. A requester may seek...

  17. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... only referred to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and.... (b) Review of adverse experiences. Any person having a biologics license under § 601.20 of this... Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports...

  18. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... only referred to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and.... (b) Review of adverse experiences. Any person having a biologics license under § 601.20 of this... Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports...

  19. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... only referred to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and.... (b) Review of adverse experiences. Any person having a biologics license under § 601.20 of this... Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports...

  20. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... only referred to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and.... (b) Review of adverse experiences. Any person having a biologics license under § 601.20 of this... Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports...