The relation between family adversity and social anxiety among adolescents in Taiwan: effects of family function and self-esteem.

PubMed

Yen, Cheng-Fang; Yang, Pinchen; Wu, Yu-Yu; Cheng, Chung-Ping

2013-11-01

This study aimed to examine the relationship between three indicators of family adversity (domestic violence, family substance use, and broken parental marriage) and the severity of social anxiety among adolescents in Taiwan, as well as the mediating effects of perceived family function and self-esteem on that relationship, using structural equation modeling (SEM). A total of 5607 adolescents completed the social anxiety subscale of the Multidimensional Anxiety Scale for Children; the Family APGAR Index; the Rosenberg Self-Esteem Scale; and a questionnaire for domestic violence, family substance use, and broken parental marriage. The relation between family adversity and social anxiety, as well as the mediating effects of family function and self-esteem, was examined using SEM. SEM analysis revealed that all three indicators of family adversity reduced the level of family function, that decreased family function compromised the level of self-esteem, and that a low level of self-esteem further increased the severity of social anxiety. The results indicated that, along with intervening to change family adversity, evaluating and improving adolescents' self-esteem and family function are also important clinical issues when helping adolescents reduce their social anxiety.

Area-Level Deprivation and Adverse Consequences in People With Substance Use Disorders: Findings From the Psychiatric and Addictive Dual Disorder in Italy (PADDI) Study.

PubMed

Carrà, Giuseppe; Crocamo, Cristina; Borrelli, Paola; Tabacchi, Tommaso; Bartoli, Francesco; Popa, Ioana; Montomoli, Cristina; Clerici, Massimo

2017-03-21

Environmental factors may operate with individual ones to influence the risk of substance use. Research has focused on severe adverse consequences influenced by contextual variables. However, the literature on community level factors influencing substance use behaviors is relatively limited across Europe so far. We capitalized on data from a National survey, exploring individual and contextual characteristics, to study adverse consequences among people with substance use disorders. The impact of area-level deprivation on nonfatal overdose, hepatitis C or B infections, and major involvement with the criminal justice system, was explored. Logistic regression models with cluster-robust errors, modeling subject-level and area-level effects, were used. Living in deprived and intermediate areas, as compared with affluent ones, was associated with greater likelihood of both nonfatal overdose and jail sentences longer than 6 months, though not of active viral hepatitis. Area-level deprivation may play an important role in determining adverse consequences in people with substance use disorders, also after controlling for individual-level characteristics. More research is needed to understand the aspects of social and physical environments that matter for drug outcomes before effective policy and research interventions can be developed.

Quantitative Adverse Outcome Pathway for Neurodevelopmental Effects of Thyroid Peroxidase-Induced Thyroid Hormone Synthesis Inhibition

EPA Science Inventory

Adequate levels of thyroid hormones (TH) are needed for proper brain development and deficiencies lead to adverse neurological outcomes in humans and in animal models. Environmental chemicals have been shown to disrupt TH levels, yet the relationship between developmental exposur...

Cognitive Performance Under Electroconvulsive Therapy (ECT) in ECT-Naive Treatment-Resistant Patients With Major Depressive Disorder.

PubMed

Ziegelmayer, Christoph; Hajak, Göran; Bauer, Anne; Held, Marion; Rupprecht, Rainer; Trapp, Wolfgang

2017-06-01

Although electroconvulsive therapy (ECT) is considered a safe and highly effective treatment option for major depressive disorder, there are still some reservations with regard to possible adverse cognitive adverse effects. This is the case despite a large body of evidence showing that these deficits are transient and that there even seems to be a long-term improvement of cognitive functioning level. However, most data concerning cognitive adverse effects stem from studies using mixed samples of treatment-resistant and non-treatment-resistant as well as ECT-naive and non-ECT-naive subjects. Furthermore, neurocognitive measures might partly be sensitive to practice effects and improvements in depressive symptom level. We examined neurocognitive performance in a sample of 20 treatment-resistant and ECT-naive subjects using repeatable neurocognitive tests, whereas changes in depressive symptom level were controlled. Cognitive functioning level was assessed before (baseline), 1 week, and 6 months (follow-up 1 and 2) after (12 to) 15 sessions of unilateral ECT treatment. No adverse cognitive effects were observed in any of the cognitive domains examined. Instead, a significant improvement in verbal working memory performance was found from baseline to follow-up 2. When changes in depressive symptom levels were controlled statistically, this improvement was no longer seen. Although findings that ECT does not lead to longer lasting cognitive deficits caused by ECT were confirmed, our study adds evidence that previous results of a beneficial effect of ECT on cognition might be questioned.

The joint contribution of maternal history of early adversity and adulthood depression to socioeconomic status and potential relevance for offspring development.

PubMed

Bouvette-Turcot, Andrée-Anne; Unternaehrer, Eva; Gaudreau, Hélène; Lydon, John E; Steiner, Meir; Meaney, Michael J

2017-01-01

We examined the interactive effects of maternal childhood adversity and later adulthood depression on subsequent socioeconomic status (SES). Our community sample ranged from 230 to 243 mothers (across measures) drawn from a prospective, longitudinal cohort study. Maternal childhood adversity scores were derived using an integrated measure derived from the Childhood Trauma Questionnaire (CTQ) and the Parental Bonding Index (PBI). Maternal depression was measured in the prenatal period with the Center for Epidemiologic Studies Depression Scale (CES-D). SES measures included maternal highest level of education and family income as obtained prenatally. The analyses yielded significant interaction effects between maternal childhood adversity and prenatal depression that predicted income, prenatally. Women who reported higher levels of childhood adversity combined with higher levels of self-reported depressive symptoms were significantly more likely to live in low SES environments. Results also showed that level of education was predicted by childhood adversity independent of maternal symptoms of depression. The results suggest that SES is influenced by a life course pathway that begins in childhood and includes adversity-related mental health outcomes. Since child health and development is influenced by both maternal mental health and SES, this pathway may also contribute to the intergenerational transmission of the risk for psychopathology in the offspring. The results also emphasize the importance of studying potential precursors of low SES, a well-documented environmental risk factor for poor developmental outcomes in the offspring. Copyright © 2016. Published by Elsevier B.V.

Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men.

PubMed

Jensen, Sarah K G; Dickie, Erin W; Schwartz, Deborah H; Evans, C John; Dumontheil, Iroise; Paus, Tomáš; Barker, Edward D

2015-10-01

Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child's life (including prenatal exposure) and the child's internalizing symptoms between age 7 and 13 years. Early childhood adversity. The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = -.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = -.20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (β = .37; P < .001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (β = -.08; 95% CI, -0.14 to -0.01; P = .02). Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression.

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.

Can Erythrocytes Transmit Oxidative Stress Beyond the Lungs? An Adverse Outcome Pathway for the Cardiovascular Effects of Air Pollution.

EPA Science Inventory

Adverse outcome pathways (AOPs) are systems biology roadmaps with potential utility in xenobiotic exposure risk assessment. AOPs connect molecular initiating events (MIEs) to population-level adverse outcomes (AOs) via cellular, organ, and organism key events (KE) and KE relatio...

Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies

EPA Science Inventory

Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and dep...

Constructing Adverse Outcome Pathways: a Demonstration of an Ontology-based Semantics Mapping Approach

EPA Science Inventory

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 ...

Chemical Risk Assessment: Selected Federal Agencies’ Procedures, Assumptions, and Policies

DTIC Science & Technology

2001-08-01

adverse effects of exposures to hazardous substances or situations. It is a complex but valuable set of tools for federal regulatory agencies, helping...Act DES diethylstilbestrol DOT Department of Transportation ED effective dose EPA Environmental Protection Agency EPCRA Emergency Planning and...ISO International Organization for Standardization LED lowest effective dose LOAEL lowest observed adverse effect level LOEL lowest observed effect

The Lifetime Effect of Residential School Attendance on Indigenous Health Status

PubMed Central

2014-01-01

Objectives. I examined the health impact of lifetime Indian Residential school (IRS) attendance and the mediating influences of socioeconomic status and community adversity on health outcomes in a national sample of Aboriginal peoples in Canada. Methods. In an analysis of data on 13 881 Inuit, Métis, and off-reserve First Nations or North American Indian adults responding to the postcensus 2006 Aboriginal Peoples Survey administered October 2006 to March 2007, I tested the direct effect of IRS attendance on health and indirect effects through socioeconomic and community factors using logistic regression procedures. Results. Negative health status was significantly more likely with IRS attendance than nonattendance. The direct effect of IRS attendance remained significant although it attenuated substantially when adjusting for demographic characteristics, socioeconomic status, and community-level adversities. Community adversity and socioeconomic factors, primarily income, employment status, and educational attainment mediated the effect of IRS on health. Conclusions. Residential school attendance is a significant health determinant in the Indigenous population and is adversely associated with subsequent health status both directly and through the effects of attendance on socioeconomic and community-level risks. PMID:24328622

Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

PubMed Central

Miyaoka, Tsuyoshi; Tsuji, Seiichi; Inami, Yasushi; Nishida, Akira; Horiguchi, Jun

2010-01-01

Objective: Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject. Data Sources: Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. Study Selection and Data Extraction: Publications relevant to the objective of this article were obtained (1992–2010), and some adverse neuropsychiatric reactions were summarized. Data Synthesis: Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem. Conclusions: Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem. PMID:21494350

Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide.

PubMed

Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John

2018-06-01

Brain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder. Brain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity. This study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects

PubMed Central

Cronin, Mark T.D.; Enoch, Steven J.; Mellor, Claire L.; Przybylak, Katarzyna R.; Richarz, Andrea-Nicole; Madden, Judith C.

2017-01-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given. PMID:28744348

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects.

PubMed

Cronin, Mark T D; Enoch, Steven J; Mellor, Claire L; Przybylak, Katarzyna R; Richarz, Andrea-Nicole; Madden, Judith C

2017-07-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given.

Adverse effects of ketoconazole in dogs--a retrospective study.

PubMed

Mayer, Ursula K; Glos, Katharina; Schmid, Matthias; Power, Helen T; Bettenay, Sonya V; Mueller, Ralf S

2008-08-01

Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.

A Review of Nitrates in Drinking Water: Maternal Exposure and Adverse Reproductive and Developmental Outcomes

PubMed Central

Manassaram, Deana M.; Backer, Lorraine C.; Moll, Deborah M.

2006-01-01

In this review we present an update on maternal exposure to nitrates in drinking water in relation to possible adverse reproductive and developmental effects, and also discuss nitrates in drinking water in the United States. The current standard for nitrates in drinking water is based on retrospective studies and approximates a level that protects infants from methemoglobinemia, but no safety factor is built into the standard. The current standard applies only to public water systems. Drinking water source was related to nitrate exposure (i.e., private systems water was more likely than community system water to have nitrate levels above the maximum contaminant limit). Animal studies have found adverse reproductive effects resulting from higher doses of nitrate or nitrite. The epidemiologic evidence of a direct exposure–response relationship between drinking water nitrate level and adverse reproductive effect is still not clear. However, some reports have suggested an association between exposure to nitrates in drinking water and spontaneous abortions, intrauterine growth restriction, and various birth defects. Uncertainties in epidemiologic studies include the lack of individual exposure assessment that would rule out confounding of the exposure with some other cause. Nitrates may be just one of the contaminants in drinking water contributing to adverse outcomes. We conclude that the current literature does not provide sufficient evidence of a causal relationship between exposure to nitrates in drinking water and adverse reproductive effects. Future studies incorporating individual exposure assessment about users of private wells—the population most at risk—should be considered. PMID:16507452

Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome.

PubMed

Yonggang, Huang; Xiaosheng, Lu; Zhaoxia, Huang; Yilu, Chen; Jiqiang, Lv; Huina, Zhang

2017-02-01

Effects of human chorionic gonadotropin combined with clomiphene on serum E 2 , FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed. 90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E 2 , FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated. Serum E 2 , FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant ( P  < 0.05). After the treatment, E 2 , FSH, LH and PRL levels in the observation group were lower than that in the control group and the difference is statistical significant ( P  < 0.05). Total effective rate was 64.44% in the control group and 93.33% in the observation group. There were statistically significant difference in clinical curative effects in the two groups ( P  < 0.05). Different degrees of adverse reactions were found in both groups during treatment, such as nausea, vomiting, anorexia, liver dysfunction. There were 2 cases of nausea, 2 cases of vomiting, 3 cases of anorexia and 1 case of liver dysfunction from the 45 patients in control group. The total incidence of adverse reactions was 17.78% (8/45). There were 1 case of nausea, 1 case of vomiting, 1 case of anorexia and no liver dysfunction from the 45 patients in observation group. The total incidence of adverse reactions was 6.67% (3/45). The total incidence of adverse reactions in the observation group was significantly higher than that in the control group and the difference was not statistically significant ( P  > 0.05). Combined use of human chorionic gonadotropin can significantly reduce serum E 2 , FSH, LH and PRL levels, improve clinical curative effects and reduce the incidence of adverse reactions. Human chorionic gonadotropin has high application value on the treatment of polycystic ovary syndrome.

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

Impact of early life adversity on EMG stress reactivity of the trapezius muscle.

PubMed

Luijcks, Rosan; Vossen, Catherine J; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J; Lousberg, Richel

2016-09-01

Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies.

Improving patient safety by optimizing the use of nursing human resources.

PubMed

Rochefort, Christian M; Buckeridge, David L; Abrahamowicz, Michal

2015-06-14

Recent ecological studies have suggested that inadequate nurse staffing may contribute to the incidence of adverse events in acute care hospitals. However, longitudinal studies are needed to further examine these associations and to identify the staffing patterns that are of greatest risk. The aims of this study are to determine if (a) nurse staffing levels are associated with an increased risk of adverse events, (b) the risk of adverse events in relationship to nurse staffing levels is modified by the complexity of patient requirements, and (c) optimal nurse staffing levels can be established. A dynamic cohort of all adult medical, surgical, and intensive care unit patients admitted between 2010 and 2015 to a Canadian academic health center will be followed during the inpatient and 7-day post-discharge period to assess the occurrence and frequency of adverse events in relationship to antecedent nurse staffing levels. Four potentially preventable adverse events will be measured: (a) hospital-acquired pneumonia, (b) ventilator-associated pneumonia, (c) venous thromboembolism, and (d) in-hospital fall. These events were selected for their high incidence, morbidity and mortality rates, and because they are hypothesized to be related to nurse staffing levels. Adverse events will be ascertained from electronic health record data using validated automated detection algorithms. Patient exposure to nurse staffing will be measured on every shift of the hospitalization using electronic payroll records. To examine the association between nurse staffing levels and the risk of adverse events, four Cox proportional hazards regression models will be used (one for each adverse event), while adjusting for patient characteristics and risk factors of adverse event occurrence. To determine if the association between nurse staffing levels and the occurrence of adverse events is modified by the complexity of patient requirements, interaction terms will be included in the regression models, and their significance assessed. To assess for the presence of optimal nurse staffing levels, flexible nonlinear spline functions will be fitted. This study will likely generate evidence-based information that will assist managers in making the most effective use of scarce nursing resources and in identifying staffing patterns that minimize the risk of adverse events.

No impact of DvSnf7 RNA on honey bee (Apis mellifera L.) adults and larvae in dietary feeding tests.

PubMed

Tan, Jianguo; Levine, Steven L; Bachman, Pamela M; Jensen, Peter D; Mueller, Geoffrey M; Uffman, Joshua P; Meng, Chen; Song, Zihong; Richards, Kathy B; Beevers, Michael H

2016-02-01

The honey bee (Apis mellifera L.) is the most important managed pollinator species worldwide and plays a critical role in the pollination of a diverse range of economically important crops. This species is important to agriculture and historically has been used as a surrogate species for pollinators to evaluate the potential adverse effects for conventional, biological, and microbial pesticides, as well as for genetically engineered plants that produce pesticidal products. As part of the ecological risk assessment of MON 87411 maize, which expresses a double-stranded RNA targeting the Snf7 ortholog (DvSnf7) in western corn rootworm (Diabrotica virgifera virgifera), dietary feeding studies with honey bee larvae and adults were conducted. Based on the mode of action of the DvSnf7 RNA in western corn rootworm, the present studies were designed to be of sufficient duration to evaluate the potential for adverse effects on larval survival and development through emergence and adult survival to a significant portion of the adult stage. Testing was conducted at concentrations of DvSnf7 RNA that greatly exceeded environmentally relevant exposure levels based on expression levels in maize pollen. No adverse effects were observed in either larval or adult honey bees at these high exposure levels, providing a large margin of safety between environmental exposure levels and no-observed-adverse-effect levels. © 2015 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

Psychotic and Bipolar Disorders: Antipsychotic Drugs.

PubMed

Holder, Sarah D; Edmunds, Alaina L; Morgan, Sherri

2017-04-01

Antipsychotic drugs block dopamine receptors and are used to manage psychosis as well as other mental illnesses that may or may not have psychotic features, such as bipolar disorders and major depressive disorder. First-generation antipsychotic drugs are more likely to cause adverse effects such as extrapyramidal symptoms and tardive dyskinesia. Adverse effects of second-generation antipsychotic drugs typically are related to metabolic abnormalities such as weight gain, abnormal blood glucose levels, and elevated lipid levels. Neuroleptic malignant syndrome is a rare but serious adverse effect of antipsychotic drugs that causes mental status changes, hyperthermia, and generalized rigidity. Timely diagnosis is essential due to a high risk of related morbidities if the syndrome remains untreated. Some adverse effects of antipsychotics can be identified and managed so that patients can continue beneficial therapy while minimizing the physiologic consequences. Patients taking antipsychotic drugs should be monitored regularly for adverse effects. Antipsychotics are also associated with potential drug interactions, the most lethal being prolongation of the QT interval, which can lead to fatal arrhythmias. Antipsychotic drugs can be used in special populations, such as pregnant women, children, and elderly patients, per recommendation from a mental health subspecialist. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Examining Differential Resilience Mechanisms by Comparing 'Tipping Points' of the Effects of Neighborhood Conditions on Anxiety by Race/Ethnicity.

PubMed

Coman, Emil Nicolae; Wu, Helen Zhao

2018-02-20

Exposure to adverse environmental and social conditions affects physical and mental health through complex mechanisms. Different racial/ethnic (R/E) groups may be more or less vulnerable to the same conditions, and the resilience mechanisms that can protect them likely operate differently in each population. We investigate how adverse neighborhood conditions (neighborhood disorder, NDis) differentially impact mental health (anxiety, Anx) in a sample of white and Black (African American) young women from Southeast Texas, USA. We illustrate a simple yet underutilized segmented regression model where linearity is relaxed to allow for a shift in the strength of the effect with the levels of the predictor. We compare how these effects change within R/E groups with the level of the predictor, but also how the "tipping points," where the effects change in strength, may differ by R/E. We find with classic linear regression that neighborhood disorder adversely affects Black women's anxiety, while in white women the effect seems negligible. Segmented regressions show that the Ndis → Anx effects in both groups of women appear to shift at similar levels, about one-fifth of a standard deviation below the mean of NDis, but the effect for Black women appears to start out as negative, then shifts in sign, i.e., to increase anxiety, while for white women, the opposite pattern emerges. Our findings can aid in devising better strategies for reducing health disparities that take into account different coping or resilience mechanisms operating differentially at distinct levels of adversity. We recommend that researchers investigate when adversity becomes exceedingly harmful and whether this happens differentially in distinct populations, so that intervention policies can be planned to reverse conditions that are more amenable to change, in effect pushing back the overall social risk factors below such tipping points.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL).

PubMed

Abal, Paula; Louzao, M Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

2017-02-24

Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD 50 ) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard.

Association of PCBs and allergies in children.

PubMed

Tsuji, Mayumi; Kawamoto, Toshihiro; Koriyama, Chihaya; Yamamoto, Megumi; Tsuchiya, Takuto; Matsumura, Fumio

2015-05-01

Recently, the incidence rates of childhood allergies have been rising around the world. The presence of persistent chemical pollutants in the environment and exposure to air pollutants are often cited as potential causes of childhood allergies. Accordingly, epidemiological studies of the associations between exposure to low levels of pollutants and adverse health effects are essential. However, at present no useful biomarkers for evaluating such associations have been developed. Thus, using a molecular epidemiological approach we planned to identify candidate biomarkers of pollutant-induced adverse health effects that can be used in children. In asthmatic children, we found that the serum levels of several polychlorinated biphenyl (PCB) congener sub-types were significantly positively correlated with interleukin (IL)-8 mRNA expression, whereas in a sub-group of children who displayed positive immunoglobulin E (IgE) responses to milk or egg proteins IL-22 mRNA expression was demonstrated to be useful for detecting the adverse health effects of environmental pollutants, particularly PCB congeners. In conclusion, the mRNA expression levels of IL-8 and IL-22 can be used to detect children who are at particular risk of adverse health events caused by environmental pollutants, especially PCBs. Copyright © 2014 Elsevier Inc. All rights reserved.

A preliminary evaluation of sediment quality assessment values for freshwater ecosystems

USGS Publications Warehouse

Smith, Sherri L.; MacDonald, Donald D.; Keenleyside, Karen A.; Ingersoll, Christopher G.; Field, L. Jay

1996-01-01

Sediment quality assessment values were developed using a weight of evidence approach in which matching biological and chemical data from numerous modelling, laboratory, and field studies performed on freshwater sediments were compiled and analyzed. Two assessment values (a threshold effect level (TEL) and a probable effect level(PEL)) were derived for 23 substances, including eight trace metals, six individual polycyclic aromatic hydrocarbons (PAHs), total polychlorinated biphenyls (PCBs), and eight pesticides. The two values defined three ranges of chemical concentrations; those that were (1) rarely, (2) occasionally, and (3) frequently associated with adverse biological effects. An evaluation of the percent incidence of adverse biological effects within the three concentration ranges indicated that the reliability of the TELs (i.e., the degree to which the TELs represent concentrations within the data set below which adverse effects rarely occur) was consistently good. However, this preliminary evaluation indicated that most of the PELs were less reliable (i.e., they did not adequately represent concentrations within the data set above which adverse effects frequently occur). Nonetheless, these values were often comparable to other biological effects-based assessment values (which were themselves reliable), which increased the level of confidence that could be placed in our values. This method is being used as a basis for developing national sediment quality guidelines for freshwater systems in Canada and sediment effect concentrations as part of the Assessment and Remediation of Contaminated Sediments (ARCS) program in the Great Lakes.

“A Modeling Framework for Improved Characterization of Near-Road Air Quality at Fine Scales for Nationwide Exposure Assessment.”

EPA Science Inventory

Communities at the proximity of roadways are exposed to high levels of air pollution from automobile exhaust and are under potential risk of adverse health effects. To understand the relationship between air pollution and adverse health effects, exposure and risk assessment studi...

Health Assessment Document for 1,1,2-Trichloro-1,2,2-Trifluoroethane (Chlorofluorocarbon CFC-113)

EPA Science Inventory

Chlorofluorocarbon 113 (1,1,2-trichloro-1,2,2,-trifluoroethane) has little potential to cause direct adverse health effects at levels found or expected in the general environment (<4.2 ppb). Experimental data do not indicate adverse health effects in humans at a TLV of 1,000 ppm....

Ground experiments for finding principles and working out methods for preventing adverse effects of weightlessness on the human organism

NASA Technical Reports Server (NTRS)

Kakurin, L. I.; Gregoryev, A. I.; Mikhailov, V. M.; Tishler, V. A.

1980-01-01

A comparative assessment of the effectiveness of different prophylactic procedures to prevent the adverse effects of weightlessness is presented. It is concluded that: physical training is most effective but no single method by itself produces the full effect, and an adjustment of regimes to one another enhances the effect. The approved complex of prophylactic procedures affected basic changes occurring in hypokinesia: deficit of muscular activity, no or reduced BP hydrostatic component, reduced volume of blood circulation, reduced hydration level, and the application of various prophylactic complexes during 49 day antiorthostatic hypodynamia eliminated or reduced the adverse effects of weightlessness in simulation.

Impact of early life adversity on EMG stress reactivity of the trapezius muscle

PubMed Central

Luijcks, Rosan; Vossen, Catherine J.; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J.; Lousberg, Richel

2016-01-01

Abstract Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0–11 years) and adolescence (12–17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability. Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies. PMID:27684800

Mechanisms and assessment of statin-related muscular adverse effects

PubMed Central

Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

2014-01-01

Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

Fish oil and olive oil supplements attenuate the adverse cardiovascular effects of concentrated ambient air pollution particles exposure in healthy middle-aged adult human volunteers

EPA Science Inventory

Exposure to ambient levels of air pollution increases cardiovascular morbidity and mortality. Advanced age is among the factors associated with susceptibility to the adverse effects of air pollution. Dietary fatty acid supplementation has been shown to decrease cardiovascular ris...

Health Assessment Document for 1,1,2-Trichloro-1,2,2-Trifluoroethane (Chlorofluorocarbon CFC-113)(Revised External Review Draft)

EPA Science Inventory

Chlorofluorocarbon 113 (1,1,2-trichloro-1,2,2-trifluoroethane) has little potential to cause direct adverse health effects at levels found or expected in the general environment (<4.2 ppb). Experimental data do not indicate adverse health effects in humans at a TLV of 1,000 ppm. ...

Quantitative weight of evidence assessment of higher tier studies on the toxicity and risks of neonicotinoids in honeybees. 4. Thiamethoxam.

PubMed

Stephenson, Gladys L; Solomon, Keith R

2017-01-01

A quantitative weight of evidence (QWoE) methodology was used to assess several higher-tier studies on the effects of thiamethoxam (TMX) on honeybees. Assessment endpoints were population size and viability of commercially managed honeybee colonies and quantity of hive products. A higher-tier field toxicology study indicated a no-observed-adverse effect concentration (NOAEC) of 29.5 µg TMX/kg syrup, equivalent to an oral no-observed-adverse-effect-dose (NOAED) of 8.6 ng/bee/day for all responses measured. For exposures via deposition of dust, a conservative no-observed-adverse-effect-rate at the level of the colony was 0.1 g TMX/ha. There was minimal risk to honeybees from exposure to TMX via nectar and pollen from its use as a seed-treatment. For exposures via dust and dust/seed applications, there were no concentrations above the risk values for TMX in nectar and pollen. Although some risks were identified for potential exposures via guttation fluid, this route of exposure is incomplete; no apparent adverse effects were observed in field studies. For exposures via dust/seed and dust/foliar applications, few adverse effects were observed. Considering all lines of evidence, the quality of the studies included in this analysis was variable. However, the results of the studies were consistent and point to the same conclusion. The overall weight of evidence based on many studies indicates that TMX has no adverse effects on viability or survival of the colony. Thus, the overall conclusion is that the treatment of seeds with thiamethoxam, as currently used in good agricultural practices, does not present a significant risk to honeybees at the level of the colony.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

PubMed Central

Abal, Paula; Louzao, M. Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M.

2017-01-01

Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard. PMID:28245573

Energy drink usage among university students in a Caribbean country: Patterns of use and adverse effects.

PubMed

Reid, Sandra D; Ramsarran, Jonathan; Brathwaite, Rachel; Lyman, Sarika; Baker, Ariane; Cornish, D'Andra C; Ganga, Stefan; Mohammed, Zahrid; Sookdeo, Avinash T; Thapelo, Cathrine K

2015-06-01

There has been little inquiry addressing whether or not concerns about adverse effects of energy drink usage are relevant in the Caribbean. This survey investigated energy drink usage and adverse consequences among tertiary level students in Trinidad and Tobago. A cross-sectional survey of 1994 students from eight institutions was conducted using a de novo questionnaire based on findings from a focus group of students. Chi-squared analyses and logistic regression were used to assess relationships between energy drink usage, adverse effects and other factors affecting energy drink use, and to verify predictors of energy drink use. Prevalence of use was 86%; 38% were current users. Males were more likely to use, used more frequently and at an earlier age. Energy drinks were used most commonly to increase energy (50%), combat sleepiness (45%) and enhance academic performance (40%), and occurred during sports (23%) and mixed with alcohol (22.2%). The majority (79.6%) consumed one energy drink per sitting; 62.2% experienced adverse effects, most commonly restlessness (22%), jolt and crash (17.1%) and tachycardia (16.6%). Awareness of adverse effects was associated with no use (p=0.004), but adverse effects were not a deterrent to continued use. Energy drink usage is prevalent among students. The use is not excessive, but associated with high rates of adverse effects and occurs in potentially dangerous situations like during exercise and with alcohol. There is a need to educate students about the potential adverse effects of energy drinks. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

Childhood Lead Poisoning in the '90s.

ERIC Educational Resources Information Center

Piomelli, Sergio

1994-01-01

Notes that, despite gains in eliminating lead sources, there are still detectable effects from low-level exposure. Discusses at what level of exposure the adverse effects of lead become trivial and what measures, if any, should be taken to reduce low-level exposure. (HTH)

Systematic review of pediatric health outcomes associated with childhood adversity.

PubMed

Oh, Debora Lee; Jerman, Petra; Silvério Marques, Sara; Koita, Kadiatou; Purewal Boparai, Sukhdip Kaur; Burke Harris, Nadine; Bucci, Monica

2018-02-23

Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity. PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers. After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion. Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better understand how adversity, its timing and severity, and the presence of individual genetic, epigenetic, and protective factors affects children's health and development.

Preliminary assessment of the relative toxicity of 1,5-diazido-3-nitrazapentane 90-day dermal application male and female rabbits study number 75-51-y809-90, May 1990 - June 1992. Phase 2. Final report, May 1990-June 1992

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

Haight, E.A.; Harvey, J.G.; Beall, P.

1992-06-01

A 90-day application of DANPE has the potential to cause testicular hypospermatogenesis in male rabbits and an apparent inhibition of mature ovarian follicles formation in female rabbits. A no-observed-adverse-effect-level was not achieved in the male rabbits but was achieved in female rabbits at 27.3 mg/kg dose level.... 1,5-Diazido-3-Nitrazapentane, Dermal, Approximate Lethal Dose (ALD), Testicular hypospermatogenesis, Ovarian follicle No-observed-adverse-effect-level (NOAEL).

Influence of total face, facial and nasal masks on short-term adverse effects during noninvasive ventilation.

PubMed

Holanda, Marcelo Alcantara; Reis, Ricardo Coelho; Winkeler, Georgia Freire Paiva; Fortaleza, Simone Castelo Branco; Lima, José Wellington de Oliveira; Pereira, Eanes Delgado Barros

2009-02-01

Failure of noninvasive ventilation (NIV) has been associated with short-term adverse effects related to the use of masks. The aim of this study was to compare the incidence, type and intensity of adverse effects, as well as the comfort, of total face masks (TFMs), facial masks (FMs) and nasal masks (NMs) during NIV. This was a randomized crossover trial involving 24 healthy volunteers submitted to six sessions of NIV in bilevel positive airway pressure mode using the TFM, FM and NM masks at low and moderate-to-high pressure levels. A written questionnaire was applied in order to evaluate eleven specific adverse effects related to the use of the masks. Comfort was assessed using a visual analog scale. The CO2 exhaled into the ventilator circuit was measured between the mask and the exhalation port. The performance of the TFM was similar to that of the NM and FM in terms of comfort scores. Higher pressure levels reduced comfort and increased adverse effects, regardless of the mask type. When the TFM was used, there were fewer air leaks and less pain at the nose bridge, although there was greater oronasal dryness and claustrophobia. Air leaks were most pronounced when the FM was used. The partial pressure of exhaled CO2 entering the ventilator circuit was zero for the TFM. The short-term adverse effects caused by NIV interfaces are related to mask type and pressure settings. The TFM is a reliable alternative to the NM and FM. Rebreathing of CO2 from the circuit is less likely to occur when a TFM is used.

The Effect of IQ Level on the Degree of Cognitive Deterioration Experienced during Acute Hypoglycemia in Normal Humans.

ERIC Educational Resources Information Center

Gold, Ann E.; And Others

1995-01-01

Whether IQ level exerts a differential effect on the impairment of cognitive performance induced during acute hypoglycemia was studied for 24 nondiabetic adults. At various levels of hypoglycemia, no overall effect of IQ on deterioration was noted. Higher IQ did not apparently protect against adverse effects. (SLD)

Germline glutathione S-transferase variants in breast cancer: Relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy

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

Edvardsen, Hege; Kristensen, Vessela N.; Medical Faculty, University of Oslo, Oslo

Purpose: To explore whether certain glutathione S-transferase (GST) polymorphisms are associated with an increased risk of breast cancer or the level of radiation-induced adverse effects after two fractionation patterns of adjuvant radiotherapy. Methods and Materials: The prevalence of germline polymorphic variants in GSTM1, GSTP1, and GSTT1 was determined in 272 breast cancer patients and compared with that in a control group of 270 women from the general population with no known history of breast cancer. The genetic variants were determined using multiplex polymerase chain reaction followed by restriction enzyme fragment analysis. In 253 of the patients surveyed for radiotherapy-induced sidemore » effects after a median observation time of 13.7 years (range, 7-22.8 years), the genotypes were related to the long-term effects observed after two fractionation patterns (treatment A, 4.3 Gy in 10 fractions for 156 patients; and treatment B, 2.5 Gy in 20 fractions for 97; both administered within a 5-week period). Results: None of the GST polymorphisms conferred an increased risk of breast cancer, either alone or in combination. Compared with treatment B, treatment A was followed by an increased level of moderate to severe radiation-induced side effects for all the endpoints studied (i.e., degree of telangiectasia, subcutaneous fibrosis and atrophy, lung fibrosis, costal fractures, and pleural thickening; p <0.001 for all endpoints). A significant association was found between the level of pleural thickening and the GSTP1 Ile105Val variant. Conclusion: The results of this study have illustrated the impact of hypofractionation on the level of adverse effects and indicated that the specific alleles of GSTP1, M1, and T1 studied here may be significant in determining the level of adverse effects after radiotherapy.« less

Adverse effects of microplastics and oxidative stress-induced MAPK/Nrf2 pathway-mediated defense mechanisms in the marine copepod Paracyclopina nana

PubMed Central

Jeong, Chang-Bum; Kang, Hye-Min; Lee, Min-Chul; Kim, Duck-Hyun; Han, Jeonghoon; Hwang, Dae-Sik; Souissi, Sami; Lee, Su-Jae; Shin, Kyung-Hoon; Park, Heum Gi; Lee, Jae-Seong

2017-01-01

Microplastic pollution causes a major concern in the marine environment due to their worldwide distribution, persistence, and adverse effects of these pollutants in the marine ecosystem. Despite its global presence, there is still a lack of information on the effect of microplastics on marine organisms at the molecular level. Herein we demonstrated ingestion and egestion of nano- (0.05 μm) and micro-sized (0.5 and 6 μm) polystyrene microbeads in the marine copepod Paracyclopina nana, and examined molecular responses to exposure to microbeads with in vivo endpoints such as growth rate and fecundity. Also, we proposed an adverse outcome pathway for microplastic exposure that covers molecular and individual levels. This study provides the first insight into the mode of action in terms of microplastic-induced oxidative stress and related signaling pathways in P. nana. PMID:28117374

Adverse effects of microplastics and oxidative stress-induced MAPK/Nrf2 pathway-mediated defense mechanisms in the marine copepod Paracyclopina nana

NASA Astrophysics Data System (ADS)

Jeong, Chang-Bum; Kang, Hye-Min; Lee, Min-Chul; Kim, Duck-Hyun; Han, Jeonghoon; Hwang, Dae-Sik; Souissi, Sami; Lee, Su-Jae; Shin, Kyung-Hoon; Park, Heum Gi; Lee, Jae-Seong

2017-01-01

Microplastic pollution causes a major concern in the marine environment due to their worldwide distribution, persistence, and adverse effects of these pollutants in the marine ecosystem. Despite its global presence, there is still a lack of information on the effect of microplastics on marine organisms at the molecular level. Herein we demonstrated ingestion and egestion of nano- (0.05 μm) and micro-sized (0.5 and 6 μm) polystyrene microbeads in the marine copepod Paracyclopina nana, and examined molecular responses to exposure to microbeads with in vivo endpoints such as growth rate and fecundity. Also, we proposed an adverse outcome pathway for microplastic exposure that covers molecular and individual levels. This study provides the first insight into the mode of action in terms of microplastic-induced oxidative stress and related signaling pathways in P. nana.

A review and rationale for studying the cardiovascular effects of drinking water arsenic in women of reproductive age

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

Kwok, Richard K., E-mail: rkwok@rti.org

2007-08-01

Drinking water arsenic has been shown to be associated with a host of adverse health outcomes at exposure levels > 300 {mu}g of As/L. However, the results are not consistent at exposures below this level. We have reviewed selected articles that examine the effects of drinking water arsenic on cardiovascular outcomes and present a rationale for studying these effects on women of reproductive age, and also over the course of pregnancy when they would potentially be more susceptible to adverse cardiovascular and reproductive outcomes. It is only recently that reproductive effects have been linked to drinking water arsenic. However, theremore » is a paucity of information about the cardiovascular effects of drinking water arsenic on women of reproductive age. Under the cardiovascular challenge of pregnancy, we hypothesize that women with a slightly elevated exposure to drinking water arsenic may exhibit adverse cardiovascular outcomes at higher rates than in the general population. Studying sensitive clinical and sub-clinical indicators of disease in susceptible sub-populations may yield important information about the potentially enormous burden of disease related to low-level drinking water arsenic exposure.« less

Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study.

PubMed

Tabara, Yasuharu; Takahashi, Yoshimitsu; Setoh, Kazuya; Kawaguchi, Takahisa; Gotoh, Norimoto; Terao, Chikashi; Yamada, Ryo; Kosugi, Shinji; Sekine, Akihiro; Nakayama, Takeo; Matsuda, Fumihiko

2016-01-01

Previous studies have reported that artificial increases in circulating free fatty acid (FFA) levels might have adverse effects on the vasculature. However, whether or not this effect can be extrapolated to physiological variations in FFA levels has not been clarified. Given that FFAs exert a lipotoxic effect on pancreatic β-cells and might directly damage the arterial endothelium, we hypothesized that these adverse effects might synergize with hyperglycemia. A total of 9396 Japanese subjects were included in the study. Serum FFA levels were measured at baseline examination. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. As serum levels of FFA were markedly lower in subjects with higher insulin level, a significant association between FFA levels and baPWV was observed only in subjects with blood samples taken under fasting (≥12 h, P<0.001) or near-fasting (5-11 h, P<0.001) conditions, and not in those taken under non-fasting (<5 h, P=0.307) conditions. Although type 2 diabetes and HbA1c showed a strong association with baPWV, the association between FFA level and baPWV remained significant (β=0.052, P<0.001) after adjustment for glycemic levels. In addition to their direct relationship, FFA and glucose levels were synergistically associated with baPWV (FFA(⁎)glucose; β=0.036, P<0.001). Differences in baPWV between the lowest and highest subgroups divided by a combination of FFA and glucose reached approximately 300 cm/s. Physiological variations in FFA concentrations might be a risk factor for large arterial stiffness. FFA and hyperglycemia exert a synergistic adverse effect on the vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone.

PubMed

Kim, Jong-Hoon; Kim, Min-Jung

2009-01-01

The purpose of the present study was to examine the association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone. Thirty outpatients with schizophrenia receiving stable doses of risperidone were comprehensively evaluated for psychopathology, subjective well-being, and adverse drug effects. Subjective well-being was assessed using the Subjective Well-being Under Neuroleptics Scale (SWN). Adverse drug effects were evaluated using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). In correlation analysis controlling for relevant variables, the SWN score had significant negative correlations with the following subscale scores of the LUNSERS: extrapyramidal side effect (EPS) (r = -0.54, P < 0.01), akathisia (r = -0.46, P < 0.05), and autonomic adverse effect (r = -0.44, P < 0.05). The SWN score also had a significant negative correlation with the global severity of EPS as measured by the DIEPSS (r = -0.44, P < 0.05). The results of our study suggest that adverse effects, particularly EPS and akathisia, are significantly associated with subjective well-being, implying the necessity to develop rational strategies to control these variables effectively. The results also suggest that EPS and akathisia continue to be major adverse effects associated with a low level of subjective well-being in patients receiving risperidone. Further studies are required to investigate the multidimensional factors associated with subjective well-being in patients receiving atypical antipsychotics and to determine their relative contributions.

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. © The Author (2015). Published by Oxford University Press.

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

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia

PubMed Central

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

Background While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012–2013. Methods The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Findings Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Conclusions Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control. PMID:28339462

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia.

PubMed

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013. The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.

Changing social factors and their long-term implications for health.

PubMed

Wadsworthx, M E

1997-01-01

This paper presents findings and arguments to show the power of social factors to affect health at the individual and at the national level. Social factors most strongly and negatively associated with health, at both levels, are those that indicate disorganisation and disruption, perceived helplessness and lack of support, low educational attainment, and poverty. Adverse changes in these social factors and their negative effects on health have been observed in many studies. When such adverse changes affect the lives and health of children, and those who will become parents, they affect the present and long-term future health of individuals because of the processes of biological programming described in this and other papers presented here. Such adverse changes in social factors also adversely affect the social circumstances of childhood, which in turn have a negative impact on health. Because changing social factors affect biological programming and social capitalisation, awareness of the health damaging effects of recent social change provides information on the future health of the population.

Circumpolar contaminant concentrations in polar bears (Ursus maritimus) and potential population-level effects.

PubMed

Nuijten, R J M; Hendriks, A J; Jenssen, B M; Schipper, A M

2016-11-01

Polar bears (Ursus maritimus) currently receive much attention in the context of global climate change. However, there are other stressors that might threaten the viability of polar bear populations as well, such as exposure to anthropogenic pollutants. Lipophilic organic compounds bio-accumulate and bio-magnify in the food chain, leading to high concentrations at the level of top-predators. In Arctic wildlife, including the polar bear, various adverse health effects have been related to internal concentrations of commercially used anthropogenic chemicals like PCB and DDT. The extent to which these individual health effects are associated to population-level effects is, however, unknown. In this study we assembled data on adipose tissue concentrations of ∑PCB, ∑DDT, dieldrin and ∑PBDE in individual polar bears from peer-reviewed scientific literature. Data were available for 14 out of the 19 subpopulations. We found that internal concentrations of these contaminants exceed threshold values for adverse individual health effects in several subpopulations. In an exploratory regression analysis we identified a clear negative correlation between polar bear population density and sub-population specific contaminant concentrations in adipose tissue. The results suggest that adverse health effects of contaminants in individual polar bears may scale up to population-level consequences. Our study highlights the need to consider contaminant exposure along with other threats in polar bear population viability analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Preadoption adversity, MAOA, and behavioral adjustment in internationally adopted Chinese girls.

PubMed

Li, Jun; Tan, Tony Xing; Camras, Linda A; Chen, Chuansheng; Moyzis, Robert K

2014-10-01

We studied postinstitutionalized adopted Chinese girls to determine whether those with different variants of the MAOA gene promoter region (MAOA-VNTR) differed in their internalizing and externalizing behavior problems and whether the MAOA genotype moderated the relation between preadoption adversity and current behavior problems. MAOA genotyping was obtained for 94 girls (mean age: 9.2 years) and the number of 4-repeat (4R) alleles was determined (zero, one, or two). The adoptive mothers rated several indicators of preadoption adversity shortly after adoption (mean age at adoption 15.8 months) and completed the Child Behavior Checklist when the children were 8.1 years on average. No main effects were found for preadoption adversity. However, the MAOA genotype had a nominally significant effect (P<0.05) on internalizing problems. Regression analyses controlling for age, household income, authoritarian parenting, and family problems showed that among children with no physical signs of preadoption adversity, those carrying a greater number of 4R alleles scored significantly lower (P<0.01) on internalizing problems than those with fewer 4R alleles. Differences in internalizing scores related to the MAOA genotype were not observed for children who showed one or more physical signs of adversity at the time of adoption. A similar pattern was found for externalizing problems, although the results did not reach conventional levels of significance. Our results suggest that higher MAOA activity may be protective with respect to internalizing problems in internationally adopted Chinese girls, but that this protective effect decreases at higher levels of preadoption adversity. A similar pattern may exist for externalizing problems.

The impact of social cognitive variables on the initial level of depression and recovery.

PubMed

Lam, D H; Green, B; Power, M J; Checkley, S

1994-10-01

Thirty-seven patients who fulfilled DSM-III-R criteria for Major Depressive Disorder were recruited for a double-blind controlled trial of Desipramine and placebo for 6 weeks. Data about social cognitive variables, including social adversities, investment in roles and goals, general social support and crisis support were collected. Crisis support had a moderating effect on the initial level of depression: the more crisis support the subjects had, the less depressed they were on recruitment. Initial level of depression, the experience of adversity and drugs all contributed significantly to recovery defined as Hamilton Rating for Depression less than 10 at week 6. When recovery was defined as Hamilton score halved or more than halved between week 2 and week 6, subjects' level of ideal emotional support, and whether they had experienced adversity in their most invested domains, contributed significantly to recovery, independent of any drug effects or the initial level of depression. The higher their level of ideal emotional support, the less was the chance of these subjects recovering. The findings of this study pointed to the importance of controlling for psycho-social variables in studies of response to treatment.

Predictive value of self-stigma, insight, and perceived adverse effects of medication for the clinical outcomes in patients with depressive disorders.

PubMed

Yen, Cheng-Fang; Lee, Yu; Tang, Tze-Chun; Yen, Ju-Yu; Ko, Chih-Hung; Chen, Cheng-Chung

2009-03-01

The aims of this prospective study were to examine the predictive values of self-stigma, insight, and perceived adverse effects of medication for remission of depressive symptoms, suicidal risk, and medication adherence in patients with depressive disorders over a 1-year follow-up period. One hundred seventy-four participants who were in a state of obvious depression underwent an index interview to determine their degree of self-stigma, insight, and perceived adverse effects of medication. One year later, they were reassessed to determine the severity of their depressive symptoms, suicidal risk, and the level of the medication adherence, and their associations with the 3 possible predictors at the index interview were examined. The results of this study indicated that perceiving more severe adverse effects of medication at the index interview increased the risks of the nonremission of depressive symptoms, occurrence of suicidal ideation or attempt, and medication nonadherence in patients with depressive disorders in the 1-year period. However, the degrees of self-stigma and insight did not predict the severity of depressive symptoms, suicidal risk, or the level of the medication adherence. Based on the results of this study, we suggest that it is important for clinicians to prevent the occurrence of and to help patients manage the adverse effects of medication. We also suggest that further prospective studies are needed to examine the predictive values of self-stigma and insight for clinical outcomes and medication adherence.

The cost of nurse-sensitive adverse events.

PubMed

Pappas, Sharon Holcombe

2008-05-01

The aim of this study was to describe the methodology for nursing leaders to determine the cost of adverse events and effective levels of nurse staffing. The growing transparency of quality and cost outcomes motivates healthcare leaders to optimize the effectiveness of nurse staffing. Most hospitals have robust cost accounting systems that provide actual patient-level direct costs. These systems allow an analysis of the cost consumed by patients during a hospital stay. By knowing the cost of complications, leaders have the ability to justify the cost of improved staffing when quality evidence shows that higher nurse staffing improves quality. An analysis was performed on financial and clinical data from hospital databases of 3,200 inpatients. The purpose was to establish a methodology to determine actual cost per case. Three diagnosis-related groups were the focus of the analysis. Five adverse events were analyzed along with the costs. A regression analysis reported that the actual direct cost of an adverse event was dollars 1,029 per case in the congestive heart failure cases and dollars 903 in the surgical cases. There was a significant increase in the cost per case in medical patients with urinary tract infection and pressure ulcers and in surgical patients with urinary tract infection and pneumonia. The odds of pneumonia occurring in surgical patients decreased with additional registered nurse hours per patient day. Hospital cost accounting systems are useful in determining the cost of adverse events and can aid in decision making about nurse staffing. Adverse events add costs to patient care and should be measured at the unit level to adjust staffing to reduce adverse events and avoid costs.

Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects☆☆☆

PubMed Central

Tedesco, Ana Paula; Martins, Juliana Saccol; Nicolini-Panisson, Renata D’Agostini

2014-01-01

Objective To report on the experience of injections of botulinum toxin A (BTA) in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS) level V. Methods This was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations), in which the basic aim was to look for adverse effects. Results The mean number of application sessions per patient was three, and the mean age at the time of each injection was 4 + 6 years (range: 1.6–13 years). The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month. Conclusion The absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia. PMID:26229827

A review of low-level air pollution and adverse effects on human health: implications for epidemiological studies and public policy

PubMed Central

Olmo, Neide Regina Simões; do Nascimento Saldiva, Paulo Hilário; Braga, Alfésio Luís Ferreira; Lin, Chin An; de Paula Santos, Ubiratan; Pereira, Luiz Alberto Amador

2011-01-01

The aim of this study was to review original scientific articles describing the relationship between atmospheric pollution and damage to human health. We also aimed to determine which of these studies mentioned public policy issues. Original articles relating to atmospheric pollution and human health published between 1995 and 2009 were retrieved from the PubMed database and analyzed. This study included only articles dealing with atmospheric pollutants resulting primarily from vehicle emissions. Three researchers were involved in the final selection of the studies, and the chosen articles were approved by at least two of the three researchers. Of the 84 non-Brazilian studies analyzed, 80 showed an association between atmospheric pollution and adverse effects on human health. Moreover, 66 showed evidence of adverse effects on human health, even at levels below the permitted emission standards. Three studies mentioned public policies aimed at changing emission standards. Similarly, the 29 selected Brazilian studies reported adverse associations with human health, and 27 showed evidence of adverse effects even at levels below the legally permitted emission standards. Of these studies, 16 mentioned public policies aimed at changing emission standards. Based on the Brazilian and non-Brazilian scientific studies that have been conducted, it can be concluded that, even under conditions that are compliant with Brazilian air quality standards, the concentration of atmospheric pollutants in Brazil can negatively affect human health. However, as little discussion of this topic has been generated, this finding demonstrates the need to incorporate epidemiological evidence into decisions regarding legal regulations and to discuss the public policy implications in epidemiological studies. PMID:21655765

Management of common adverse effects in the era of highly active antiretroviral therapy in south east Ethiopia

PubMed Central

Abdella, Sadikalmahdi Hussen; Wabe, Nasir Tajure; Yesuf, Elias Ali

2011-01-01

Background: The combination of antiretroviral therapy is the corner stone of management of patients with human immune deficiency virus infection. Although antiretroviral therapy can reduce viral load to undetectable level, improve the immunity and prolong survival of patients, antiretroviral drugs are associated with many adverse effects that may be severe and affect patient adherence and quality of life. Aims: The aim of this study was to assess management strategies under taken in patient's experienced common adverse effects of highly active antiretroviral therapy in Goba Hospital antiretroviral clinic. Patients and Methods: A cross sectional study of patient record chart of patients who had follow-up during data collection period was done followed by patient interview. Data was filled on well structured questionnaire and analyzed using SPSS for window version 16.0. Results: The common adverse effects were Rash (48.8%), Peripheral neuropathy (36.9%) and Anemia (20.24%). The rate of management was 39.3%. Pyridoxine (36.8%) was commonly prescribed drug for management of Peripheral neuropathy. Chlorphenarimine gel and Iron gluconate were common drugs for management of Rash and Anemia respectively. Use of traditional healers (57.7%) was leading reason for non-management. Conclusion: Rate of management for common adverse effect is low. Education should be given on adverse effects for patients. PMID:22361495

Effects of febuxostat on serum urate level in Japanese hyperuricemia patients.

PubMed

Yamamoto, Tetsuya; Hidaka, Yuji; Inaba, Masaaki; Ishimura, Eiji; Ooyama, Hiroshi; Kakuda, Hirokazu; Moriwaki, Yuji; Higami, Kenshi; Ohtawara, Akira; Hosoya, Tatsuo; Nishikawa, Hazime; Taniguchi, Atsuo; Ueda, Takanori; Yamauchi, Takahiro; Fujimori, Shin; Mineo, Ikuo; Yamanaka, Hisashi

2015-09-01

We assessed the efficacy and adverse effects of febuxostat in male hyperuricemia patients. This was a 12-week, multicenter, open-label, uncontrolled study. The enrolled subjects were 89 hyperuricemic male patients (12 overexcretors, 56 normal excretors, and 21 underexcretors). The endpoint was percent change in serum urate level. The concentration of urate in serum before and 12 weeks after beginning administration of febuxostat in the overexcretors was 9.34 ± 1.48 and 5.59 ± 1.17 mg/dl, respectively, while those were 8.59 ± 1.24 and 5.41 ± 1.35 mg/dl, respectively, in the normal excretors, and 8.29 ± 1.01and 5.11 ± 1.71 mg/dl, respectively, in the underexcretors. After 12 weeks, the rate of change in serum urate after beginning administration of febuxostat was - 0.384 ± 0.186 in the overexcretors, - 0.368 ± 0.128 in the normal excretors, and - 0.365 ± 0.217 in the underexcretors, with no significant differences among them. A common adverse event related to febuxostat was gout flare. Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.

APPROACHES TO EXTRAPOLATING EFFECTS OF EDCS ACROSS BIOLOGICAL LEVELS OF ORGANIZATION IN FISH

EPA Science Inventory

A challenge in ecological risk assessments is to obtain, in a resource-effective manner, information that provides insight both into chemical mode/mechanism of action (MOA) and adverse effects in individual animals, which are indicative of potential population-level responses. T...

Comparing the Effectiveness and Safety of the Addition of and Switching to Aripiprazole for Resolving Antipsychotic-Induced Hyperprolactinemia: A Multicenter, Open-Label, Prospective Study.

PubMed

Yoon, Hui Woo; Lee, Jung Suk; Park, Sang Jin; Lee, Seon-Koo; Choi, Won-Jung; Kim, Tae Yong; Hong, Chang Hyung; Seok, Jeong-Ho; Park, Il-Ho; Son, Sang Joon; Roh, Daeyoung; Kim, Bo-Ra; Lee, Byung Ook

Hyperprolactinemia is an important but often overlooked adverse effect of antipsychotics. Several studies have shown that switching to or adding aripiprazole normalizes antipsychotic-induced hyperprolactinemia. However, no study has directly compared the effectiveness and safety of the 2 strategies. A total of 52 patients with antipsychotic-induced hyperprolactinemia were recruited. Aripiprazole was administered to patients with mild hyperprolactinemia (serum prolactin level < 50 ng/mL). Patients with severe hyperprolactinemia (serum prolactin level > 50 ng/mL) were randomized to an aripiprazole-addition group (adding aripiprazole to previous antipsychotics) or a switching group (switching previous antipsychotics to aripiprazole). Serum prolactin level, menstrual disturbances, sexual dysfunction, psychopathologies, and quality of life were measured at weeks 0, 1, 2, 4, 6, and 8. Both the addition and switching groups showed significantly reduced serum prolactin level and menstrual disturbances and improved sexual dysfunction. In patients with severe hyperprolactinemia, the numbers of patients with hyperprolactinemia and menstrual disturbance in the switching group were significantly lower than those in the addition group at week 8. Both the addition and switching strategies were effective in resolving antipsychotic-induced hyperprolactinemia and hyperprolactinemia-related adverse events, including menstrual disturbances and sexual dysfunction. In addition, these findings suggest that switching to aripiprazole may be more effective than addition of aripiprazole for normalizing hyperprolactinemia and improving hyperprolactinemia-related adverse events in patients with schizophrenia.

Stress in 1st-year women teachers: the context of social support and coping.

PubMed

Schonfeld, I S

2001-05-01

The effects of adverse work environments were examined in the context of other risk/protective factors in this extension of a short-term longitudinal study involving 184 newly appointed women teachers. Regression analyses revealed that-adjusting for preemployment levels of the outcomes and negative affectivity-social support and adversity in the fall work environment were among the factors that affected spring depressive symptoms, self-esteem, job satisfaction, and motivation to teach. Support from nonwork sources was directly related to future improved symptom levels and self-esteem; supervisor and colleague support were directly related to future job satisfaction. Effects of occupational coping, professional efficacy, locus of control, and school factors (e.g., special vs. regular education) were largely nonsignificant. Structural equation analyses indicated that adverse working conditions began to seriously affect the women soon after they started teaching.

Modeling a molecular initiating event to population effects: A case study of aromatase inhibition in fathead minnows

EPA Science Inventory

An adverse outcome pathway (AOP) conceptually links a molecular initiating event with measureable key events at higher levels of biological organization that ultimately result in an adverse outcome. Development of an AOP requires experimental data and scientific expertise to ide...

Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

EPA Science Inventory

Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

Dredging Research: Information from the Engineer Research and Development Center. Volume 7, Number 1. Corps Education Center a Big Success

DTIC Science & Technology

2004-03-01

likeli- hood of adverse effects. UDMEED contains ecotoxico - logical and reference data relevant to assessing the potential for impacts of concern...The effects data have been translated into ecotoxico - logical endpoints, such as “No Observed Adverse Ecological Effect Level (NOAEL),” “Lethal...ited in an upland situation, several broad taxonomic categories, and various contaminants (e.g., bio- accumulation and plants and metals ; or toxicity

Lessons learnt from Dental Patient Safety Case Reports

PubMed Central

Obadan, Enihomo M.; Ramoni, Rachel B.; Kalenderian, Elsbeth

2015-01-01

Background Errors are commonplace in dentistry, it is therefore our imperative as dental professionals to intercept them before they lead to an adverse event, and/or mitigate their effects when an adverse event occurs. This requires a systematic approach at both the profession-level, encapsulated in the Agency for Healthcare Research and Quality’s Patient Safety Initiative structure, as well as at the practice-level, where Crew Resource Management is a tested paradigm. Supporting patient safety at both the dental practice and profession levels relies on understanding the types and causes of errors, an area in which little is known. Methods A retrospective review of dental adverse events reported in the literature was performed. Electronic bibliographic databases were searched and data were extracted on background characteristics, incident description, case characteristics, clinic setting where adverse event originated, phase of patient care that adverse event was detected, proximal cause, type of patient harm, degree of harm and recovery actions. Results 182 publications (containing 270 cases) were identified through our search. Delayed and unnecessary treatment/disease progression after misdiagnosis was the largest type of harm reported. 24.4% of reviewed cases were reported to have experienced permanent harm. One of every ten case reports reviewed (11.1%) reported that the adverse event resulted in the death of the affected patient. Conclusions Published case reports provide a window into understanding the nature and extent of dental adverse events, but for as much as the findings revealed about adverse events, they also identified the need for more broad-based contributions to our collective body of knowledge about adverse events in the dental office and their causes. Practical Implications Siloed and incomplete contributions to our understanding of adverse events in the dental office are threats to dental patients’ safety. PMID:25925524

Proposed Methodology for Specifying Atrazine Levels of Concern for Protection of Plant Communities in Freshwater Ecosystems

EPA Science Inventory

This document describes a proposed methodology for setting levels of concern (LOCs) for atrazine in natural freshwater systems to prevent unacceptably adverse effects on the aquatic plant communities in those systems. LOCs regarding effects on humans and possible effects on amph...

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Warnings of adverse side effects can backfire over time.

PubMed

Steinhart, Yael; Carmon, Ziv; Trope, Yaacov

2013-09-01

Warnings that a promoted product can have adverse side effects (e.g., smoking cigarettes can cause cancer) should dampen the product's allure. We predicted that with temporal distance (e.g., when an ad relates to future consumption or was viewed some time earlier), this common type of warning can have a worrisome alternative consequence: It can ironically boost the product's appeal. Building on construal-level theory, we argue that this is because temporal distance evokes high-level construal, which deemphasizes side effects and emphasizes message trustworthiness. In four studies, we demonstrated this phenomenon. For example, participants could buy cigarettes or artificial sweeteners after viewing an ad promoting the product. Immediately afterward, the quantity that participants bought predictably decreased if the ad they saw included a warning about adverse side effects. With temporal distance (product to be delivered 3 months later, or 2 weeks after the ad was viewed), however, participants who had seen an ad noting the benefits of the product but warning of risky side effects bought more than those who had seen an ad noting only benefits.

Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs.

PubMed

Parmar, Jayesh R; Forrest, Benjamin D; Freeman, Robert A

2016-01-01

The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory related adverse effects. Finally, insufficient higher-order evidence to support the widespread use of medical marijuana was found, but a limited amount of moderate-level evidence supports its use in pain and seizure management. Published by Elsevier Inc.

Occupational exposure to ultrafine particles in police officers: no evidence for adverse respiratory effects.

PubMed

Jordakieva, G; Grabovac, I; Valic, E; Schmidt, K E; Graff, A; Schuster, A; Hoffmann-Sommergruber, K; Oberhuber, C; Scheiner, O; Goll, A; Godnic-Cvar, J

2018-01-01

Inhalation exposure to fine and ultrafine particles (UFPs) has been associated with respiratory diseases. However, little is known on the quality, threshold levels and concentration of these particles causing adverse health effects. The impact of occupational exposure to submicrometer and UFPs was assessed in 30 healthy police shooting instructors by clinical investigation, self-assessment questionnaire, sputum and spirometry and compared to a control group. General laboratory chemistry parameters, circulating cytokines (interleukin [IL]-2, IL-4, IL-5, IL-6, IL-8, interferon-gamma [IFN-γ]), and granulocyte macrophage colony-stimulating factor (GM-CSF) in serum were measured. UFP exposure was recorded by Scanning Mobility Particle Sizer. Concentrations of submicrometer sized airborne particles (< 700 nm) measured between 3.34 × 10 5 /cm 3 and 7.58 × 10 5 /cm 3 at shooting sites, with highest concentrations found in the UFP range (< 100 nm). The size of the monodispersed particles ranged from 54.74 ± 16.25 nm to 98.19 ± 22.83 nm. Short term exposure (4 h) to high levels of UFPs caused an increase of IFN-γ in exposed subjects ( p  = 0.022). 24 h after exposure a significant decrease of IgG, albumin fibrinogen and factor VII was found. Neither directly after 4 h of high levels UFPs exposure nor 24 h after exposure subjective complaints or objective measurements indicating adverse respiratory effects in exposed subjects were found. No consistent indications for adverse respiratory or inflammatory effects directly following exposure and 24 h after exposure to high levels of UFPs in our study group were detected. However we showed the assessment of short-term exposure effects at a genuine occupational setting, which might is relevant when a risk assessment of high level occupational exposures to UFPs is considered.

A hierarchical modeling approach to estimate regional acute health effects of particulate matter sources

PubMed Central

Krall, J. R.; Hackstadt, A. J.; Peng, R. D.

2017-01-01

Exposure to particulate matter (PM) air pollution has been associated with a range of adverse health outcomes, including cardiovascular disease (CVD) hospitalizations and other clinical parameters. Determining which sources of PM, such as traffic or industry, are most associated with adverse health outcomes could help guide future recommendations aimed at reducing harmful pollution exposure for susceptible individuals. Information obtained from multisite studies, which is generally more precise than information from a single location, is critical to understanding how PM impacts health and to informing local strategies for reducing individual-level PM exposure. However, few methods exist to perform multisite studies of PM sources, which are not generally directly observed, and adverse health outcomes. We developed SHARE, a hierarchical modeling approach that facilitates reproducible, multisite epidemiologic studies of PM sources. SHARE is a two-stage approach that first summarizes information about PM sources across multiple sites. Then, this information is used to determine how community-level (i.e. county- or city-level) health effects of PM sources should be pooled to estimate regional-level health effects. SHARE is a type of population value decomposition that aims to separate out regional-level features from site-level data. Unlike previous approaches for multisite epidemiologic studies of PM sources, the SHARE approach allows the specific PM sources identified to vary by site. Using data from 2000–2010 for 63 northeastern US counties, we estimated regional-level health effects associated with short-term exposure to major types of PM sources. We found PM from secondary sulfate, traffic, and metals sources was most associated with CVD hospitalizations. PMID:28098412

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. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

76 FR 77703 - Hexythiazox; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... the relationship of the results of the studies to human risk. EPA has also considered available... effects including potential carcinogenicity of hexythiazox. Specific information on the studies received...-level (NOAEL) and the lowest-observed-adverse-effect- level (LOAEL) from the toxicity studies can be...

Adapting the Patient-Centered Medical Home to Address Psychosocial Adversity: Results of a Qualitative Study.

PubMed

Vu, Cecilia; Rothman, Emily; Kistin, Caroline J; Barton, Kelly; Bulman, Barb; Budzak-Garza, Ann; Olson-Dorff, Denyse; Bair-Merritt, Megan H

The patient-centered medical home (PCMH) seeks to improve population health. However, PCMH models often focus on improving treatment of chronic diseases rather than on addressing psychosocial adversity. We sought to gather key stakeholder input about how PCMHs might feasibly and sustainably address psychosocial adversity within their patient populations. We conducted 25 semistructured interviews with key stakeholders, such as physicians, nurses, medical assistants, and patients. The audiorecorded interviews focused on participants' perceptions of the best ways to modify the PCMH to address patients' psychosocial adversity. To facilitate information gathering, a fictional patient case was presented. Analyses were conducted using a 3-stage content-analysis process. Participants identified provider-related and systems-level changes necessary for addressing these psychosocial adversities effectively. On the provider level, participants thought that practitioners should foster trusting relationships with patients and should be emotionally present as patients describe their life experiences. Participants also emphasized that providers need to have sensitive conversations about adversity and resilience. On a systems level, participants discussed that documentation must balance privacy and include relevant information in the medical record. In addition, care should be delivered not by a single provider but by a team that has a longitudinal relationship with the patient; this care team should include behavioral health support. Participants provided practical strategies and highlighted provider and systems level changes to adequately address patients' prior psychosocial adversity. Future studies need to assess the degree to which such a trauma-informed approach improves patient access, outcomes, and care quality, and reduces cost. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Mining Adverse Events of Dietary Supplements from Product Labels by Topic Modeling.

PubMed

Wang, Yefeng; Gunashekar, Divya R; Adam, Terrence J; Zhang, Rui

2017-01-01

The adverse events of the dietary supplements should be subject to scrutiny due to their growing clinical application and consumption among U.S. adults. An effective method for mining and grouping the adverse events of the dietary supplements is to evaluate product labeling for the rapidly increasing number of new products available in the market. In this study, the adverse events information was extracted from the product labels stored in the Dietary Supplement Label Data-base (DSLD) and analyzed by topic modeling techniques, specifically Latent Dirichlet Allocation (LDA). Among the 50 topics generated by LDA, eight topics were manually evaluated, with topic relatedness ranging from 58.8% to 100% on the product level, and 57.1% to 100% on the ingredient level. Five out of these eight topics were coherent groupings of the dietary supplements based on their adverse events. The results demonstrated that LDA is able to group supplements with similar adverse events based on the dietary supplement labels. Such information can be potentially used by consumers to more safely use dietary supplements.

Mining Adverse Events of Dietary Supplements from Product Labels by Topic Modeling

PubMed Central

Wang, Yefeng; Gunashekar, Divya R.; Adam, Terrence J.; Zhang, Rui

2018-01-01

The adverse events of the dietary supplements should be subject to scrutiny due to their growing clinical application and consumption among U.S. adults. An effective method for mining and grouping the adverse events of the dietary supplements is to evaluate product labeling for the rapidly increasing number of new products available in the market. In this study, the adverse events information was extracted from the product labels stored in the Dietary Supplement Label Database (DSLD) and analyzed by topic modeling techniques, specifically Latent Dirichlet Allocation (LDA). Among the 50 topics generated by LDA, eight topics were manually evaluated, with topic relatedness ranging from 58.8% to 100% on the product level, and 57.1% to 100% on the ingredient level. Five out of these eight topics were coherent groupings of the dietary supplements based on their adverse events. The results demonstrated that LDA is able to group supplements with similar adverse events based on the dietary supplement labels. Such information can be potentially used by consumers to more safely use dietary supplements. PMID:29295169

Evidence of Adverse Selection in Iranian Supplementary Health Insurance Market

PubMed Central

Mahdavi, Gh; Izadi, Z

2012-01-01

Background: Existence or non-existence of adverse selection in insurance market is one of the important cases that have always been considered by insurers. Adverse selection is one of the consequences of asymmetric information. Theory of adverse selection states that high-risk individuals demand the insurance service more than low risk individuals do. Methods: The presence of adverse selection in Iran’s supplementary health insurance market is tested in this paper. The study group consists of 420 practitioner individuals aged 20 to 59. We estimate two logistic regression models in order to determine the effect of individual’s characteristics on decision to purchase health insurance coverage and loss occurrence. Using the correlation between claim occurrence and decision to purchase health insurance, the adverse selection problem in Iranian supplementary health insurance market is examined. Results: Individuals with higher level of education and income level purchase less supplementary health insurance and make fewer claims than others make and there is positive correlation between claim occurrence and decision to purchase supplementary health insurance. Conclusion: Our findings prove the evidence of the presence of adverse selection in Iranian supplementary health insurance market. PMID:23113209

Positive childhood experiences predict less psychopathology and stress in pregnant women with childhood adversity: A pilot study of the benevolent childhood experiences (BCEs) scale.

PubMed

Narayan, Angela J; Rivera, Luisa M; Bernstein, Rosemary E; Harris, William W; Lieberman, Alicia F

2018-04-01

This pilot study examined the psychometric properties of the Benevolent Childhood Experiences (BCEs) scale, a new instrument designed to assess positive early life experiences in adults with histories of childhood maltreatment and other adversities. A counterpart to the Adverse Childhood Experiences (ACEs) questionnaire, the BCEs was developed to be multiculturally-sensitive and applicable regardless of socioeconomic position, urban-rural background, or immigration status. Higher levels of BCEs were hypothesized to predict lower levels of psychopathology and stress beyond the effects of ACES in a sample of ethnically diverse, low-income pregnant women. BCEs were also expected to show adequate internal validity across racial/ethnic groups and test-retest stability from the prenatal to the postnatal period. Participants were 101 pregnant women (M=29.10years, SD=6.56, range=18-44; 37% Latina, 22% African-American, 20% White, 21% biracial/multiracial/other; 37% foreign-born, 26% Spanish-speaking) who completed the BCEs and ACEs scales; assessments of prenatal depression and post-traumatic stress disorder (PTSD) symptoms, perceived stress, and exposure to stressful life events (SLEs) during pregnancy; and demographic information. Higher levels of BCEs predicted less PTSD symptoms and SLEs, above and beyond ACEs. The BCEs showed excellent test-retest reliability, and mean levels were comparable across racial/ethnic and Spanish-English groups of women. Person-oriented analyses also showed that higher levels of BCEs offset the effects of ACEs on prenatal stress and psychopathology. The BCEs scale indexes promising promotive factors associated with lower trauma-related symptomatology and stress exposure during pregnancy and illuminates how favorable childhood experiences may counteract long-term effects of childhood adversity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prenatal Adversities and Latino Children’s Autonomic Nervous System Reactivity Trajectories from 6 Months to 5 Years of Age

PubMed Central

Alkon, Abbey; Boyce, W. Thomas; Tran, Linh; Harley, Kim G.; Neuhaus, John; Eskenazi, Brenda

2014-01-01

The purpose of the study was to determine whether mothers’ adversities experienced during early pregnancy are associated with offspring’s autonomic nervous system (ANS) reactivity trajectories from 6 months to 5 years of age. This cohort study of primarily Latino families included maternal interviews at 13–14 weeks gestation about their experience of a range of adversities: father’s absence, general social support, poverty level, and household density. ANS measures of heart rate, respiratory sinus arrhythmia (parasympathetic nervous system) and preejection period (sympathetic nervous system) were collected during resting and challenging conditions on children at 6 months and 1, 3.5 and 5 years of age. Reactivity measures were calculated as the mean of the responses to challenging conditions minus a resting condition. Fixed effects models were conducted for the 212 children with two or more timepoints of ANS measures. Interactions between maternal prenatal adversity levels and child age at time of ANS protocol were included in the models, allowing the calculation of separate trajectories or slopes for each level of adversity. Results showed no significant relations between mothers’ prenatal socioeconomic or social support adversity and offspring’s parasympathetic nervous system trajectories, but there was a statistically significant relationship between social support adversity and offspring’s heart rate trajectories (p<.05) and a borderline significant relationship between socioeconomic adversity and offspring’s sympathetic nervous system trajectories (p = .05). Children whose mothers experienced one, not two, social support adversity had the smallest increases in heart rate reactivity compared to children whose mothers experienced no adversity. The children whose mothers experienced no social support and no socioeconomic adversity had the largest increases in heart rate and preejection period respectively from 6 months to 5 years showing the most plasticity. Mothers’ prenatal adverse experiences may program their children’s physiologic trajectory to dampen their heart rate or sympathetic responsivity to challenging conditions. PMID:24466003

Physiologically-based Pharmacokinetic(PBPK) Models Application to Screen Environmental Hazards Related to Adverse Outcome Pathways(AOPs)

EPA Science Inventory

PBPK models are useful in estimating exposure levels based on in vitro to in vivo extrapolation (IVIVE) calculations. Linkage of large sets of chemically screened vitro signature effects to in vivo adverse outcomes using IVIVE is central to the concepts of toxicology in the 21st ...

Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients.

PubMed

Shima, Hisato; Miya, Keiko; Okada, Kazuyoshi; Minakuchi, Jun; Kawashima, Shu

2018-06-08

Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients. Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients.

Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population Level Effects

EPA Science Inventory

The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitor...

Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

PubMed

El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

2011-09-01

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

Adverse effects as a consequence of being the subject of orthopaedic manual therapy training, a worldwide retrospective survey.

PubMed

Thoomes-de Graaf, M; Thoomes, E; Carlesso, L; Kerry, R; Rushton, A

2017-06-01

Physical therapists (PTs) use a range of manual therapy techniques developed to an advanced level through postgraduate orthopaedic manipulative physical therapy (OMPT) programmes. The aim of this study was to describe the adverse effects experienced by students after having techniques performed on them as part of their OMPT training. A descriptive online survey of current students and recent graduates (≤5 years)m of OMPT programmes across the 22 Member Organisations of the International Federation of Orthopaedic Manipulative Physical Therapists. The questionnaire was completed by 1640 respondents across 22 countries (1263 graduates, 377 students. Some 60% of respondents reported never having experienced adverse effects during their manual therapy training. Of the 40% who did, 66.4% reported neck pain, 50.9% headache and 32% low back pain. Most reports of neck pain started after a manipulation and/or mobilisation, of which 53.4% lasted ≤24 h, 38.1% > 24 h but <3 months and 13.7% still experienced neck pain to date. A small percentage of respondents (3.3%) reported knowing of a fellow student experiencing a major adverse effect. Mild to moderate adverse effects after practising manual therapy techniques are commonly reported, but usually resolve within 24 h. However, this survey has identified the reported occurrence of major adverse effects that warrant further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 2. Tissue biochemistry evaluation.

PubMed

Lohner, T W; Reash, R J; Williams, M

2001-11-01

Sunfish were collected from a fly ash pond-receiving stream and an Ohio River reference site to assess biochemical responses to coal ash effluent exposure. Selenium levels in sunfish from the receiving stream were higher than toxic thresholds associated with adverse population effects and reproductive impairment. Tissue biochemistry was found to be indicative of metal exposure and effect, but varied widely. Liver glycogen was positively correlated with increased liver metal levels, indicating no adverse effect upon stored carbohydrate levels. Lipid levels decreased with increasing metals, indicating possible nutritional stress. Protein levels increased with increasing metal levels, possibly due to the synthesis of proteins to sequester the metals. ATPase, dUTPase, and alkaline phosphatase activity generally decreased with exposure to ash pond metals, but remained within normal physiological ranges. Fish condition factors and liver somatic indices were correlated with liver lipid levels, dUTPase activity, and gill ATPase and alkaline phosphatase activity. Exposure to coal ash effluents produced biochemical markers of exposure that were associated with fish condition indicators; however, the indices themselves were not significantly affected by effluent exposure.

Air Pollution and Stroke

PubMed Central

Lee, Kuan Ken; Miller, Mark R.; Shah, Anoop S. V.

2018-01-01

The adverse health effects of air pollution have long been recognised; however, there is less awareness that the majority of the morbidity and mortality caused by air pollution is due to its effects on the cardiovascular system. Evidence from epidemiological studies have demonstrated a strong association between air pollution and cardiovascular diseases including stroke. Although the relative risk is small at an individual level, the ubiquitous nature of exposure to air pollution means that the absolute risk at a population level is on a par with “traditional” risk factors for cardiovascular disease. Of particular concern are findings that the strength of this association is stronger in low and middle income countries where air pollution is projected to rise as a result of rapid industrialisation. The underlying biological mechanisms through which air pollutants exert their effect on the vasculature are still an area of intense discussion. A greater understanding of the effect size and mechanisms is necessary to develop effective strategies at individual and policy levels to mitigate the adverse cardiovascular effects of air pollution. PMID:29402072

Air Pollution and Stroke.

PubMed

Lee, Kuan Ken; Miller, Mark R; Shah, Anoop S V

2018-01-01

The adverse health effects of air pollution have long been recognised; however, there is less awareness that the majority of the morbidity and mortality caused by air pollution is due to its effects on the cardiovascular system. Evidence from epidemiological studies have demonstrated a strong association between air pollution and cardiovascular diseases including stroke. Although the relative risk is small at an individual level, the ubiquitous nature of exposure to air pollution means that the absolute risk at a population level is on a par with "traditional" risk factors for cardiovascular disease. Of particular concern are findings that the strength of this association is stronger in low and middle income countries where air pollution is projected to rise as a result of rapid industrialisation. The underlying biological mechanisms through which air pollutants exert their effect on the vasculature are still an area of intense discussion. A greater understanding of the effect size and mechanisms is necessary to develop effective strategies at individual and policy levels to mitigate the adverse cardiovascular effects of air pollution.

Weight of evidence evaluation of a network of adverse ...

EPA Pesticide Factsheets

Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating many high nutrient crops, such as fruits, vegetables, and nuts. 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 target pest insects. However, mounting evidence indicates that these 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. Development of 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 norm

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

Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population Level Effects, Journal Article

EPA Science Inventory

The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitor...

A Markov chain model to evaluate the effect of CYP3A5 and ABCB1 polymorphisms on adverse events associated with tacrolimus in pediatric renal transplantation.

PubMed

Sy, Sherwin K B; Heuberger, Jules; Shilbayeh, Sireen; Conrado, Daniela J; Derendorf, Hartmut

2013-10-01

The SNP A6986G of the CYP3A5 gene (*3) results in a non-functional protein due to a splicing defect whereas the C3435T was associated with variable expression of the ABCB1 gene, due to protein instability. Part of the large interindividual variability in tacrolimus efficacy and toxicity can be accounted for by these genetic factors. Seventy-two individuals were examined for A6986G and C3435T polymorphism using a PCR-RFLP-based technique to estimate genotype and allele frequencies in the Jordanian population. The association of age, hematocrit, platelet count, CYP3A5, and ABCB1 polymorphisms with tacrolimus dose- and body-weight-normalized levels in the subset of 38 pediatric renal transplant patients was evaluated. A Markov model was used to evaluate the time-dependent probability of an adverse event occurrence by CYP3A5 phenotypes and ABCB1 genotypes. The time-dependent probability of adverse event was about double in CYP3A5 non-expressors compared to the expressors for the first 12 months of therapy. The CYP3A5 non-expressors had higher corresponding normalized tacrolimus levels compared to the expressors in the first 3 months. The correlation trend between probability of adverse events and normalized tacrolimus concentrations for the two CYP3A5 phenotypes persisted for the first 9 months of therapy. The differences among ABCB1 genotypes in terms of adverse events and normalized tacrolimus levels were only observed in the first 3 months of therapy. The information on CYP3A5 genotypes and tacrolimus dose requirement is important in designing effective programs toward management of tacrolimus side effects particularly for the initial dose when tacrolimus blood levels are not available for therapeutic drug monitoring.

Effects of chocolate-based products intake on blood glucose, insulin and ghrelin levels and on satiety in young people: a cross-over experimental study.

PubMed

Zhang, Cai-Xia; Long, Wei-Qing; Ye, Yan-Bin; Lu, Min-Shan; Zhang, Nai-Qi; Xu, Ming; Huang, Jing; Su, Yi-Xiang

2018-02-19

This cross-over experimental study aimed to examine the effects of filled chocolate consumption on blood glucose, insulin and ghrelin levels in 20 volunteers. After a one-week run-in period, study participants consumed two chocolate-based products, the tested biscuit or water for 21 days as a morning snack. After a two-week wash-out period, participants consumed another tested food for another 21 days. Each participant consumed all four test foods within an 18-week period. The participants' blood insulin increased slowly after two chocolate-based products intakes on the first day and satiety levels after eating chocolate-based products and the tested biscuit were the same. Chocolate consumption for three weeks had no adverse effects on blood glucose, insulin or ghrelin levels. In conclusion, compared to eating the tested biscuit, 21-day consumption of the tested chocolate-based products had no adverse effects on the blood glucose, insulin and ghrelin levels. This trial is registered with chictr.org.cn: ChiCTR-IOR-16009525.

Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

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

Chen Yu; Parvez, Faruque; Gamble, Mary

2009-09-01

The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 {mu}g/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 {mu}g/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 {mu}g/L, mean 99 {mu}g/L) of arsenic exposure. Findings to date suggestmore » adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.« less

Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events.

PubMed

Haas, David W; Bradford, Yuki; Verma, Anurag; Verma, Shefali S; Eron, Joseph J; Gulick, Roy M; Riddler, Sharon A; Sax, Paul E; Daar, Eric S; Morse, Gene D; Acosta, Edward P; Ritchie, Marylyn D

2018-05-29

We characterized associations between central nervous system (CNS) adverse events and brain neurotransmitter transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10). Efavirenz-related CNS adverse events were not associated with predicted neurotransmitter transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain neurotransmitter transporter/receptor genomics.

Nanoparticles and spermatogenesis: how do nanoparticles affect spermatogenesis and penetrate the blood-testis barrier.

PubMed

Lan, Zhou; Yang, Wan-Xi

2012-04-01

Due to the widespread use of nanomaterials in medical, industrial and military applications, the question as to whether nanoparticles (NPs) cause harmful disturbances in human health, especially on the reproductive system, remains a matter of concern. In this review, we focus mainly on the in vivo and in vitro effects of NPs on spermatogenesis at the clinical, cellular and molecular levels. In general, most NPs display adverse effects on spermatogenesis at these various levels; but, some NPs show no adverse effects. However, the mechanism underlying NP disruption of spermatogenesis and penetration of the blood-testis barrier remains unclear. In this review, we raise many hypotheses for experimental testing in order to elucidate the mechanism.

Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. I. Subacute exposures.

PubMed

Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

2015-02-01

The inhalation toxicity of submarine contaminants is of concern to ensure the health of men and women aboard submarines during operational deployments. Due to a lack of adequate prior studies, potential general, neurobehavioral, reproductive and developmental toxicity was evaluated in male and female rats exposed to mixtures of three critical submarine atmospheric components: carbon monoxide (CO) and carbon dioxide (CO2; levels elevated above ambient), and oxygen (O2; levels decreased below ambient). In a 14-day, 23 h/day, whole-body inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO2 and 20.6% O2), low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO2 and 15.0% O2), no adverse effects on survival, body weight or histopathology were observed. Reproductive, developmental and neurobehavioral performance were evaluated after a 28-day exposure in similar atmospheres. No adverse effects on estrus phase, mating, gestation or parturition were observed. No developmental or functional deficits were observed in either exposed parents or offspring related to motor activity, exploratory behavior or higher-level cognitive functions (learning and memory). Only minimal effects were discovered in parent-offspring emotionality tests. While statistically significant increases in hematological parameters were observed in the offspring of exposed parents compared to controls, these parameters remained within normal clinical ranges for blood cells and components and were not considered adverse. In summary, subacute exposures to elevated concentrations of the submarine atmosphere gases did not affect the ability of rats to reproduce and did not appear to have any significant adverse health effects.

Is Prenatal Alcohol Exposure Related to Inattention and Hyperactivity Symptoms in Children? Disentangling the Effects of Social Adversity

ERIC Educational Resources Information Center

Rodriguez, A.; Olsen, J.; Kotimaa, A. J.; Kaakinen, M.; Moilanen, I.; Henriksen, T. B.; Linnet, K. M.; Miettunen, J.; Obel, C.; Taanila, A.; Ebeling, H.; Jarvelin, M. R.

2009-01-01

Background: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting…

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

Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population Level Effects: Report of Pellston Workgroup 3

EPA Science Inventory

The continuing persistence and genetic diversity of populations is a key concern for environmental regulations. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-speci...

Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP).

PubMed

Besi, E; Boniface, D R; Cregg, R; Zakrzewska, J M

2015-01-01

Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs (AEDs), in particular carbamazepine (CBZ) and oxcarbazepine (OXC) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile (AEP) and provide clinicians with guidance as to when to change management. The study was conducted as a clinical prospective observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years. At each consultation they completed the AEP questionnaire which provides scores of 19-76 with toxic levels being considered as scores >45. The most common significant side effects were: tiredness 31.3 %, sleepiness 18.2 %, memory problems 22.7 %, disturbed sleep 14.1 %, difficulty concentrating and unsteadiness 11.6 %. Females reported significantly more side effects than males. Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and1800mg of OXC and 1200 mg of CBZ for males. CBZ and OXC are associated with cognitive impairment. Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects. Potentially, females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages. Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management.

Comfort eating, psychological stress, and depressive symptoms in young adult women.

PubMed

Finch, Laura E; Tomiyama, A Janet

2015-12-01

Little is known about whether comfort eating actually functions to reduce psychological stress. In addition, the effectiveness of comfort eating may be particularly relevant in the context of depression, but no study has tested whether comfort eating processes might depend on severity of depressive symptomology. This study tested 1) whether greater comfort eating statistically buffers the relationship between adverse life events and perceived psychological stress at age 18-19, and 2) whether potential stress-buffering effects may differ by level of depressive symptoms. These relationships were examined in the NHLBI Growth and Health Study, comprising 2379 young adult women. Participants self-reported experiences with adverse life events, their perceived psychological stress, and whether they tended to eat more while experiencing certain negative emotions. As hypothesized, the relationship between adverse life events and perceived stress depended on comfort eating status (p = .033). The effect of adverse events on perceived stress was attenuated among comfort eaters compared to non-comfort eaters (p = .004), but this buffering effect was not shown in participants with an elevated level of depressive symptoms. In conclusion, among young adult women without high depressive symptoms, comfort eaters may experience reduced perceived stress compared to those who do not engage in this behavior. Intervention researchers should also consider the possible benefits of comfort eating. Copyright © 2015 Elsevier Ltd. All rights reserved.

Air pollution in India and related adverse respiratory health effects: past, present, and future directions.

PubMed

Khilnani, Gopi C; Tiwari, Pawan

2018-03-01

The review describes current status of air pollution in India, summarizes recent research on adverse health effects of ambient and household air pollution, and outlines the ongoing efforts and future actions required to improve air quality and reduce morbidity and mortality because of air pollution in India. Global burden of disease data analysis reveals more than one million premature deaths attributable to ambient air pollution in 2015 in India. More than one million additional deaths can be attributed to household air pollution. Particulate matter with diameter 2.5 μm or less has been causatively linked with most premature deaths. Acute respiratory tract infections, asthma, chronic obstructive pulmonary disease, exacerbations of preexisting obstructive airway disease and lung cancer are proven adverse respiratory effects of air pollution. Targeting air quality standards laid by WHO can significantly reduce morbidity and mortality because of air pollution in India. India is currently exposed to high levels of ambient and household air pollutants. Respiratory adverse effects of air pollution are significant contributors to morbidity and premature mortality in India. Substantial efforts are being made at legislative, administrative, and community levels to improve air quality. However, much more needs to be done to change the 'status quo' and attain the target air quality standards. VIDEO ABSTRACT: http://links.lww.com/COPM/A24.

Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications.

PubMed

Sadeu, J C; Hughes, Claude L; Agarwal, Sanjay; Foster, Warren G

2010-08-01

Reproductive function and fertility are thought to be compromised by behaviors such as cigarette smoking, substance abuse, and alcohol consumption; however, the strength of these associations are uncertain. Furthermore, the reproductive system is thought to be under attack from exposure to environmental contaminants, particularly those chemicals shown to affect endocrine homeostasis. The relationship between exposure to environmental contaminants and adverse effects on human reproductive health are frequently debated in the scientific literature and these controversies have spread into the lay press drawing increased public and regulatory attention. Therefore, the objective of the present review was to critically evaluate the literature concerning the relationship between lifestyle exposures and adverse effects on fertility as well as examining the evidence for a role of environmental contaminants in the purported decline of semen quality and the pathophysiology of subfertility, polycystic ovarian syndrome, and endometriosis. The authors conclude that whereas cigarette smoking is strongly associated with adverse reproductive outcomes, high-level exposures to other lifestyle factors are only weakly linked with negative fertility impacts. Finally, there is no compelling evidence that environmental contaminants, at concentrations representative of the levels measured in contemporary biomonitoring studies, have any effect, positive or negative, on reproductive health in the general population. Further research using prospective study designs with robust sample sizes are needed to evaluate testable hypotheses that address the relationship between exposure and adverse reproductive health effects.

Managing statin-induced muscle toxicity in a lipid clinic.

PubMed

Blaier, O; Lishner, M; Elis, A

2011-06-01

Muscle toxicity is the most significant adverse effect related to statins. The aim of the study was to analyse the clinical course and achievement of LDL-C target levels in patients with statin-induced muscle toxicity. All patients who were referred to the lipid clinic because of statin-induced muscle toxicity, or developed it during follow-up, or did not reach LDL-C target levels because of its previous occurrence, and attended the clinic for at least three follow-up visits, were eligible. Files were reviewed for demographic and clinical parameters, coronary heart disease risk level, the severity of muscle injury, the type of statin and dose that caused the adverse effects, the clinical approach and outcome, and whether the LDL-C target level was achieved. The study group consisted of 54 patients. Twenty-three (43%) patients complained of myalgia, 23 (43%) had asymptomatic serum creatine kinase (CK) level elevation, five (9%) had myopathy and three (5%) had rhabdomyolysis. Fifty of the patients (93%) continued statin therapy and 43 (80%) achieved the LDL-C target level. We show that for the majority of patients with statin-induced muscle toxicity, statin therapy can be safely and effectively continued. In cases of asymptomatic CK levels <3-5 upper limit of normal (ULN), statin treatment should not be interrupted. When CK levels >3-5 ULN or when various symptomatic muscle adverse reactions are present, statins rechallenge, after a recovery period, should be individualized either by a low dose of a potent statin or by a less potent statin. An additional lipid medication is advised if the target levels are not achieved. © 2011 Blackwell Publishing Ltd.

Mold exposure and health effects following hurricanes Katrina and Rita.

PubMed

Barbeau, Deborah N; Grimsley, L Faye; White, LuAnn E; El-Dahr, Jane M; Lichtveld, Maureen

2010-01-01

The extensive flooding in the aftermath of Hurricanes Katrina and Rita created conditions ideal for indoor mold growth, raising concerns about the possible adverse health effects associated with indoor mold exposure. Studies evaluating the levels of indoor and outdoor molds in the months following the hurricanes found high levels of mold growth. Homes with greater flood damage, especially those with >3 feet of indoor flooding, demonstrated higher levels of mold growth compared with homes with little or no flooding. Water intrusion due to roof damage was also associated with mold growth. However, no increase in the occurrence of adverse health outcomes has been observed in published reports to date. This article considers reasons why studies of mold exposure after the hurricane do not show a greater health impact.

75 FR 19272 - Thifensulfuron methyl; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... background exposure level). A short and intermediate-term adverse effect was identified; however... of small renal papillae (only at the highest dose level). Thifensulfuron methyl is classified as... only at the mid-level dose of 177 mg/kg. The lack of response at the high-level dose, the occurrence in...

Serum retinol, alpha-tocopherol, and beta-carotene levels are not altered by excess ingestion of diacylglycerol-containing plant sterol esters.

PubMed

Saito, Shinichiro; Tomonobu, Kazuichi; Kudo, Naoto; Shiiba, Daisuke; Hase, Tadashi; Tokimitsu, Ichiro

2006-01-01

Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, beta-carotene, and alpha-tocopherol levels using a threefold excess of the effective dose obtained in our previous study. A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control. There were no subjective adverse effects or changes in serum retinol, alpha-tocopherol, and beta-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values. Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise. Copyright 2006 S. Karger AG, Basel.

Childhood abuse affects emotional closeness with family in mid- and later life.

PubMed

Savla, J Tina; Roberto, Karen A; Jaramillo-Sierra, Ana L; Gambrel, Laura Eubanks; Karimi, Hassan; Butner, L Michelle

2013-06-01

Knowledge about the effects of early life adversity on kin relationships in later years is sparse. The purpose of this study was to examine if childhood abuse and adversity negatively influences emotional closeness with family in mid- and later life. A second goal was to determine the role of psychosocial resources and personality traits in buffering the effects of early adversities. Gender and cohort differences were explored to see if men were differentially affected than women and whether middle-aged adults (35-49 years old) were differentially affected than older adults (50-74 years old) by the effects of childhood abuse and adversity. Using retrospective accounts of early family abuse and adversities of 1,266 middle aged adults and 1,219 older adults from a large population-based survey, the National Survey of Midlife Development in United States (MIDUS), separate multiple regression analyses were conducted for the two cohorts to examine the effects of childhood emotional and physical abuse and family adversities on perceived emotional closeness with family. Interaction effects between childhood abuse and adversity (e.g., being expelled from school, death of sibling, parental divorce, losing a home to a natural disaster) with psychosocial resources (perceived control and self acceptance), personality characteristics (extraversion and neuroticism), and gender were examined. Results of OLS regressions suggest emotional and physical abuse predicted family closeness in middle-aged adults. Conversely, only emotional abuse predicted family closeness in older adults. Moderation models revealed that high levels of self acceptance were associated with better maintenance of emotional closeness among middle-aged adults who were emotionally and physically abused as children. Older adults with lower extraversion who experienced emotional abuse or reported greater number of adversities in childhood were found to be at higher risk for lower emotional closeness with family. Early life adversities were more detrimental for women. Findings suggest that the aftermath of childhood abuse does not dissipate with time, but continues to influence family relationships in mid- and later life. Identifying the links between childhood adversities and adult relationships can help identify strategic points for intervention to reduce the long-term effects of accumulated adverse experiences over the life course. Published by Elsevier Ltd.

Toxicological relevance of pharmaceuticals in drinking water.

PubMed

Bruce, Gretchen M; Pleus, Richard C; Snyder, Shane A

2010-07-15

Interest in the public health significance of trace levels of pharmaceuticals in potable water is increasing, particularly with regard to the effects of long-term, low-dose exposures. To assess health risks and establish target concentrations for water treatment, human health risk-based screening levels for 15 pharmaceutically active ingredients and four metabolites were compared to concentrations detected at 19 drinking water treatment plants across the United States. Compounds were selected based on rate of use, likelihood of occurrence, and potential for toxicity. Screening levels were established based on animal toxicity data and adverse effects at therapeutic doses, focusing largely on reproductive and developmental toxicity and carcinogenicity. Calculated drinking water equivalent levels (DWELs) ranged from 0.49 microg/L (risperidone) to 20,000 microg/L (naproxen). None of the 10 detected compounds exceeded their DWEL. Ratios of DWELs to maximum detected concentrations ranged from 110 (phenytoin) to 6,000,000 (sulfamethoxazole). Based on this evaluation, adverse health effects from targeted pharmaceuticals occurring in U.S. drinking water are not expected.

Application of ToxCast to evaluate potential biological effects ...

EPA Pesticide Factsheets

With the development of “high throughput” in-vitro biological assays, screening-level information on potential adverse biological effects is available for a rapidly increasing number of chemicals. The U.S. EPA ToxCast program has now evaluated several thousand chemicals with more than 800 assays. The original intent of this data was to evaluate potential for human health effects, but it is now being extended to environmental health evaluations. The R package ToxEval was developed as a screening tool to use ToxCast results for evaluation of potential adverse biological effects from trace organic chemicals in water samples. Using ToxEval, trace organic chemical data from water samples and passive samplers collected at 57 Great Lakes tributaries from 2010-2013 were examined to determine the tributaries with the greatest potential for adverse biological effects with prioritization of the most influential contaminants. Results are being used as part of the Great Lakes Restoration Initiative to focus current and future investigations that will help understand likely adverse outcome pathways in biological organisms, and to formulate possible remediation strategies. not applicable

BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study.

PubMed

Buchmann, Arlette F; Hellweg, Rainer; Rietschel, Marcella; Treutlein, Jens; Witt, Stephanie H; Zimmermann, Ulrich S; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Laucht, Manfred; Deuschle, Michael

2013-08-01

Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype. Copyright © 2013. Published by Elsevier B.V.

Acoustic Aspects of Active-Twist Rotor Control

NASA Technical Reports Server (NTRS)

Booth, Earl R., Jr.; Wilbur, Matthew L.

2002-01-01

The use of an Active Twist Rotor system to provide both vibration reduction and performance enhancement has been explored in recent analytical and experimental studies. Effects of active-twist control on rotor noise, however, had not been determined. During a recent wind tunnel test of an active-twist rotor system, a set of acoustic measurements were obtained to assess the effects of active-twist control on noise produced by the rotor, especially blade-vortex interaction (BVI) noise. It was found that for rotor operating conditions where BVI noise is dominant, active-twist control provided a reduction in BVI noise level. This BVI noise reduction was almost, but not quite, as large as that obtained in a similar test using HHC. However, vibration levels were usually adversely affected at operating conditions favoring minimum BVI noise. Conversely, operating conditions favoring minimum vibration levels affected BVI noise levels, but not always adversely.

Childhood adversities and clinical symptomatology in first-episode psychosis.

PubMed

Lindgren, Maija; Mäntylä, Teemu; Rikandi, Eva; Torniainen-Holm, Minna; Morales-Muñoz, Isabel; Kieseppä, Tuula; Mantere, Outi; Suvisaari, Jaana

2017-12-01

In addition to severe traumatic experiences, milder, more common childhood adversities reflecting psychosocial burden may also be common in people with psychotic disorders and have an effect on symptomatology and functioning. We explored eleven negative childhood experiences and their influence on clinical symptoms among young adults with first-episode psychosis (FEP, n = 75) and matched population controls (n = 51). Individuals with FEP reported more adversities than controls. Specifically serious conflicts within the family, bullying at school, maternal mental health problems, and one's own and parents' serious illness during childhood were experienced by the patients more often than by controls. In the FEP group, the severity of adversity was associated with increased anxiety, manic, and obsessive-compulsive symptoms, but not with the severity of positive psychotic symptoms. Adversity produced a more pronounced effect on symptoms in male patients than in female patients. To conclude, in line with earlier studies of more chronic psychosis, a majority of the participants with FEP reported exposure to childhood adversities, with the FEP group reporting more adversities than controls. High levels of mood and anxiety symptoms in patients with FEP may be related to cumulative exposure to childhood adversities. This should be taken into account in the treatment for FEP. Copyright © 2017 Elsevier B.V. All rights reserved.

Biological Relevance of Key Events (KE) in utero in The Androgen Adverse Outcome Pathway Network (AOPn) to Adverse Effects in F1 Male Rats

EPA Science Inventory

We are conducting studies to evaluate the biological relevance of changes in KEs and molecular initiating events (MIE) in AOPs to determine if these can accurately predict of the dose levels of chemicals that disrupt the androgen signaling pathway in utero. Herein, we focus on ch...

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem.

PubMed

Kabiru, Caroline W; Elung'ata, Patricia; Mojola, Sanyu A; Beguy, Donatien

2014-01-01

Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? We used cross-sectional data from 3,064 males and females aged 12-19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries.

Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

PubMed Central

Mossa, Abdel-Tawab H.; Ibrahim, Faten M.; Mohafrash, Samia M. M.; Abou Baker, Doha H.; El Gengaihi, Souad

2015-01-01

The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1 body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1 body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity. PMID:26265923

Multigenerational Exposure of the Estuarine Sheepshead Minnow (Cyprinodon variegatus) to 17β-estradiol. II. Population-Level Effects Through Two Life Cycles

EPA Science Inventory

The evaluation of multi-generation, population-level impacts is particularly important in the risk assessment of endocrine disrupting compounds (EDCs) because adverse effects may not be evident during the first generation of exposure. Population models were developed for the shee...

Ocean acidification effects on calcification in pCO2 acclimated Caribbean scleractinian coral

EPA Science Inventory

Ocean acidification (OA) is projected to increase the acidity of coral reef habitats 2-3 times that of present day pCO2 levels. Many studies have shown the adverse effects on scleractinian calcification when exposed to elevated pCO2 levels, however, in these studies, corals have ...

40 CFR 159.184 - Toxic or adverse effect incident reports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... pesticide was detected at levels greater than the maximum contaminant level (MCL) or health advisory level...) PESTICIDE PROGRAMS STATEMENTS OF POLICIES AND INTERPRETATIONS Reporting Requirements for Risk/Benefit... affecting humans or other non-target organisms must be submitted if the following three conditions are met...

40 CFR 159.184 - Toxic or adverse effect incident reports.

Code of Federal Regulations, 2014 CFR

2014-07-01

... pesticide was detected at levels greater than the maximum contaminant level (MCL) or health advisory level...) PESTICIDE PROGRAMS STATEMENTS OF POLICIES AND INTERPRETATIONS Reporting Requirements for Risk/Benefit... affecting humans or other non-target organisms must be submitted if the following three conditions are met...

40 CFR 159.184 - Toxic or adverse effect incident reports.

Code of Federal Regulations, 2013 CFR

2013-07-01

... pesticide was detected at levels greater than the maximum contaminant level (MCL) or health advisory level...) PESTICIDE PROGRAMS STATEMENTS OF POLICIES AND INTERPRETATIONS Reporting Requirements for Risk/Benefit... affecting humans or other non-target organisms must be submitted if the following three conditions are met...

40 CFR 159.184 - Toxic or adverse effect incident reports.

Code of Federal Regulations, 2011 CFR

2011-07-01

... pesticide was detected at levels greater than the maximum contaminant level (MCL) or health advisory level...) PESTICIDE PROGRAMS STATEMENTS OF POLICIES AND INTERPRETATIONS Reporting Requirements for Risk/Benefit... affecting humans or other non-target organisms must be submitted if the following three conditions are met...

40 CFR 159.184 - Toxic or adverse effect incident reports.

Code of Federal Regulations, 2012 CFR

2012-07-01

... pesticide was detected at levels greater than the maximum contaminant level (MCL) or health advisory level...) PESTICIDE PROGRAMS STATEMENTS OF POLICIES AND INTERPRETATIONS Reporting Requirements for Risk/Benefit... affecting humans or other non-target organisms must be submitted if the following three conditions are met...

Relationships of maternal and fetal weight changes in developmental toxicology bioassays

EPA Science Inventory

Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines require the inclusion of a dose level(s) that induces “overt maternal toxicity”. The common occurrence of dose levels at which ...

Manganese in Madison's drinking water.

PubMed

Schlenker, Thomas; Hausbeck, John; Sorsa, Kirsti

2008-12-01

Public concern over events of manganese-discolored drinking water and the potential for adverse health effects from exposure to excess manganese reached a high level in 2005. In response, Public Health Madison Dane County, together with the Madison Water Utility, conceived and implemented a public health/water utility strategy to quantify the extent of the manganese problem, determine the potential for adverse human health effects, and communicate these findings to the community. This strategy included five basic parts: taking an inventory of wells and their manganese levels, correlating manganese concentration with turbidity, determining the prevalence and distribution of excess manganese in Madison households, reviewing the available scientific literature, and effectively communicating our findings to the community. The year-long public health/water utility strategy successfully resolved the crisis of confidence in the safety of Madison's drinking water.

Maternal programming of defensive responses through sustained effects on gene expression.

PubMed

Zhang, Tie-Yuan; Bagot, Rose; Parent, Carine; Nesbitt, Cathy; Bredy, Timothy W; Caldji, Christian; Fish, Eric; Anisman, Hymie; Szyf, Moshe; Meaney, Michael J

2006-07-01

There are profound maternal effects on individual differences in defensive responses and reproductive strategies in species ranging literally from plants to insects to birds. Maternal effects commonly reflect the quality of the environment and are most likely mediated by the quality of the maternal provision (egg, propagule, etc.), which in turn determines growth rates and adult phenotype. In this paper we review data from the rat that suggest comparable forms of maternal effects on defensive responses stress, which are mediated by the effects of variations in maternal behavior on gene expression. Under conditions of environmental adversity maternal effects enhance the capacity for defensive responses in the offspring. In mammals, these effects appear to 'program' emotional, cognitive and endocrine systems towards increased sensitivity to adversity. In environments with an increased level of adversity, such effects can be considered adaptive, enhancing the probability of offspring survival to sexual maturity; the cost is that of an increased risk for multiple forms of pathology in later life.

Effects of air ions on the neonatal growth of laboratory rats

NASA Astrophysics Data System (ADS)

Hinsull, S. M.; Bellamy, D.; Head, E. L.

1981-12-01

The effect of continuous positive and negative ionization on the growth of rats during the pre and post natal period, up to 10 weeks of age was investigated. It was found that continuous exposure to 1.0×104 pos. ions/ml had no detrimental effect on the animals at any stage of their development. In contrast, exposure to 1.0×104 neg. ions/ml, during gestation and the early post natal period, resulted in some adverse effects on growth and development. However, when exposure to this level of negative ions began at the time of weaning, no adverse effects were observed.

Adverse outcome pathways: a concise introduction for toxicologists

PubMed Central

Vergauwen, Lucia; Hengstler, Jan G.; Angrish, Michelle; Whelan, Maurice

2018-01-01

Adverse outcome pathways are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use adverse outcome pathways, have been published in the last few years. The present paper provides a synopsis of the main principles related to the adverse outcome pathway framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology. PMID:28660287

Classroom-level adversity: Associations with children's internalizing and externalizing behaviors across elementary school.

PubMed

Abry, Tashia; Bryce, Crystal I; Swanson, Jodi; Bradley, Robert H; Fabes, Richard A; Corwyn, Robert F

2017-03-01

Concerns regarding the social-behavioral maladjustment of U.S. youth have spurred efforts among educators and policymakers to identify and remedy educational contexts that exacerbate children's anxiety, depression, aggression, and misconduct. However, investigations of the influence of collective classroom student characteristics on individuals' social-behavioral functioning are few. The present study examined concurrent and longitudinal relations between adversity factors facing the collective classroom student group and levels of children's internalizing and externalizing behaviors across the elementary school years, and whether the pattern of relations differed for girls and boys. First-, third-, and fifth-grade teachers reported on the extent to which adversity-related factors (e.g., home/family life, academic readiness, social readiness, English proficiency, tardiness/absenteeism, student mobility, health) presented a challenge in their classrooms (i.e., classroom-level adversity [CLA]). Mothers reported on their child's internalizing and externalizing behavior at each grade. Autoregressive, lagged panel models controlled for prior levels of internalizing and externalizing behavior, mothers' education, family income-to-needs, and class size. For all children at each grade, CLA was concurrently and positively associated with externalizing behavior. For first-grade girls, but not boys, CLA was also concurrently and positively associated with internalizing behavior. Indirect effects suggested CLA influenced later internalizing and externalizing behavior through its influence on maladjustment in a given year. Discussion highlights possible methods of intervention to reduce CLA or the negative consequences associated with being in a higher-adversity classroom. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Environmental adversity and children's early trajectories of problem behavior: The role of harsh parental discipline.

PubMed

Flouri, Eirini; Midouhas, Emily

2017-03-01

This study was performed to examine the role of harsh parental discipline in mediating and moderating the effects of environmental adversity (family socioeconomic disadvantage and adverse life events) on emotional and behavioral problems across early-to-middle childhood. The sample included 16,916 children (48% female; 24% non-White) from the U.K.'s Millennium Cohort Study. We analyzed trajectories of conduct, hyperactivity, and emotional problems, measured at ages 3, 5, and 7 years, using growth curve models. Harsh parental discipline was measured at these ages with parent-reported items on the frequency of using the physical and verbal discipline tactics of smacking, shouting at, and "telling off" the child. As expected, family socioeconomic disadvantage and adverse life events were significantly associated with emotional and behavioral problems. Harsh parental discipline was related to children's trajectories of problems, and it moderated, but did not explain, the effect of environmental risk on these trajectories. High-risk children experiencing harsh parental discipline had the highest levels of conduct problems and hyperactivity across the study period. In addition, harsh parental discipline predicted an increase in emotional symptoms over time in high-risk children, unseen in their counterparts experiencing low levels of harsh parental discipline. However, children in low-risk families were also negatively affected by harsh parental discipline concurrently and over time. In conclusion, harsh parental discipline predicted emotional and behavioral problems in high- and low-risk children and moderated the effects of family poverty and adversity on these problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Audible and infrasonic noise levels in the cabins of modern agricultural tractors--does the risk of adverse, exposure-dependent effects still exist?

PubMed

Bilski, Bartosz

2013-06-01

The agricultural tractor is one of the most commonly used vehicles on farms and one of the most prominent sources of noise. This article presents an exemplary assessment of the audible and infrasonic noise levels in the cabins of selected modern wheeled agricultural tractors. Operator-perceived audible and infrasonic noise levels in the cabins were examined for 20 types of modern tractors during typical conditions of work. The tractors had been in use for no longer than 3 years, with rated power between 96 kW and 227 kW, designed and produced by world-renowned companies. Noise level measurements were performed in accordance with PN-EN ISO 9612:2011 (ISO 9612:2009). Audible noise levels (A-weighted) ranged from 62.1 to 87.4 dB-A (average: 68.2 to 83.8 dB-A) for different work tasks. The factors influencing noise levels include performed tasks, soil, weather conditions and the skills of individual drivers. In spectrum analysis, the highest noise levels occurred at frequencies 250 Hz, 1 and 2 kHz. Infrasound noise levels (G-weighted) ranged from 87.3 to 111.3 dB-G. The driver-experienced exposure to infrasound was found to increase significantly when the vehicle was in motion. Average audible noise levels have no potential to adversely affect the hearing organ during tasks performed inside the closed cabins of the analysed modern agricultural tractors. Due to the relatively low audible noise levels inside the cabins of modern agricultural tractors, non-auditory effects are the only adverse symptoms that can develop. Modern agricultural tractors emit considerable infrasonic noise levels. All tractors introduced into the market should be subjected to tests with regard to infrasonic noise levels.

Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin.

PubMed

Kawamori, Ryuzo; Kaku, Kohei; Hanafusa, Toshiaki; Ioriya, Katsuhisa; Kageyama, Shigeru; Hotta, Nigishi

2016-03-01

The aim of the present study was to evaluate the long-term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase-4 inhibitor, sitagliptin, in addition to diet and exercise therapies. This was a multicenter, uncontrolled, dose-titration study with a treatment period of 52 weeks. The primary end-point was the change in glycated hemoglobin levels from baseline. The glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were -0.44 ± 0.28% and -0.50 ± 0.82%, respectively. The glycated hemoglobin-lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of 'major hypoglycemia'. Combination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.

Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer.

PubMed

Jiang, W W; Wang, Q H; Peng, P; Liao, Y J; Duan, H X; Xu, M; Li, Y; Zhang, P B

2015-12-09

We explored the effects of flurbiprofen axetil on interleukin (IL)-2 and IL-6 levels in postoperative patients with colorectal cancer. A total of 120 patients (American Society of Anesthesiologists I and II) scheduled to undergo colorectal cancer surgery were randomly divided into 3 groups (N = 40 in each group): flurbiprofen axetil group (group F), morphine group (group M), and tramadol group (group T). Group M received 0.1 mg/kg morphine, group T received 1.5 mg/kg tramadol, and group F received 1.5 mg/kg flurbiprofen axetil. Patients in the 3 groups were administered treatments through intravenous injection 10 min before surgery. Serum IL-2 and IL-6 levels were detected. Postoperative adverse reactions were recorded, such as nausea, vomiting, and pruritus. The serum IL-6 level of the 3 groups increased 3 h after surgery. Compared with group M, IL-6 level was higher in group T and group F at 1 day after the surgery, and the differences between group M and the other groups were significant (P < 0.05). Moreover, the incidence of adverse reactions was significantly different among 3 groups (P < 0.05). Flurbiprofen axetil promoted the secretion of IL-2 and inhibited IL-6; additionally, flurbiprofen axetil may have a lower incidence of adverse reactions compared to other treatments.

Air pollution and respiratory viral infection

EPA Science Inventory

Despite current regulations, which limit the levels of certain air pollutants, there are still a number of adverse health effects that result from exposure to these agents. Numerous epidemiological studies have noted an association between the levels of air pollution and hospital...

Effect of varying durations of pyramid exposure - an indication towards a possibility of overexposure.

PubMed

Bhat, Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

2009-10-01

Miniature replicas modeled after the Great Pyramid of Giza are believed to concentrate geoelectromagnetic energy within their cavities and hence act as antistressors in humans and animals. Although there are not many reports of adverse effects of 'overexposure' in the pyramid, subjects have claimed to feel uneasy after certain duration of staying in the pyramid. The present study was aimed to analyze the effects of prolonged pyramid exposure on plasma cortisol level, markers of oxidative damage and antioxidant defense in erythrocytes of adult female Wistar rats. Rats were divided into three groups, normal controls (NC, n=6) that were maintained under standard laboratory conditions in their home cages, pyramid exposed group-2 (PE-2, n=6) & pyramid exposed group-4 (PE-4, n=6) where the rats were housed under the pyramid for 6 hours/day for 2 weeks and 4 weeks respectively. Plasma cortisol and erythrocyte TBARS levels were significantly lower in both PE-2 and PE-4 rats and erythrocyte GSH levels and GSH-Px activity were significantly higher in them as compared to the NC rats. There was no significant difference in the results for these parameters between the PE-2 and PE-4 rats except for erythrocyte GSH-Px activity which was significantly more in the PE-2 rats than in the PE-4 rats. Although these results don't confirm any adverse effects of prolonged exposure in pyramids, they indicate a possibility of such adverse effects.

The long arm of community: the influence of childhood community contexts across the early life course.

PubMed

Wickrama, K A S; Noh, Samuel

2010-08-01

This study examines the longitudinal effects of childhood community contexts on young adult outcomes. The study uses a sample of 14,000 adolescents (52% female) derived from the 1990 US Census and the National Longitudinal Study of Adolescent Health (Addhealth). The study examines whether community and family environments exert separate and/or joint long-term influences on young adult achievement and depression. We found both direct and indirect long-term influences of childhood community adversity on young adult educational attainment. The indirect influences of childhood community adversity operated through family and individual-level factors. The long-term influence of childhood community adversity on young adult depression was only indirect. Overall, community influences on young adult achievement outcomes were mediated by family context and by the adolescents' adjustments and transitions, including adolescent depression, school adjustment, and disruptive transitional events. The moderating effect of childhood community adversity suggests that the protective effects of family resources on young adult outcomes dissipate significantly in extremely adverse neighborhoods. The findings demonstrate the importance of integrating multiple theoretical perspectives for longitudinal research to capture pathways of community influence on adolescent developmental and young adulthood outcomes.

Effects of excess biotin administration on the growth and urinary excretion of water-soluble vitamins in young rats.

PubMed

Sawamura, Hiromi; Fukuwatari, Tsutomu; Shibata, Katsumi

2007-12-01

To determine the effects of excess biotin administration on growth and water-soluble vitamin metabolism, weaning rats were fed on a 20% casein diet containing 0.00002% biotin, or same diet with 0.04, 0.08, 0.10, 0.20, 0.50, 0.80 or 1.0% added biotin for 28 days. More than 0.08% biotin administration decreased the food intake and body weight gain compared with the levels in control rats. An accumulation of biotin in such tissues as the liver, brain and kidney increased in a dose-dependent manner, and the both bound and free biotin contents in the liver also increased in a dose-dependent manner. An excess administration of biotin did not affect the urinary excretion of other water-soluble vitamins, suggesting no effect on the metabolism of other water-soluble vitamins. The results of the food intake and body weight gain indicated that the lowest observed adverse effect level for young rats was 79.2 mg/kg body weight/day, while the no observed adverse effect level was 38.4 mg/kg/day. These results suggested immediately setting a tolerable upper intake level for biotin.

Adverse effects of methylmercury (MeHg) on life parameters, antioxidant systems, and MAPK signaling pathways in the rotifer Brachionus koreanus and the copepod Paracyclopina nana.

PubMed

Lee, Young Hwan; Kim, Duck-Hyun; Kang, Hye-Min; Wang, Minghua; Jeong, Chang-Bum; Lee, Jae-Seong

2017-09-01

To evaluate the adverse effects of MeHg on the rotifer Brachionus koreanus and the copepod Paracyclopina nana, we assessed the effects of MeHg toxicity on life parameters (e.g. growth retardation and fecundity), antioxidant systems, and mitogen-activated protein kinase (MAPK) signaling pathways at various concentrations (1ng/L, 10ng/L, 100ng/L, 500ng/L, and 1000ng/L). MeHg exposure resulted in the growth retardation with the increased ROS levels but decreased glutathione (GSH) levels in a dose-dependent manner in both B. koreanus and P. nana. Antioxidant enzymatic activities (e.g. glutathione S-transferase [GST], glutathione reductase [GR], and glutathione peroxidase [GPx]) in B. koreanus showed more positive responses compared the control but in P. nana, those antioxidant enzymatic activities showed subtle changes due to different no observed effect concentration (NOEC) values among the two species. Expression of antioxidant genes (e.g. superoxide dismutase [SOD], GSTs, glutathione peroxidase [GPx], and catalase [CAT]) also demonstrated similar effects as shown in antioxidant enzymatic activities. In B. koreanus, the level of p-ERK was decreased in the presence of 1000ng/L MeHg, while the levels of p-ERK and p-p38 in P. nana were reduced in the presence of 10ng/L MeHg. However, p-JNK levels were not altered by MeHg in B. koreanus and P. nana, compared to the corresponding controls. In summary, life parameters (e.g. reduced fecundity and survival rate) were closely associated with effects on the antioxidant system in response to MeHg. These observations provide a better understanding on the adverse effects of MeHg on in vivo life parameters and molecular defense mechanisms in B. koreanus and P. nana. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

PubMed Central

Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

2014-01-01

Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[−]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(−) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

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

Obesity and type 2 diabetes risk in midadult life: the role of childhood adversity.

PubMed

Thomas, Claudia; Hyppönen, Elina; Power, Chris

2008-05-01

Child abuse has been associated with poorer physical health in adulthood, but less is known about childhood adversity more broadly, including neglect and family problems, or the pathways from adversity to adult disease. We have examined how different stressful emotional or neglectful childhood adversities are related to adiposity and glucose control in midadulthood, taking into account childhood factors, and whether the relationships are mediated by adult health behaviors and socioeconomic position. This was a prospective longitudinal study of 9310 members of the 1958 British birth cohort who participated in a biomedical interview at 45 years of age. Primary outcomes consisted of continuous measures of BMI, waist circumference, and glycosylated hemoglobin at 45 years and categorical indicators: total obesity (BMI > or = 30), central obesity (waist circumference: > or = 102 cm for men and > or = 88 cm for women), and glycosylated hemoglobin level of > or = 6. The risk of obesity increased by 20% to 50% for several adversities (physical abuse, verbal abuse, witnessed abuse, humiliation, neglect, strict upbringing, physical punishment, conflict or tension, low parental aspirations or interest in education, hardly takes outings with parents, and father hardly reads to child). Adversities with the strongest associations with adiposity (eg, physical abuse) tended to be associated with glycosylated hemoglobin levels of > or = 6, but in most cases associations were explained by adjustment for adulthood mediators such as adiposity. Effects of other adversities reflecting less severe emotional neglect and family environment were largely explained by childhood socioeconomic factors. Some childhood adversities increase the risk of obesity in adulthood and thereby increase the risk for type 2 diabetes. Research is needed to understand the interrelatedness of adversities, the social context of their occurrence, and trajectories from adversity to adult disease.

[Influence of OM-85 BV on hBD-1 and immunoglobulin in children with asthma and recurrent respiratory tract infection].

PubMed

Liao, Jia-Yi; Zhang, Tao

2014-05-01

To observe the clinical therapeutic effect of OM-85 BV(OM-85 Broncho-Vaxom) in children with asthma and recurrent respiratory tract infection, and the effect of OM-85 BV on human β-defensins 1 (hBD-1) and immunoglobulin levels. Sixty-two children with asthma and recurrent respiratory infection treated between 2011 January and December were divided into two groups by the randomized, double blind method: a treatment group and a control group. With inhaling corticosteroids, the treatment group was given OM-85 BV, and the control group was given a placebo. Clinical curative effects and adverse reactions were observed. Serum levels of hBD-1, IgA, IgG, IgM and urea and alanine aminotransferase (ALT) were measured before treatment and 6 months and 12 months after treatment. Compared with the control group and before treatment, the frequency of respiratory tract infection was reduced in the treatment group 6 months and 12 months after treatment (P<0.05), and serum levels of hBD-1, IgA and IgG in the treatment group increased significantly (P<0.05). There was no significant difference in serum levels of urea, ALT and IgM between the control and treatment groups (P>0.05). Mild adverse reactions occurred in 3 cases in the two groups, 2 cases of abdominal pain and 1 cases of constipation. OM-85 BV can improve serum levels of hBD-1, IgA and IgG, reduce the occurrence of acute respiratory tract infection and cause mild adverse reactions, suggesting its satisfactory therapeutic effect and safety in the treatment of asthma combined with recurrent respiratory tract infection in children.

Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.

PubMed

Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

2013-03-01

This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.

Chromium levels in insulin-sensitive tissues and the thigh bone are modulated by prednisolone and high-fat diets in mice.

PubMed

Chen, Po-Wen; Lin, Chang; Chen, Chung-De; Chen, Wen-Ying; Mao, Frank Chiahung

2013-04-01

Glucocorticoids (GCs) are often prescribed in clinics but many adverse effects are also attributed to GCs. It is important to determine the role of GCs in the development of those adverse effects. Here, we investigated the impact of GCs on trivalent chromium (Cr) distribution in animals. Cr has been proposed to be important for proper insulin sensitivity, and deficits may lead to disruption of metabolism. For comparison, the effect of a high-fat diet on Cr modulation was also evaluated. C57BL/6JNarl mice were fed regular or high-fat diets for 12 weeks and further grouped for treatment with prednisolone or saline. Cr levels in tissues were determined 12 h after the treatments. Interestingly, prednisolone treatment led to significantly reduced Cr levels in fat tissue in mice fed regular diets; compared to the high-fat diet alone, prednisolone plus the high-fat diet led to a further reduction in Cr levels in the liver, muscle, and fat. Notably, a single dose of prednisolone was linked with elevated Cr levels in the thigh bones of mice fed by either regular or high-fat diets. In conclusion, this report has provided evidence that prednisolone in combination with a high-fat diet effects modulation of Cr levels in selected tissues.

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use

PubMed Central

Kinoshita, Yoshikazu; Ishimura, Norihisa; Ishihara, Shunji

2018-01-01

Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies. PMID:29605975

Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use.

PubMed

Kinoshita, Yoshikazu; Ishimura, Norihisa; Ishihara, Shunji

2018-04-30

Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.

Local weather conditions have complex effects on the growth of blue tit nestlings.

PubMed

Mainwaring, Mark C; Hartley, Ian R

2016-08-01

Adverse weather conditions are expected to result in impaired nestling development in birds, but empirical studies have provided equivocal support for such a relationship. This may be because the negative effects of adverse weather conditions are masked by parental effects. Globally, ambient temperatures, rainfall levels and wind speeds are all expected to increase in a changing climate and so there is a need for a better understanding of the relationship between weather conditions and nestling growth. Here, we describe a correlative study that examined the relationships between local temperatures, rainfall levels and wind speeds and the growth of individual blue tit (Cyanistes caeruleus) nestlings in relation to their hatching order and sex. We found that changes in a range of morphological characters were negatively related to both temperature and wind speed, but positively related to rainfall. These patterns were further influenced by the hatching order of the nestlings but not by nestling sex. This suggests that the predicted changes in local weather conditions may have complex effects on nestling growth, but that parents may be able to mitigate the adverse effects via adaptive parental effects. We therefore conclude that local weather conditions have complex effects on avian growth and the implications for patterns of avian growth in a changing climate are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medication errors: the role of the patient.

PubMed

Britten, Nicky

2009-06-01

1. Patients and their carers will usually be the first to notice any observable problems resulting from medication errors. They will probably be unable to distinguish between medication errors, adverse drug reactions, or 'side effects'. 2. Little is known about how patients understand drug related problems or how they make attributions of adverse effects. Some research suggests that patients' cognitive models of adverse drug reactions bear a close relationship to models of illness perception. 3. Attributions of adverse drug reactions are related to people's previous experiences and to their level of education. The evidence suggests that on the whole patients' reports of adverse drug reactions are accurate. However, patients do not report all the problems they perceive and are more likely to report those that they do perceive as severe. Patients may not report problems attributed to their medications if they are fearful of doctors' reactions. Doctors may respond inappropriately to patients' concerns, for example by ignoring them. Some authors have proposed the use of a symptom checklist to elicit patients' reports of suspected adverse drug reactions. 4. Many patients want information about adverse drug effects, and the challenge for the professional is to judge how much information to provide and the best way of doing so. Professionals' inappropriate emphasis on adherence may be dangerous when a medication error has occurred. 5. Recent NICE guidelines recommend that professionals should ask patients if they have any concerns about their medicines, and this approach is likely to yield information conducive to the identification of medication errors.

Safety organizing, emotional exhaustion, and turnover in hospital nursing units.

PubMed

Vogus, Timothy J; Cooil, Bruce; Sitterding, Mary; Everett, Linda Q

2014-10-01

Prior research has found that safety organizing behaviors of registered nurses (RNs) positively impact patient safety. However, little research exists on how engaging in safety organizing affects caregivers. While we know that organizational processes can have divergent effects on organizational and employee outcomes, little research exists on the effects of pursuing highly reliable performance through safety organizing on caregivers. Specifically, we examined whether, and the conditions under which, safety organizing affects RN emotional exhaustion and nursing unit turnover rates. Subjects included 1352 RNs in 50 intensive care, internal medicine, labor, and surgery nursing units in 3 Midwestern acute-care hospitals who completed questionnaires between August and December 2011 and 50 Nurse Managers from the units who completed questionnaires in December 2012. Cross-sectional analyses of RN emotional exhaustion linked to survey data on safety organizing and hospital incident reporting system data on adverse event rates for the year before survey administration. Cross-sectional analysis of unit-level RN turnover rates for the year following the administration of the survey linked to survey data on safety organizing. Multilevel regression analysis indicated that safety organizing was negatively associated with RN emotional exhaustion on units with higher rates of adverse events and positively associated with RN emotional exhaustion with lower rates of adverse events. Tobit regression analyses indicated that safety organizing was associated with lower unit level of turnover rates over time. Safety organizing is beneficial to caregivers in multiple ways, especially on nursing units with high levels of adverse events and over time.

Zhibitai and low-dose atorvastatin reduce blood lipids and inflammation in patients with coronary artery disease.

PubMed

Zhao, Yuhong; Peng, Ran; Zhao, Wang; Liu, Qiong; Guo, Yuan; Zhao, Shuiping; Xu, Danyan

2017-02-01

Atorvastatin decreases blood lipids but is associated with side effects. Zhibitai is a traditional Chinese medicine used to treat blood lipid disorders. The objective of this study is to evaluate the lipid-lowering effect, antiinflammatory effect, and adverse events of zhibitai combined to atorvastatin in patients with coronary heart diseases (CHDs). Patients with CHD (n = 150) were randomized to: zhibitai 480 mg + atorvastatin 10 mg (ZA10 group), atorvastatin 20 mg (A20 group), and atorvastatin 40 mg (A40 group). Lipid profile, cardiotrophin-1 (CT-1), and C-reactive protein (CRP) were measured after 4 and 8 weeks of treatment. Self-reported side effects, liver function, kidney function, and creatine kinase levels were monitored. After 8 weeks, triglycerides, total cholesterol (TC), LDL-cholesterol (LDL-C), and apolipoprotein B100 (ApoB100) levels were decreased in the ZA10 group (-64%, -37%, -46%, and -54%, respectively, compared with baseline), and these changes were similar to those of the A40 group (P > 0.05). CT-1 and high sensitivity-C reactive protein (hs-CRP) levels were significantly decreased in the ZA10 group after 4 and 8 weeks (4 weeks: -73% and 96%; 8 weeks: -89% and -98%; all P < 0.01), without differences among the 3 groups (P > 0.05). After 8 weeks of treatment, adverse events (abdominal distention, nausea, vomiting, and hunger) were found in 4, 5, and 7 patients in the ZA10, A20, and A40 groups, respectively. ZA10 significantly reduced triglycerides, TC, LDL-C, ApoB, CT-1, and hs-CRP levels in patients with CHD, similar to the effects of A40 and A20, but ZA10 lead to fewer adverse events.

40 CFR 141.11 - Maximum contaminant levels for inorganic chemicals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... levels that exceed 10 mg/l; and (4) No adverse health effects shall result. [40 FR 59570, Dec. 24, 1975... arsenic applies only to community water systems. The analyses and determination of compliance with the 0...) The maximum contaminant level for arsenic is 0.05 milligrams per liter for community water systems...

Childhood social adversity and risk of depressive symptoms in adolescence in a US national sample.

PubMed

Björkenstam, Emma; Pebley, Anne R; Burström, Bo; Kosidou, Kyriaki

2017-04-01

Childhood social adversity has been associated with an increased risk of depression and other psychiatric disorders in adolescence and early adulthood. However, the role of timing and accumulation of adversities has not yet been established in longitudinal studies. We examined the association between childhood adversities and adolescent depressive symptoms, and the impact of timing and accumulation of adversity. Longitudinal data were obtained from the Child Development Supplement to the Panel Study of Income Dynamics (n=2223), a nationally representative survey of US families that incorporates data from parents and their children. Negative binomial regression analysis was used to estimate effects of childhood social adversity on adolescent depressive symptoms, presented as Incidence Rate Ratios with 95% confidence intervals. Children exposed to social adversity reported higher levels of adolescent depressive symptoms captured by two depression scales. Single-parent household and residential instability were particularly associated with depressive symptoms. A positive relationship was found between cumulative adversity and the risk of adolescent depression. The timing of exposure appeared to have little effect on the risk of adolescent depressive symptoms. The structure of the data implies that alternative causal pathways cannot be fully discounted. The self- or parent-reported data is subject to recall bias. Our findings support the long-term negative impact of childhood adversity on adolescent depressive symptoms, regardless of when in childhood the adversity occurs. Policies and interventions to reduce adolescent depressive symptoms need to consider the social background of the family as an important risk or protective factor. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrative data mining of high-throughput in vitro screens, in vivo data, and disease information to identify Adverse Outcome Pathway (AOP) signatures:ToxCast high-throughput screening data and Comparative Toxicogenomics Database (CTD) as a case study.

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework provides a systematic way to describe linkages between molecular and cellular processes and organism or population level effects. The current AOP assembly methods however, are inefficient. Our goal is to generate computationally-pr...

BEHAVIOR OF PERSISTENT BIOACCUMULATIVE TOXICANTS IN FISH EARLY LIFE STAGES

EPA Science Inventory

Whether through environmental criteria or site-specific risk assessments, many EPA programs rely on linking environmental exposures to levels of adverse effect (or no effect) in fish and wildlife. While empirical relationships of exposure to effect can be used for such assessmen...

Area-level risk factors for adverse birth outcomes: trends in urban and rural settings.

PubMed

Kent, Shia T; McClure, Leslie A; Zaitchik, Ben F; Gohlke, Julia M

2013-06-10

Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban-rural status. Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991-2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse birth outcomes elsewhere may not be reaching isolated rural areas.

40 CFR 798.4350 - Inhalation developmental toxicity study.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue... million (ppm). (6) “No-observed-effect level” is the maximum concentration in a test which produces no observed adverse effects. A no-observed-effect level is expressed in terms of weight or volume of test...

40 CFR 798.4350 - Inhalation developmental toxicity study.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue... million (ppm). (6) “No-observed-effect level” is the maximum concentration in a test which produces no observed adverse effects. A no-observed-effect level is expressed in terms of weight or volume of test...

40 CFR 798.4350 - Inhalation developmental toxicity study.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue... million (ppm). (6) “No-observed-effect level” is the maximum concentration in a test which produces no observed adverse effects. A no-observed-effect level is expressed in terms of weight or volume of test...

Patterns of benzylpiperazine/trifluoromethylphenylpiperazine party pill use and adverse effects in a population sample in New Zealand.

PubMed

Wilkins, Chris; Sweetsur, Paul; Girling, Melissa

2008-11-01

A large legal market for party pills containing benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) developed in New Zealand after 2004. The use of these party pills has been associated with adverse health effects. The purpose of this paper was to assess a general population sample of party pill users to investigate the relationship between (1) patterns of use of BZP/TFMPP party pills and concurrent use of other drug types, and (2) adverse side effects from BZP/TFMPP party pill use. A national household survey of the use of BZP/TFMPP party pills was conducted using a computer-assisted telephone interviewing (CATI) facility. The quantity of BZP and TFMPP in each brand of party pill was obtained from the National Poisons Centre. Multiple logistic regression analysis was used to identify independent predictors of having experienced adverse side effects from party pills. The mean quantity of BZP/TFMPP taken on an occasion of greatest use was 533 mg (median 400 mg, range 43-2500 mg). Being female, using cannabis and other drugs concurrently with BZP/TFMPP party pills, taking large quantities of party pills in a single session and taking 5-hydroxytryptophan (5-HTP) recovery pills at the same time as party pills were independent predictors of having experienced an adverse problem from party pills. Females may be at greater risk of experiencing problems from BZP/TFMPP party pills due to their smaller physical size. Taking 5-HTP 'recovery' pills with party pills may increase the risk of adverse effects as both substances increase users' levels of serotonin.

Safety of purified decolorized (low anthraquinone) whole leaf Aloe vera (L) Burm. f. juice in a 3-month drinking water toxicity study in F344 rats.

PubMed

Shao, A; Broadmeadow, A; Goddard, G; Bejar, E; Frankos, V

2013-07-01

Decolorized (purified, low anthraquinone) whole leaf Aloe vera (L.) Burm. f. juice was administered at concentrations of 0%, 0.5%, 1% and 2% in the drinking water of F344Du rats for 3 months without any adverse effect. The no-observed-adverse-effect level (NOAEL) in this study was considered to be >2%w/v (>1845 mg/kg bodyweight/day for males and >2920 mg/kg bodyweight for females). The test material contained total anthraquinones at <0.1 parts per million. In the present study there was a complete absence of any histological alteration in samples from the cecum, colon (proximal, mid and distal regions). Similar concentrations of non-decolorized (unpurified, high anthraquinone) Aloe vera extracts tested in other studies have resulted in an increased incidence and severity of diarrhea and colon adenomas and carcinomas. The results of this study supports the assertion that the high levels of anthraquinone present in orally administered, non-purified whole leaf Aloe vera extract may be responsible for the adverse effects observed on the colon. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gestational bisphenol A exposure and testis development.

PubMed

Williams, Cecilia; Bondesson, Maria; Krementsov, Dimitry N; Teuscher, Cory

Virtually all humans are exposed to bisphenol A (BPA). Since BPA can act as a ligand for estrogen receptors, potential hazardous effects of BPA should be evaluated in the context of endogenous estrogenic hormones. Because estrogen is metabolized in the placenta, developing fetuses are normally exposed to very low endogenous estrogen levels. BPA, on the other hand, passes through the placenta and might have distinct adverse consequences during the sensitive stages of fetal development. Testicular gametogenesis and steroidogenesis begin early during fetal development. These processes are sensitive to estrogens and play a role in determining the number of germ stem cells, sperm count, and male hormone levels in adulthood. Although studies have shown a correlation between BPA exposure and perturbed reproduction, a clear consensus has yet to be established as to whether current human gestational BPA exposure results in direct adverse effects on male genital development and reproduction. However, studies in animals and in vitro have provided direct evidence for the ability of BPA exposure to influence male reproductive development. This review discusses the current knowledge of potential effects of BPA exposure on male reproductive health and whether gestational exposure adversely affects testis development.

Mitigating adverse event reporting bias in spine surgery.

PubMed

Auerbach, Joshua D; McGowan, Kevin B; Halevi, Marci; Gerling, Michael C; Sharan, Alok D; Whang, Peter G; Maislin, Greg

2013-08-21

Recent articles in the lay press and literature have raised concerns about the ability to report honest adverse event data from industry-sponsored spine surgery studies. To address this, clinical trials may utilize an independent Clinical Events Committee (CEC) to review adverse events and readjudicate the severity and relatedness accordingly. We are aware of no prior study that has quantified either the degree to which investigator bias is present in adverse event reporting or the effect that an independent CEC has on mitigating this potential bias. The coflex Investigational Device Exemption study is a prospective randomized controlled trial comparing coflex (Paradigm Spine) stabilization with lumbar spinal fusion to treat spinal stenosis and spondylolisthesis. Investigators classified the severity of adverse events (mild, moderate, or severe) and their relationship to the surgery and device (unrelated, unlikely, possibly, probably, or definitely). An independent CEC, composed of three spine surgeons without affiliation to the study sponsor, reviewed and reclassified all adverse event reports submitted by the investigators. The CEC reclassified the level of severity, relation to the surgery, and/or relation to the device in 394 (37.3%) of 1055 reported adverse events. The proportion of adverse events that underwent reclassification was similar in the coflex and fusion groups (37.9% compared with 36.0%, p = 0.56). The CEC was 5.3 (95% confidence interval [CI], 2.6 to 10.7) times more likely to upgrade than downgrade the adverse event. The CEC was 7.3 (95% CI, 5.1 to 10.6) times more likely to upgrade than downgrade the relationship to the surgery and 11.6 (95% CI, 7.5 to 18.8) times more likely to upgrade than downgrade the relationship to the device. The status of the investigator's financial interest in the company had little effect on the reclassification of adverse events. Thirty-seven percent of adverse events were reclassified by the CEC; the large majority of the reclassifications were an upgrade in the level of severity or a designation of greater relatedness to the surgery or device. An independent CEC can identify and mitigate potential inherent investigator bias and facilitate an accurate assessment of the safety profile of an investigational device, and a CEC should be considered a requisite component of future clinical trials.

A risk assessment of topical tretinoin as a potential human developmental toxin based on animal and comparative human data.

PubMed

Johnson, E M

1997-03-01

Although topically applied all-trans-retinoic acid (tretinoin) undergoes minimal absorption and adds negligibly to normal endogenous levels, its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks. To assess the actual potential for developmental toxicity from treatment with topical tretinoin. Risk assessments were conducted on four known human developmental toxicants (valproic acid, methotrexate, thalidomide, and isotretinoin) and a potential developmental toxicant (acetylsalicylic acid). The margin of safety for each chemical was calculated from the ratio of animal no-observed adverse effect levels to human lowest-observed adverse effect levels or estimated exposure doses. The derived safety margin of more than 100 for topical tretinoin (with 2% absorption) contrasted sharply with the near unity values for valproic acid, methotrexate, thalidomide, and isotretinoin and was larger than that for acetylsalicylic acid. These data support other epidemiologic and animal data that topical tretinoin is not a potential human developmental toxicant.

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem

PubMed Central

2014-01-01

Background Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? Methods We used cross-sectional data from 3,064 males and females aged 12–19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Results Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Conclusions Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries. PMID:25210535

Gender Differences in the Physical and Psychological Manifestation of Childhood Trauma and/or Adversity in People with Psychosis.

PubMed

Sweeney, Shaun; Air, Tracy; Zannettino, Lana; Galletly, Cherrie

2015-01-01

The link between childhood trauma and/or adversity and risk of psychosis is well known. Our aim was to determine the prevalence of childhood trauma and/or adversity in people who have psychotic disorders and to investigate the association between childhood trauma and/or adversity and a range of social and health measures. Participants (n = 391, 42% male) were specifically asked about any experience of childhood trauma and/or adversity. Respondents provided information about education, employment, physical health, and health service utilization. Univariate analyses revealed that childhood trauma and/or adversity was associated with poorer levels of self-reported physical health and social problems. This includes the experience of chronic pain, headaches, arthritis, asthma, and victimization/stigma in men. Participants with a childhood trauma and/or adversity history indicated higher rates of lifetime suicide attempts with women reporting more lifetime depressive symptoms. Multivariate analyses revealed differing profiles in relation to physical and psychological health variable between males and females. Males with the experience of childhood trauma and/or adversity were significantly more likely to report cardiovascular/stroke issues, migraines and anhedonia. Females with the experience of childhood trauma and/or adversity were more likely to report a lifetime history of elevated mood and to be married or in a de facto relationship. There has been very little research into the assessment and treatment of the effects of childhood trauma and/or adversity in adults with psychosis. Childhood trauma and/or adversity may contribute to higher rates of self-reported poor health in men and is associated with increased depression in women. Our findings suggest that interventions to address the effects of past trauma are urgently needed.

Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community: A Single-center Experience.

PubMed

Ali, Naveed; Malik, Faizan; Jafri, Syed Imran Mustafa; Naglak, Mary; Sundermeyer, Mark; Pickens, Peter V

2017-07-01

Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels. The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologist's assessment and evaluated independently using the response criteria for each B-cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B-cell malignancies and receiving ibrutinib therapy were eligible. The median age was 73 years (range, 49-96 years), and 84.4% of the patients had received ≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7 × 10 3 cells/μL). Although the IgG levels at 3, 6, and 12 months had decreased (P = .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5, P = .3, and P = .9, respectively). Ibrutinib is a highly effective and tolerable drug for B-cell malignancies in the general community. In contrast to the previously reported rate of 5% to 7%, we observed a higher rate (11%) of atrial fibrillation, which might have resulted from the smaller sample size in the present study and the multiple comorbidities. Nonetheless, this treatment-limiting side effect requires further elucidation. Paradoxical lymphocytosis at the outset of therapy was a common and benign finding. In conjunction with the reported trials, the IgG levels decreased in the first year of continued therapy. However, the IgA levels did not increase, even after 2 years of therapy. Published by Elsevier Inc.

Adverse events associated with acupuncture: three multicentre randomized controlled trials of 1968 cases in China.

PubMed

Zhao, Ling; Zhang, Fu-wen; Li, Ying; Wu, Xi; Zheng, Hui; Cheng, Lin-hao; Liang, Fan-rong

2011-03-24

In order to evaluate the safety of acupuncture in China objectively, we investigated the adverse events associated with acupuncture based on three multicentre randomized controlled trials (RCTs) to assess the safety of acupuncture, identifying the common types of acupuncture adverse events, and analysing the related risk factors for their occurrence. This observational study included patients who received acupuncture from three multicentre RCTs respectively for migraine, functional dyspepsia and Bell's palsy. The 1968 patients and their acupuncturists documented adverse events associated with acupuncture after treatment. We collected data about adverse events due to acupuncture treatment from their case report forms. We analysed the incidence and details of the adverse effects, and studied the risk factors for acupuncture adverse events with non-conditional logistic regression analysis. Among the 1968 patients, 74 patients (3.76%) suffered at least one adverse event throughout the treatment period. We did not observe the occurrence of serious adverse events. 73 patients with adverse events recovered within 2 weeks through effective treatment such as physiotherapy or self-treatment. A total of 3 patients withdrew because of adverse events. There were 9 types of adverse events related to acupuncture, including subcutaneous haematoma, bleeding, skin bruising and needle site pain. Subcutaneous haematoma and haemorrhage in the needling points were the most common adverse events. Age and gender were related to the occurrence of acupuncture adverse events. The older the patients were, the higher the risk of adverse events was. In addition, male patients had slightly higher risk of an adverse event than female patients. Acupuncture is a safe therapy with low risk of adverse events in clinical practice. The risk factors for adverse events (AEs) were related to the patients' gender and age and the local anatomical structure of the acupoints. AEs could be reduced and mitigated by improving the medical environment, ensuring a high technical level of the acupuncture practitioners and establishing a good relationship of mutual trust between doctor and patient. ClinicalTrials.gov: NCT00599586, NCT00599677, NCT00608660.

Allostasis and Allostatic Load in the Context of Poverty in Early Childhood

PubMed Central

Blair, Clancy; Raver, Cybele; Granger, Douglas; Mills-Koonce, Roger; Hibel, Leah

2014-01-01

This paper examined the relation of early environmental adversity associated with poverty to child resting or basal level of cortisol in a prospective longitudinal sample of 1,135 children seen at 7, 15, 24, 35, and 48 months of age. We found main effects for length of time in poverty, poor housing quality, African American ethnicity, and low positive caregiving behavior in which each was uniquely associated with an overall higher level of cortisol from age 7 months to 48 months. We also found that two aspects of the early environment in the context of poverty, adult exits from the home and perceived economic insufficiency, were related to salivary cortisol in a time dependent manner. The effect for the first of these, exits from the home, was consistent with the principle of allostatic load in which the effects of adversity on stress physiology accumulate over time. The effect for perceived economic insufficiency was one in which insufficiency was associated with higher levels of cortisol in infancy but with a typical but steeper decline in cortisol with age at subsequent time points. PMID:21756436

Proximal muscular atrophy and weakness: An unusual adverse effect of deferasirox iron chelation therapy.

PubMed

Vill, K; Müller-Felber, W; Teusch, V; Blaschek, A; Gerstl, L; Huetker, S; Albert, M H

2016-01-01

Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug. Copyright © 2016 Elsevier B.V. All rights reserved.

The need for congressional action to finance arsenic reductions in drinking water.

PubMed

Levine, Rebecca Leah

2012-11-01

Many public water systems in the U.S. are unsafe because the communities cannot afford to comply with the current 10 parts per billion (ppb) federal arsenic standard for drinking water. Communities unable to afford improvements remain vulnerable to adverse health effects associated with higher levels of arsenic exposure. Scientific and bipartisan political consensus exists that the arsenic standard should not be less stringent than 10 ppb, and new data suggest additional adverse health effects related to arsenic exposure through drinking water. Congress has failed to reauthorize the Drinking Water State Revolving Fund program to provide reliable funding to promote compliance and reduce the risk of adverse health effects. Congress's recent ad hoc appropriations do not allow long-term planning and ongoing monitoring and maintenance. Investing in water infrastructure will lower health care costs and create American jobs. Delaying necessary upgrades will only increase the costs of improvements over time.

Screening Chemical Effects on Steroidogenesis in H295R Human Adrenocortical Carcinoma Cells (SOT)

EPA Science Inventory

Proper endocrine function requires steroid hormone biosynthesis and metabolism (steroidogenesis). Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. This study is the first to estab...

Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events

PubMed Central

2013-01-01

Background To address knowledge gaps regarding natural health product (NHP) usage in mental health populations, we examined their use in adults with mood disorders, and explored the potential for adverse events. Methods Food and NHP intake was obtained from 97 adults with mood disorders. NHP data was used to compare prevalence with population norms (British Columbia Nutrition Survey; BCNS). Bivariate and regression analyses examined factors associated with NHP use. Assessment of potential adverse effects of NHP use was based on comparing nutrient intakes from food plus supplements with the Dietary Reference Intakes and by reviewing databases for reported adverse health effects. Results Two-thirds (66%; 95% CI 56 to 75) were taking at least one NHP; 58% (95% CI 47 to 68) were taking NHPs in combination with psychiatric medications. The proportion of each type of NHP used was generally higher than the BCNS (range of p’s < 0.05 to 0.0001). When intakes from food and NHP sources were combined, a small proportion exceeded any Lowest-Observed-Adverse-Effect-Levels: only for niacin (n = 17) and magnesium (n = 6), two nutrients for which the potential for adverse effects is minimal. Conversely, about 38% (95% CI 28 to 49) of the sample were taking a non-nutrient based NHP for which previous adverse events had been documented. Conclusions The prevalent use of NHPs in this population suggests that health care providers need to be knowledgeable about their characteristics. The efficacy and safety of NHPs in relation to mental health warrants further investigation. PMID:23570306

The household food insecurity gradient and potential reductions in adverse population mental health outcomes in Canadian adults.

PubMed

Jessiman-Perreault, Geneviève; McIntyre, Lynn

2017-12-01

Household food insecurity is related to poor mental health. This study examines whether the level of household food insecurity is associated with a gradient in the risk of reporting six adverse mental health outcomes. This study further quantifies the mental health impact if severe food insecurity, the extreme of the risk continuum, were eliminated in Canada. Using a pooled sample of the Canadian Community Health Survey (N = 302,683), we examined the relationship between level of food insecurity, in adults 18-64 years, and reporting six adverse mental health outcomes. We conducted a probit analysis adjusted for multi-variable models, to calculate the reduction in the odds of reporting mental health outcomes that might accrue from the elimination of severe food insecurity. Controlling for various demographic and socioeconomic covariates, a food insecurity gradient was found in six mental health outcomes. We calculated that a decrease between 8.1% and 16.0% in the reporting of these mental health outcomes would accrue if those who are currently severely food insecure became food secure, after controlling for covariates. Household food insecurity has a pervasive graded negative effect on a variety of mental health outcomes, in which significantly higher levels of food insecurity are associated with a higher risk of adverse mental health outcomes. Reduction of food insecurity, particularly at the severe level, is a public health concern and a modifiable structural determinant of health worthy of macro-level policy intervention.

Childhood bullying involvement predicts low-grade systemic inflammation into adulthood

PubMed Central

Copeland, William E.; Wolke, Dieter; Lereya, Suzet Tanya; Shanahan, Lilly; Worthman, Carol; Costello, E. Jane

2014-01-01

Bullying is a common childhood experience that involves repeated mistreatment to improve or maintain one’s status. Victims display long-term social, psychological, and health consequences, whereas bullies display minimal ill effects. The aim of this study is to test how this adverse social experience is biologically embedded to affect short- or long-term levels of C-reactive protein (CRP), a marker of low-grade systemic inflammation. The prospective population-based Great Smoky Mountains Study (n = 1,420), with up to nine waves of data per subject, was used, covering childhood/adolescence (ages 9–16) and young adulthood (ages 19 and 21). Structured interviews were used to assess bullying involvement and relevant covariates at all childhood/adolescent observations. Blood spots were collected at each observation and assayed for CRP levels. During childhood and adolescence, the number of waves at which the child was bullied predicted increasing levels of CRP. Although CRP levels rose for all participants from childhood into adulthood, being bullied predicted greater increases in CRP levels, whereas bullying others predicted lower increases in CRP compared with those uninvolved in bullying. This pattern was robust, controlling for body mass index, substance use, physical and mental health status, and exposures to other childhood psychosocial adversities. A child’s role in bullying may serve as either a risk or a protective factor for adult low-grade inflammation, independent of other factors. Inflammation is a physiological response that mediates the effects of both social adversity and dominance on decreases in health. PMID:24821813

Childhood bullying involvement predicts low-grade systemic inflammation into adulthood.

PubMed

Copeland, William E; Wolke, Dieter; Lereya, Suzet Tanya; Shanahan, Lilly; Worthman, Carol; Costello, E Jane

2014-05-27

Bullying is a common childhood experience that involves repeated mistreatment to improve or maintain one's status. Victims display long-term social, psychological, and health consequences, whereas bullies display minimal ill effects. The aim of this study is to test how this adverse social experience is biologically embedded to affect short- or long-term levels of C-reactive protein (CRP), a marker of low-grade systemic inflammation. The prospective population-based Great Smoky Mountains Study (n = 1,420), with up to nine waves of data per subject, was used, covering childhood/adolescence (ages 9-16) and young adulthood (ages 19 and 21). Structured interviews were used to assess bullying involvement and relevant covariates at all childhood/adolescent observations. Blood spots were collected at each observation and assayed for CRP levels. During childhood and adolescence, the number of waves at which the child was bullied predicted increasing levels of CRP. Although CRP levels rose for all participants from childhood into adulthood, being bullied predicted greater increases in CRP levels, whereas bullying others predicted lower increases in CRP compared with those uninvolved in bullying. This pattern was robust, controlling for body mass index, substance use, physical and mental health status, and exposures to other childhood psychosocial adversities. A child's role in bullying may serve as either a risk or a protective factor for adult low-grade inflammation, independent of other factors. Inflammation is a physiological response that mediates the effects of both social adversity and dominance on decreases in health.

[Effects of excess nicotinic acid on growth and the urinary excretion of B-group vitamins and the metabolism of tryptophan in weaning rats].

PubMed

Fukuwatari, Tsutomu; Kurata, Kaori; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake level of nicotinic acid in humans, we investigated the effects of excess nicotinic acid administration on body weight gain, food intake, and urinary excretion of water-soluble vitamins and the metabolism of tryptophan in weaning rats. The weaning rats were freely fed a niacin-free 20% casein diet (control diet) or the same diet with 0.1%, 0.3% or 0.5% nicotinic acid for 23 days. The excess nicotinic acid intake did not affect body weight gain, food intake, serotonin contents in the brain, stomach and small intestine, or the urinary excretions of water-soluble vitamins. Although excess nicotinic acid did not affect the upper part of the tryptophan-nicotinamide pathway, 0.5% nicotinic acid diet increased the urinary excretion of quinolinic acid. The diet containing more than 0.3% nicotinic acid also increased the urinary excretion of nicotinic acid, which is usually below the limit of detection. As determined from the results of body weight gain and food intake as indices for apparent adverse effects, the no-observed-adverse-effect-level (NOAEL) for nicotinic acid was 0.5% in diet, corresponding to 450 mg/kg body weight/day. As judged from in increase of urinary quinolinic acid and nicotinic acid as indices of metabolic change, NOAEL was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and the lowest-observed-adverse-effect-level (LOAEL) was 0.3% in diet, corresponding to 270 mg/kg body weight/day.

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

Johnson, E.M.

Human reproduction and development is a cycle of interdependent events. Virtually all of its phases have been shown to be the primary target of one or more non-mutagenic exogenous agents. Such agents interfere with certain of the countless epigenetic or ontogenic events essential for normal completion of the cycle. Mutagens disrupt this cycle at some points, but the overwhelming majority of reproductive and developmental toxins are not mutagenic. As in all aspects of toxicology, the reproductive and developmental effects of chemicals are determined by the intrinsic nature of the chemical, the quantity of the chemical exposure, the duration of exposuremore » and the stage of the cycle at which it occurs. Signs of reproductive toxicity range from reduced fertility to spontaneous abortion. Adverse effects on the conceptus are categorized as functional deficits, developmental retardation, structural abnormality and death. One or more of these is anticipated to occur as a result of excess exposure to most chemicals. Although the degree of hazard and risk potential can be calculated in each instance, chemicals differ markedly in their ability to interfere with reproduction and/or development. Standardized methods for reproductive and developmental toxicity safety evaluation are available for detecting adverse effects upon any aspect of reproduction and development. Data currently available establish that these state-of-the-art tests conducted in laboratory animals are often highly predictive of the type of adverse effect a particular chemical will have in humans, as well as the exposure level at which it will occur. By adding a modest safety factor to the no-observed-effect-level of well-executed animal studies, safe human exposure levels can be established. 40 references.« less

The Role of Fructose, Sucrose and High-fructose Corn Syrup in Diabetes.

PubMed

Cozma, Adrian I; Sievenpiper, John L

2014-02-01

Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. High-fructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecological studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugar-sweetened beverages, these associations are small, do not hold at moderate levels of intake and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructose-containing sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycaemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research.

The Role of Fructose, Sucrose and High-fructose Corn Syrup in Diabetes

PubMed Central

Cozma, Adrian I

2014-01-01

Abstract Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. High-fructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecological studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugar-sweetened beverages, these associations are small, do not hold at moderate levels of intake and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructose-containing sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycaemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research. PMID:29872464

Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles across the Lifespan

PubMed Central

Zilioli, Samuele; Slatcher, Richard B.; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

2016-01-01

Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here we tested whether childhood adversity was associated with diurnal cortisol parameters, and whether this link was partially explained by self-esteem. In both adults and children, childhood adversity was associated with lower levels of cortisol at awakening and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Lastly, those youth who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared to those youth whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the lifespan. PMID:27481911

Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

PubMed

Zilioli, Samuele; Slatcher, Richard B; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

2016-09-01

Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here, we tested whether childhood adversity was associated with diurnal cortisol parameters and whether this link was partially explained by self-esteem. In both adults and youths, childhood adversity was associated with lower levels of cortisol at awakening, and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Finally, youths who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared with youths whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the life span. © The Author(s) 2016.

Attachment-Related Regulatory Processes Moderate the Impact of Adverse Childhood Experiences on Stress Reaction in Borderline Personality Disorder.

PubMed

Ehrenthal, Johannes C; Levy, Kenneth N; Scott, Lori N; Granger, Douglas A

2018-01-01

In this study, the authors explored whether attachment insecurity moderates the effects of adverse childhood experiences on stress reactivity in the context of borderline personality disorder (BPD). Participants were 113 women (39 with BPD, 15 with some BPD criteria present, 59 without any BPD symptoms) who participated in the Trier Social Stress Test. Saliva samples were collected before and after the stressor and assayed for salivary alpha-amylase (sAA) and cortisol. Adverse childhood experiences were measured using the Childhood Trauma Questionnaire, and attachment by the Experiences in Close Relationships-Revised questionnaire. Results revealed that attachment avoidance and a combination of more adverse childhood experiences and attachment insecurity resulted in higher sAA levels and differences in reactivity to the stressor. Interactions between attachment anxiety and adverse childhood experiences were related to blunted cortisol reactivity. The results suggest that the influence of adverse childhood experiences on stress regulation in BPD may be moderated by attachment-related regulatory processes.

Clinical Use of Aromatase Inhibitors in Adult Males.

PubMed

Tan, Ronny B W; Guay, Andre T; Hellstrom, Wayne J G

2014-04-01

There is a growing interest in the treatment of late-onset hypogonadism, another name for the study of testosterone deficiency in an older age group. Initial attempts at testosterone replacement have also brought attention to the possible adverse effects on the patients' cardiovascular risk factors and their prostate health. The "female" hormone estradiol is no longer considered as the feminizing hormone, as it has been identified to have an effect on the sexual and general well-being of adult males. Urologists and endocrinologists alike have started to pay attention to the serum T/E 2 (testosterone : estradiol) ratio that appears to be more important than the respective individual hormonal levels. Therein lies the possible role of aromatase inhibitors (AIs) in restoring the normal balance of serum testosterone and estradiol levels for the adequate treatment of late-onset hypogonadism, while limiting the potential adverse effects. Currently, other established clinical indications of AIs include the treatment of breast cancer in female patients and developmental growth problems in pediatric patients. This review evaluates the role of AIs as a treatment option for late-onset hypogonadism and the evidence for its other clinical uses in men, including its possible adverse effects. A literature review was performed with regards to the use of aromatase inhibitors in adult males, the role of estrogens in adult males, as well as adverse effect of AIs on bone health in adult males. To evaluate the evidence for the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, and male subfertility. To evaluate the evidence for the possible adverse effects on the bone health of adult males with the use of AIs. Currently there is no literature to recommend the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, or male subfertility, although some positive effects have been reported. The adverse effects on bone health seen in females treated with AIs are not seen in males. With the better understanding of the T/E 2 ratio in adult males, the lack of scientific data to show that bone health is adversely affected by AI usage in adult males, the positive effects of AIs on the treatment of conditions like late-onset hypogonadism and male subfertility encourages conducting large-scale, multicenter, randomized controlled trials for the clinical use of AIs in adult males. Tan RBW, Guay AT, and Hellstrom WJG. Clinical use of aromatase inhibitors in adult males. Sex Med Rev 2014;2:79-90. Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Effect of Ventilation Strategies on Residential Ozone Levels

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

Walker, Iain S.; Sherman, Max H.

Elevated outdoor ozone levels are associated with adverse health effects. Because people spend the vast majority of their time indoors, reduction in indoor levels of ozone of outdoor origin would lower population exposures and might also lead to a reduction in ozone-associated adverse health effects. In most buildings, indoor ozone levels are diminished with respect to outdoor levels to an extent that depends on surface reactions and on the degree to which ozone penetrates the building envelope. Ozone enters buildings from outdoors together with the airflows that are driven by natural and mechanical means, including deliberate ventilation used to reducemore » concentrations of indoor-generated pollutants. When assessing the effect of deliberate ventilation on occupant health one should consider not only the positive effects on removing pollutants of indoor origin but also the possibility that enhanced ventilation might increase indoor levels of pollutants originating outdoors. This study considers how changes in residential ventilation that are designed to comply with ASHRAE Standard 62.2 might influence indoor levels of ozone. Simulation results show that the building envelope can contribute significantly to filtration of ozone. Consequently, the use of exhaust ventilation systems is predicted to produce lower indoor ozone concentrations than would occur with balanced ventilation systems operating at the same air-­exchange rate. We also investigated a strategy for reducing exposure to ozone that would deliberately reduce ventilation rates during times of high outdoor ozone concentration while still meeting daily average ventilation requirements.« less

Dichloroacetate treatment for mitochondrial cytopathy: long-term effects in MELAS.

PubMed

Mori, Masato; Yamagata, Takanori; Goto, Tamako; Saito, Shigeko; Momoi, Mariko Y

2004-10-01

The long-term effects of the sodium salt of dichloroacetic acid (DCA) were evaluated in four patients with mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes (MELAS) carrying A3243G mutation. Oral administration of DCA in MELAS patients was followed for an average of 5 years 4 months. Serum levels of lactate and pyruvate were maintained at around 10 and 0.6 mg/dl, respectively. Serum levels of DCA were 40-136 microg/ml. Symptoms responding to treatment included persistent headache, abdominal pain, muscle weakness, and stroke-like episodes. In contrast, no improvements in mental status, deafness, short stature, or neuroelectrophysiological findings were observed. Adverse effects included mild liver dysfunction in all patients, hypocalcemia in three and peripheral neuropathy in one. None of these adverse events was severe enough to require discontinuation of treatment. To determine suitable indications for DCA therapy, analysis of many more patients who have undergone DCA administration is required.

Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity.

PubMed

Baad-Hansen, L; Cairns, Be; Ernberg, M; Svensson, P

2010-01-01

We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.

Gabapentin for chronic neuropathic pain and fibromyalgia in adults

PubMed Central

Moore, R Andrew; Wiffen, Philip J; Derry, Sheena; McQuay, Henry J

2014-01-01

Background This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning. Objectives To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management. Search methods We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011. Selection criteria Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over. Data collection and analysis Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMM-PACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. Main results Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions. Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo. There were insufficient data for comparisons with other active treatments. Authors’ conclusions Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and participants available for analysis. PMID:21412914

Gabapentin for chronic neuropathic pain and fibromyalgia in adults.

PubMed

Moore, R Andrew; Wiffen, Philip J; Derry, Sheena; McQuay, Henry J

2011-03-16

This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning. To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management. We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011. Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over. Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMMPACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions.Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo.There were insufficient data for comparisons with other active treatments. Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and participants available for analysis.

During stress, heart rate variability moderates the impact of childhood adversity in women with breast cancer.

PubMed

Tell, Dina; Mathews, Herbert L; Burr, Robert L; Witek Janusek, Linda

2018-03-01

Childhood adversity has long-lasting neuro-biological effects that can manifest as exaggerated stress responsivity to environmental challenge. These manifestations include a dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis as well as increased levels of inflammatory mediators in response to stress. In this investigation, vagal parasympathetic activity was assessed for its capacity to moderate the relationship between childhood adversity and stress responsivity (cortisol and inflammation) during an acute laboratory challenge (Trier Social Stress Test-TSST). Thirty women recently diagnosed with breast cancer underwent the TSST during which their heart rate was recorded and saliva samples collected for measurement of cortisol and the proinflammatory cytokine, IL-6. Vagal activity during the TSST was calculated as the high-frequency (HF) component of heart rate variability (HRV). Vagal activity during the TSST moderated the effect of childhood adversity on both the cortisol and the IL-6 response. Women who had lower vagal stress-reactivity during the TSST and reported greater childhood adversity showed a larger rise in cortisol and IL-6 when compared to women with lower childhood adversity. The findings demonstrate that women with exposure to childhood adversity and low vagal stress-reactivity (reduced parasympathetic activity) exhibit an elevated stress response characterized by greater cortisol and proinflammatory cytokine release. Inflammatory burden and HPA dysregulation subsequent to stress may impair cancer control.

High-throughput screening of chemical effects on steroidogenesis using H295R human adrenocortical carcinoma cells

EPA Science Inventory

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2,060 chemical samples...

THE EFFECT OF PH, PHOSPHATE AND OXIDANT ON THE REMOVAL OF ARSENIC FROM DRINKING WATER DURING IRON REMOVAL

EPA Science Inventory

Arsenic is a naturally occurring drinking water contaminant that has known adverse human health effects. The recent compilation of new health effects data prompted the U.S. Environmental Protection Agency (USEPA) to reduce the previous arsenic maximum contaminant level (MCL) of ...

THE EFFECT OF PH, PHOSPHATE AND OXIDANT ON THE REMOVAL OF ARSENIC FROM DRINKING WATER DURING IRON REMOVAL

EPA Science Inventory

Arsenic is a naturally occurring drinking water contaminant that has known adverse human health effects. The recent compilation of new health effects data prompted the U.S. Environmental Protection Agency (USEPA) to recently reduce the previous arsenic maximum contaminant level ...

[Efficacy and safety of TS-1 monotherapy for advanced/metastatic breast cancer - an observational study by the Kumamoto Breast Cancer Cooperative Group(KBCCG)].

PubMed

Yamamoto, Yutaka; Nishimura, Reiki; Tanigawa, Tomio; Kawano, Ichiro; Hayashi, Kyoji; Kuramoto, Masafumi; Yamamoto-Ibusuki, Mutsuko; Iwase, Hirotaka

2014-10-01

TS-1, an oral fluoropyrimidine, is known to be effective for the treatment of various carcinomas including advanced/metastatic breast cancer.The Kumamoto Breast Cancer Cooperative Group(KBCCG)conducted an observational study, wherein, the efficacy and safety of TS-1 monotherapy was analyzed in 35 patients with recurrent or metastatic breast cancer.The median time to cancer progression was 3.7 months, overall response rate was 12%, and clinical benefit rate was 32%. Adverse events were observed in 27 patients(77%), and adverse events of Grade >3 were observed in 7 patients(20%). The rate of treatment-related Grade 3 and 4 adverse events increased, and was associated with poor levels of creatinine clearance(Ccr)ie <60mL/min.This study suggests that TS-1 monotherapy can potentially be used as a salvage treatment for advanced/metastatic breast cancer owing to its safety and efficacy.Measuring the level of Ccr before TS-1 therapy should be considered to avoid severe adverse events.

Cardiovascular adverse effects of phenytoin.

PubMed

Guldiken, B; Rémi, J; Noachtar, Soheyl

2016-05-01

Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses.

Effects of daily variation in outdoor particulates and ambient acid species in normal and asthmatic children

PubMed Central

Ward, D; Roberts, K; Jones, N; Harrison, R; Ayres, J; Hussain, S; Walters, S

2002-01-01

Background: Evidence suggests that the respiratory health of children may be adversely affected by daily variation in outdoor pollutants, particularly ozone and particulates. However, data from the UK are sparse and the contribution of different particulate fractions and acid species, together with the identification of those individuals most at risk, are not clear. Methods: One hundred and sixty two 9 year old children were enrolled from two inner city locations and recorded daily symptoms and twice daily peak expiratory flow (PEF) over 8 week periods in the winter and summer. Their results were analysed with daily pollutant levels at appropriate lags using regression models which corrected for trends, weather, pollen, and autocorrelation. Results: Pollutant levels were generally low, especially in the summer. Multiple statistically significant associations were noted between health outcomes and pollutant concentrations, but no consistent patterns in identified effects were apparent between pollutants, lags, direction of observed effect, or location. There was no evidence to suggest that subgroups with atopy or pre-existing wheeze are more sensitive to pollutant effects. Conclusion: These data do not suggest that adverse health outcomes are associated with daily variation in health effects. No evidence was found to indicate that particulates or individual acid and anion species are more closely related to adverse health outcomes than other pollutants. PMID:12037223

Study for Promotion of Health in Recycling Lead - Rationale and design.

PubMed

Hara, Azusa; Gu, Yu-Mei; Petit, Thibault; Liu, Yan-Ping; Jacobs, Lotte; Zhang, Zhen-Yu; Yang, Wen-Yi; Jin, Yu; Thijs, Lutgarde; Wei, Fang-Fei; Nawrot, Tim S; Staessen, Jan A

2015-06-01

The level at which low-level lead exposure produces subclinical adverse health effects in adults remains to be established. The Study for Promotion of Health in Recycling Lead (SPHERL) will enroll 500 newly hired workers, whose blood lead during 2 years of follow-up is expected to increase from levels less than 2 μg/dl, as currently observed in the US population, to 20-30 μg/dl. The main outcome variables to be studied are (i) blood pressure (BP) analyzed as a continuous or categorical variable, both cross-sectionally and longitudinally, and using conventional and ambulatory BP measurement; (ii) indexes of glomerular and tubular renal function, (iii) heart rate variability analyzed in the frequency domain as measure of autonomous sympathetic modulation, (iv) peripheral nerve conductivity velocity, (v) neurocognitive performance, and (vi) quality of life. Expected outcomes. Assuming a 10-fold increase in blood lead, SPHERL will have sufficient statistical power to detect over 2 years a steepening of the age-related rise in systolic BP from 1 to 5 mmHg and a doubling of the age-related decline in the estimated glomerular filtration rate from 3.5 to 7.0 ml/min/1.73 m(2). The longitudinal design of our study complies with the temporality principle of the Bradford-Hill criteria for assessing possible causality between outcomes and exposure. SPHERL will attempt to resolve the apparent contradiction between general population studies showing associations between adverse health effects and low lead exposure with blood lead levels below 5 μg/dl and studies conducted in occupational cohorts indicating that adverse effects of lead exposure occur at much higher blood lead levels.

GENE-ENVIRONMENT INTERACTIONS: A REVIEW OF EFFECTS ON REPRODUCTION AND DEVELOPMENT

EPA Science Inventory

Polymorphisms in genes can lead to differences in the level of susceptibility of individuals to potentially adverse effects of environmental influences, such as chemical exposure, on prenatal development or male or female reproductive function. We have reviewed the literature in ...

New therapy, new challenges: The effects of long-term continuous flow left ventricular assist device on inflammation.

PubMed

Grosman-Rimon, Liza; Billia, Filio; Fuks, Avi; Jacobs, Ira; A McDonald, Michael; Cherney, David Z; Rao, Vivek

2016-07-15

Surgically implanted continuous flow left ventricular assist devices (CF-LVADs) are currently used in patients with end-stage heart failure (HF). However, CF-LVAD therapy introduces a new set of complications and adverse events in these patients. Major adverse events with the CF-LVAD include right heart failure, vascular dysfunction, stroke, hepatic failure, and multi-organ failure, complications that may have inflammation as a common etiology. Our aim was to review the current evidence showing a relationship between these adverse events and elevated levels of inflammatory biomarkers in CF-LVAD recipients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dietary fats and health: dietary recommendations in the context of scientific evidence.

PubMed

Lawrence, Glen D

2013-05-01

Although early studies showed that saturated fat diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD), the evidence of dietary saturated fats increasing CAD or causing premature death was weak. Over the years, data revealed that dietary saturated fatty acids (SFAs) are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of saturated fats in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with saturated fats in the past are most likely due to factors other than SFAs, which are discussed here. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking.

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 establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.

A Comparison of the Effects of Three Intervention Approaches on Parental Self-Efficacy, Parenting Skills, and Parental Stress Levels of Impoverished Parents

ERIC Educational Resources Information Center

Rooney, MaryEllen

2012-01-01

The purpose of this study is to compare three intervention approaches that focused on alleviating some of the deleterious effects of poverty by building parental self-efficacy, increasing parenting skills, and decreasing parental stress levels in parents at-risk for negative child outcomes due to factors associated with adverse socioeconomic…

ADVERSE HEALTH EFFECTS FROM ENVIRONMENTAL MANGANESE EXPOSURE.

EPA Science Inventory

The ubiquitous element, manganese (Mn), is an essential nutrient, but toxic at excessive exposure levels. Therefore, the US EPA set guideline levels for Mn exposure through inhalation (reference concentration-RfC=0.05 ?g/m3) and ingestion (reference dose-RfD=0.14 mg/kg/day (10 mg...

Maternal and fetal toxicity in developmental toxicology bioassays: Weight changes and their biological significance

EPA Science Inventory

Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines call for the inclusion of a dose level(s) that induces “overt maternal toxicity.” The possibility that general maternal toxicit...

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...

Do shrubs reduce the adverse effects of grazing on soil properties?

USGS Publications Warehouse

Eldridge, David J.; Beecham, Genevieve; Grace, James B.

2015-01-01

Increases in the density of woody plants are a global phenomenon in drylands, and large aggregations of shrubs, in particular, are regarded as being indicative of dysfunctional ecosystems. There is increasing evidence that overgrazing by livestock reduces ecosystem functions in shrublands, but that shrubs may buffer the negative effects of increasing grazing. We examined changes in water infiltration and nutrient concentrations in soils under shrubs and in their interspaces in shrublands in eastern Australia that varied in the intensity of livestock grazing. We used structural equation modelling to test whether shrubs might reduce the negative effects of overgrazing on infiltration and soil carbon and nitrogen (henceforth ‘soil nutrients’). Soils under shrubs and subject to low levels of grazing were more stable and had greater levels of soil nutrients. Shrubs had a direct positive effect on soil nutrients; but, grazing negatively affected nutrients by increasing soil bulk density. Structural equation modelling showed that shrubs had a direct positive effect on water flow under ponded conditions but also enhanced water flow, indirectly, through increased litter cover. Any positive effects of shrubs on water flow under low levels of grazing waned at high levels of grazing. Our results indicate that shrubs may reduce the adverse effects of grazing on soil properties. Specifically, shrubs could restrict access to livestock and therefore protect soils and plants beneath their canopies. Low levels of grazing are likely to ensure the retention of soil water and soil carbon and nitrogen in shrubland soils.

The Impact of Adverse Child and Adult Experiences on Recovery from Serious Mental Illness

PubMed Central

Stumbo, Scott P.; Yarborough, Bobbi Jo H.; Paulson, Robert I.; Green, Carla A.

2015-01-01

Objective To compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. Methods As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a two-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Results Child and adult exposures to adverse experiences were high, at 91% and 82% respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning, social functioning, and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Conclusions and Implications for Practice Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. PMID:26053533

Complementary and alternative exercise for fibromyalgia: a meta-analysis.

PubMed

Mist, Scott David; Firestone, Kari A; Jones, Kim Dupree

2013-01-01

Complementary and alternative medicine includes a number of exercise modalities, such as tai chi, qigong, yoga, and a variety of lesser-known movement therapies. A meta-analysis of the current literature was conducted estimating the effect size of the different modalities, study quality and bias, and adverse events. The level of research has been moderately weak to date, but most studies report a medium-to-high effect size in pain reduction. Given the lack of adverse events, there is little risk in recommending these modalities as a critical component in a multimodal treatment plan, which is often required for fibromyalgia management.

Area-level risk factors for adverse birth outcomes: trends in urban and rural settings

PubMed Central

2013-01-01

Background Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban–rural status. Methods Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Results Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991–2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Conclusions Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse birth outcomes elsewhere may not be reaching isolated rural areas. PMID:23759062

Serum tryptase level is a better predictor of systemic side effects than prostaglandin D2 metabolites during venom immunotherapy in children.

PubMed

Cichocka-Jarosz, E; Sanak, M; Szczeklik, A; Brzyski, P; Gielicz, A; Pietrzyk, J J

2011-01-01

We performed a prospective study to analyze mast cell mediators as predictors of systemic adverse reactions during rush venom-specific immunotherapy (VIT) in children. Nineteen children aged 5-17 years received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP, Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas chromatography mass spectrometry before and after the rush protocol. Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse reactions during VIT. Baseline serum tryptase was lowest in children who had a Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis of variance confirmed that, in children who developed systemic adverse reactions during VIT, serum tryptase was higher both before and after desensitization and increased significantly following the procedure. Analysis of PGD2 metabolites in the prediction of systemic adverse reactions during VIT was inadequate (sensitivity 67% and specificity 0.53%), whilst prediction based on serum tryptase was accurate. In children with severe systemic adverse reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should be a standard procedure. Children with Apis mellifera venom allergy and baseline tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup. Lower baseline values of plasma and urinary PGD2 metabolite concentration in patients with systemic adverse reaction during VIT suggest that prostaglandin catabolism is altered.

Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort study.

PubMed

Schuetz, Philipp; Friedli, Natalie; Grolimund, Eva; Kutz, Alexander; Haubitz, Sebastian; Christ-Crain, Mirjam; Thomann, Robert; Zimmerli, Werner; Hoess, Claus; Henzen, Christoph; Mueller, Beat

2014-02-01

Despite the condition's high prevalence, the influence of hyperglycaemia on clinical outcomes in non-critical-care inpatients with infections remains ill defined. In this study, we analysed associations of glucose levels at admission and during initial inpatient treatment with the inflammatory response and clinical outcome in community-acquired pneumonia (CAP) patients. This secondary observational analysis included 880 confirmed CAP patients. We used severity-adjusted multivariate regression models to investigate associations of initial and 96 h mean glucose levels with serially measured biomarker levels over 7 days (C-reactive protein [CRP], procalcitonin, white blood cell count [WBC], pro-adrenomedullin [ProADM]) and adverse clinical course (death and intensive-care unit admission). In the 724 non-diabetic patients (82.3% of the study population), moderate or severe hyperglycaemia (glucose 6-11 mmol/l and >11 mmol/l, respectively) was associated with increased risk for adverse clinical course (adjusted OR [95% CI] 1.4 [0.8, 2.4] and 3.0 [1.1, 8.0], respectively) and with higher CRP, WBC and ProADM levels over 7 days (p < 0.05, ANOVA, all days). In diabetic patients (n = 156), no similar associations were found for initial hyperglycaemia, although mean 96 h glucose levels  ≥ 9 mmol/l were associated with adverse clinical course (adjusted OR 5.4 [1.1, 25.8]; p = 0.03). No effect modification by insulin treatment was detected (interaction terms p > 0.2 for all analyses). Initial hyperglycaemia in non-diabetic CAP patients, and prolonged hyperglycaemia in diabetic or non-diabetic CAP patients, are associated with a more pronounced inflammatory response and CAP-related adverse clinical outcome. Optimal glucose targets for insulin treatment of hyperglycaemia in non-critical-care settings should be defined.

Effect of intra-pregnancy nonsurgical periodontal therapy on inflammatory biomarkers and adverse pregnancy outcomes: a systematic review with meta-analysis.

PubMed

da Silva, Helbert Eustáquio Cardoso; Stefani, Cristine Miron; de Santos Melo, Nilce; de Almeida de Lima, Adriano; Rösing, Cassiano Kuchenbecker; Porporatti, André Luís; Canto, Graziela De Luca

2017-10-10

The aim of this systematic review with meta-analysis was to analyze the effects of intra-pregnancy nonsurgical periodontal therapy on periodontal inflammatory biomarkers and adverse pregnancy outcomes. On June 5, 2017, we searched PubMed, Cochrane, SCOPUS, Web of Science, LILACS, ProQuest, Open Grey, and Google Scholar databases. Randomized clinical trials in which pregnant women with chronic periodontitis underwent nonsurgical periodontal therapy, compared with an untreated group, tested for inflammatory biomarkers, and followed till delivery were included. Primary outcomes were preterm birth, low birth weight, and preeclampsia. Meta-analysis was performed with 5.3.5 version of Review Manager software. We found 565 references in the databases, 326 after duplicates removal, 28 met criteria for full text reading, and 4 met eligibility criteria for quantitative and qualitative synthesis. Intra-pregnancy nonsurgical periodontal therapy improved periodontal clinical parameters (periodontal pocket depth, clinical attachment level, and bleeding on probing) and reduced biomarker level from gingival crevicular fluid (GCF), and some from blood serum; however, it did not influence biomarker level from umbilical cord blood. Meta-analysis showed tendency for reduction of the risk of preterm birth before 37 weeks for treated group (risk ratio (RR) = 0.54, 95% CI 0.38-0.77; p = 0.0007; inconsistency indexes (I2) 32%) but did not show any difference for low birth weight occurrence (RR = 0.78, 95%CI 0.50-1.21; p = 0.27; I2 41%). No included study considered preeclampsia as a gestational outcome. These results demonstrated that the intra-pregnancy nonsurgical periodontal therapy decreased periodontal inflammatory biomarker levels from gingival crevicular fluid and some from serum blood, with no influence on inflammatory biomarker level from cord blood, and it did not consistently reduce adverse gestational adverse outcome occurrence. PROSPERO CRD42015027750.

Adversity and psychosis: a 10-year prospective study investigating synergism between early and recent adversity in psychosis.

PubMed

Lataster, J; Myin-Germeys, I; Lieb, R; Wittchen, H-U; van Os, J

2012-05-01

Recent studies have suggested that early adverse events, such as childhood trauma, may promote enduring liability for psychosis whereas more recent adverse events may act as precipitants. Examination of these environmental dynamics, however, requires prospective studies in large samples. This study examines whether the association between recent adverse events and psychosis is moderated by exposure to early adversity. A random regional representative population sample of 3021 adolescents and young adults in Munich, Germany, was assessed three times over a period of up to 10 years, collecting information on sociodemographic factors, environmental exposures, and measures of psychopathology and associated clinical relevance. Evidence of statistical non-additivity between early adversity (two levels) and more recent adversity (four levels) was assessed in models of psychotic symptoms. Analyses were a priori corrected for age, gender, cannabis use, and urbanicity. Early and recent adversity were associated with each other (RR = 1.32, 95% CI 1.06-1.66; P = 0.014) and displayed statistical non-additivity at the highest level of exposure to recent adversity (χ(2) = 4.59; P = 0.032). The findings suggest that early adversity may impact on later expression of psychosis either by increasing exposure to later adversity and/or by rendering individuals more sensitive to later adversity if it is severe. © 2011 John Wiley & Sons A/S.

Tailoring health-related messages for young adults with adverse childhood experiences (ACEs).

PubMed

Karatekin, Canan; Ahluwalia, Rohini; Desir, Michelle

2018-06-01

The goal was to identify factors that might affect likelihood of seeking health-related interventions for young adults with adverse childhood experiences (ACEs). We tested whether ACEs were associated with (1) regulatory focus (tendency toward promoting good outcomes versus preventing bad outcomes), and (2) patient activation (the intention to take active charge of one's health). We further tested whether promotion and prevention and patient activation were associated with each other and with health. Students at a public university (N = 321) completed online questionnaires assessing ACEs, regulatory focus, patient activation, and health. Greater childhood adversity showed small but significant associations with being a less activated patient and being less focused on promoting good outcomes. In contrast, greater childhood adversity had a much stronger association with focusing on preventing negative outcomes. Students with a more significant mental health history were more likely to have been exposed to childhood adversity, to be less activated patients, and to focus more on prevention. Results suggest that using a prevention focus may be effective in health messages aimed to reach individuals with high levels of ACEs. Furthermore, individuals with high levels of ACEs may benefit from interventions aimed at increasing patient activation. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Mediating and Moderating Effects of Workplace Social Capital on the Associations between Adverse Work Characteristics and Psychological Distress among Japanese Workers

PubMed Central

OSHIO, Takashi; INOUE, Akiomi; TSUTSUMI, Akizumi

2014-01-01

Our current study investigated how workplace social capital (WSC) mediates and moderates the associations between adverse work characteristics and psychological distress among Japanese workers. We collected cross-sectional data (N=9,350) from a baseline survey of an occupational Japanese cohort study. We focused on individual WSC and considered job demands/control, effort/reward, and two types (i.e., procedural and interactional) of organizational justice as work-characteristic variables. We defined psychological distress as a score of ≥5 on the Kessler Psychological Distress Scale (K6 scale). Multivariate logistic regression analyses predicted a binary variable of psychological distress by individual WSC and adverse work characteristics, adjusting for individual-level covariates. Individual WSC mediated the associations between adverse work characteristics and psychological distress in almost all model specifications. Additionally, individual WSC moderated the associations of psychological distress with high job demands, high effort, and low interactional justice when we used a high WSC cutoff point. In contrast, individual WSC did not moderate such interactions with low job control, reward, or procedural justice. We concluded that individual WSC mediated the associations between adverse work characteristics and psychological distress among Japanese workers while selectively moderating their associations at high levels of WSC. PMID:24705803

Future Water-Supply Scenarios, Cape May County, New Jersey, 2003-2050

USGS Publications Warehouse

Lacombe, Pierre J.; Carleton, Glen B.; Pope, Daryll A.; Rice, Donald E.

2009-01-01

Stewards of the water supply in New Jersey are interested in developing a plan to supply potable and non-potable water to residents and businesses of Cape May County until at least 2050. The ideal plan would meet projected demands and minimize adverse effects on currently used sources of potable, non-potable, and ecological water supplies. This report documents past and projected potable, non-potable, and ecological water-supply demands. Past and ongoing adverse effects to production and domestic wells caused by withdrawals include saltwater intrusion and water-level declines in the freshwater aquifers. Adverse effects on the ecological water supplies caused by groundwater withdrawals include premature drying of seasonal wetlands, delayed recovery of water levels in the water-table aquifer, and reduced streamflow. To predict the effects of future actions on the water supplies, three baseline and six future scenarios were created and simulated. Baseline Scenarios 1, 2, and 3 represent withdrawals using existing wells projected until 2050. Baseline Scenario 1 represents average 1998-2003 withdrawals, and Scenario 2 represents New Jersey Department of Environmental Protection (NJDEP) full allocation withdrawals. These withdrawals do not meet projected future water demands. Baseline Scenario 3 represents the estimated full build-out water demands. Results of simulations of the three baseline scenarios indicate that saltwater would intrude into the Cohansey aquifer as much as 7,100 feet (ft) to adversely affect production wells used by Lower Township and the Wildwoods, as well as some other near-shore domestic wells; water-level altitudes in the Atlantic City 800-foot sand would decline to -156 ft; base flow in streams would be depleted by 0 to 26 percent; and water levels in the water-table aquifer would decline as much as 0.7ft. [Specific water-level altitudes, land-surface altitudes, and present sea level when used in this report are referenced to the North American Vertical Datum of 1988 (NAVD 88).] Future scenarios 4 to 9 represent withdrawals and the effects on the water supply while using estimated full build-out water demands. In most townships, existing wells would be used for withdrawals in the simulation. However, in Lower and Middle Townships, the Wildwoods, and the Cape Mays, withdrawals from some wells would be terminated, reduced, or increased. Depending on the scenario, proposed production wells would be installed in locations far from the saltwater fronts, in deep freshwater aquifers, in deeper saltwater aquifers, or proposed injection wells would be installed to inject reused water to create a freshwater barrier to saltwater intrusion. Simulations indicate that future Scenarios 4 to 9 would reduce many of the adverse effects of Scenarios 1, 2, and 3. No future scenario will minimize all adverse impacts. In Scenario 4, Lower Township would drill two production wells in the Cohansey aquifer farther from the Delaware shoreline than existing wells and reduce withdrawals from wells near the shoreline. Wildwood Water Utility (WWU) would reduce withdrawals from existing wells in the Cohansey aquifer and increase withdrawals from wells in the Rio Grande water-bearing zone. Results of the simulation indicate that saltwater intrusion and ecological-water supply problems would be reduced but not as much as in Scenarios 5, 7, 8, and 9. In Scenario 5, the Wildwoods and Lower Township each would install a desalination plant and drill two wells to withdraw saltwater from the Atlantic City 800-foot sand. Saltwater intrusion problems would be reduced to the greatest extent with this scenario. Ecological water supplies remain constant or decline from 2003 baseline values. Water-level altitudes would decline to -193 ft in the Atlantic City 800-foot sand, the deepest potentiometric level for all scenarios. In Scenario 6, Lower Township would build a tertiary treatment system and drill three wells open to the Cohanse

A Case control study of cardiovascular disease and arsenic exposure in Inner Mongolia, China

EPA Science Inventory

Background: Millions of people are at risk from the adverse effects of waterborne arsenic. Although the cardiovascular effects of high exposures to arsenic have been well documented, few individual level prospective studies have assessed cardiovascular risk at moderate exposures....

A health risk benchmark for the neurologic effects of styrene: comparison with NOAEL/LOAEL approach.

PubMed

Rabovsky, J; Fowles, J; Hill, M D; Lewis, D C

2001-02-01

Benchmark dose (BMD) analysis was used to estimate an inhalation benchmark concentration for styrene neurotoxicity. Quantal data on neuropsychologic test results from styrene-exposed workers [Mutti et al. (1984). American Journal of Industrial Medicine, 5, 275-286] were used to quantify neurotoxicity, defined as the percent of tested workers who responded abnormally to > or = 1, > or = 2, or > or = 3 out of a battery of eight tests. Exposure was based on previously published results on mean urinary mandelic- and phenylglyoxylic acid levels in the workers, converted to air styrene levels (15, 44, 74, or 115 ppm). Nonstyrene-exposed workers from the same region served as a control group. Maximum-likelihood estimates (MLEs) and BMDs at 5 and 10% response levels of the exposed population were obtained from log-normal analysis of the quantal data. The highest MLE was 9 ppm (BMD = 4 ppm) styrene and represents abnormal responses to > or = 3 tests by 10% of the exposed population. The most health-protective MLE was 2 ppm styrene (BMD = 0.3 ppm) and represents abnormal responses to > or = 1 test by 5% of the exposed population. A no observed adverse effect level/lowest observed adverse effect level (NOAEL/LOAEL) analysis of the same quantal data showed workers in all styrene exposure groups responded abnormally to > or = 1, > or = 2, or > or = 3 tests, compared to controls, and the LOAEL was 15 ppm. A comparison of the BMD and NOAEL/LOAEL analyses suggests that at air styrene levels below the LOAEL, a segment of the worker population may be adversely affected. The benchmark approach will be useful for styrene noncancer risk assessment purposes by providing a more accurate estimate of potential risk that should, in turn, help to reduce the uncertainty that is a common problem in setting exposure levels.

Impact of Life History on Fear Memory and Extinction

PubMed Central

Remmes, Jasmin; Bodden, Carina; Richter, S. Helene; Lesting, Jörg; Sachser, Norbert; Pape, Hans-Christian; Seidenbecher, Thomas

2016-01-01

Behavioral profiles are strongly shaped by an individual's whole life experience. The accumulation of negative experiences over lifetime is thought to promote anxiety-like behavior in adulthood (“allostatic load hypothesis”). In contrast, the “mismatch hypothesis” of psychiatric disease suggests that high levels of anxiety-like behavior are the result of a discrepancy between early and late environment. The aim of the present study was to investigate how different life histories shape the expression of anxiety-like behavior and modulate fear memory. In addition, we aimed to clarify which of the two hypotheses can better explain the modulation of anxiety and fear. For this purpose, male mice grew up under either adverse or beneficial conditions during early phase of life. In adulthood they were further subdivided in groups that either matched or mismatched the condition experienced before, resulting in four different life histories. The main results were: (i) Early life benefit followed by late life adversity caused decreased levels of anxiety-like behavior. (ii) Accumulation of adversity throughout life history led to impaired fear extinction learning. Late life adversity as compared to late life benefit mainly affected extinction training, while early life adversity as compared to early life benefit interfered with extinction recall. Concerning anxiety-like behavior, the results do neither support the allostatic load nor the mismatch hypothesis, but rather indicate an anxiolytic effect of a mismatched early beneficial and later adverse life history. In contrast, fear memory was strongly affected by the accumulation of adverse experiences over the lifetime, therefore supporting allostatic load hypothesis. In summary, this study highlights that anxiety-like behavior and fear memory are differently affected by specific combinations of adverse or beneficial events experienced throughout life. PMID:27757077

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing

PubMed Central

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A.; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space. PMID:29545755

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing.

PubMed

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space.

Multiple lines of evidence risk assessment of American robins exposed to polychlorinated dibenzofurans (PCDFS) and polychlorinated dibenzo-P-dioxins (PCDDS) in the Tittabawassee River floodplain, Midland, Michigan, USA.

PubMed

Tazelaar, Dustin L; Fredricks, Timothy B; Seston, Rita M; Coefield, Sarah J; Bradley, Patrick W; Roark, Shaun A; Kay, Denise P; Newsted, John L; Giesy, John P; Bursian, Steven J; Zwiernik, Matthew J

2013-06-01

Concentrations of polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) in Tittabawassee River floodplain soils and biota downstream of Midland, Michigan, USA, are greater than regional background concentrations. From 2005 to 2008, a multiple lines of evidence approach was utilized to evaluate the potential for effects of PCDD/DFs on American robins (Turdus migratorius) breeding in the floodplains. A dietary-based assessment indicated there was potential for adverse effects for American robins predicted to have the greatest exposures. Conversely, a tissue-based risk assessment based on site-specific PCDD/DF concentrations in American robin eggs indicated minimal potential for adverse effects. An assessment based on reproductive endpoints indicated that measures of hatch success in study areas were significantly less than those of reference areas. However, there was no dose-response relationship between that endpoint and concentrations of PCDD/DF. Although dietary-based exposure and reproductive endpoint assessments predicted potential for adverse effects to resident American robins, the tissue-based assessment indicates minimal to no potential for adverse effects, which is reinforced by the fact the response was not dose related. It is likely that the dietary assessment is overly conservative given the inherent uncertainties of estimating dietary exposure relative to direct tissue-based assessment measures. Based on the available data, it can be concluded that exposure to PCDD/DFs in the Tittabawassee River floodplain would not likely result in adverse population-level effects to American robins. Copyright © 2013 SETAC.

Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease.

PubMed

Xu, San-Qing; Li, Xu-Fang; Zhu, Hui-Yun; Liu, Yan; Fang, Feng; Chen, Ling

2013-10-01

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.

The effect of an adverse psychological environment on salivary cortisol levels in the elderly differs by 5-HTTLPR genotype.

PubMed

Ancelin, Marie-Laure; Scali, Jacqueline; Norton, Joanna; Ritchie, Karen; Dupuy, Anne-Marie; Chaudieu, Isabelle; Ryan, Joanne

2017-12-01

An adverse psychological environment (e.g. stressful events or depression) has been shown to influence basal cortisol levels and cortisol response to stress. This differs depending on the adverse stimuli, but also varies across individuals and may be influenced by genetic predisposition. An insertion/deletion polymorphism in the serotonin transporter gene ( 5-HTTLPR ) is a strong candidate in this regard. To investigate how stressful life events and depression are associated with diurnal cortisol levels in community-dwelling elderly and determine whether this varies according to genetic variability in the 5-HTTLPR . This population-based study included 334 subjects aged 65 and older (mean (SD) = 76.5 (6.3)). Diurnal cortisol was measured on two separate days, under quiet (basal) and stressful conditions. The number of recent major stressful events experienced during the past year was assessed from a 12-item validated questionnaire as an index of cumulative recent stressful events. Lifetime trauma was evaluated using the validated Watson's PTSD inventory, which evaluates the most severe traumatic or frightening experience according to DSM criteria. Depression was defined as having a Mini-International Neuropsychiatric Interview (MINI) diagnosis of current major depressive disorder or high levels of depressive symptoms (Center for Epidemiologic Studies-Depression Scale ≥16). 5-HTTLPR genotyping was performed on blood samples. Exposure to stressful life events was associated with lower basal evening cortisol levels overall, and in the participants with the 5-HTTLPR L allele but not the SS genotype. The greatest effects (over 50% decrease, p < 0.001) were observed for the LL participants having experienced multiple recent stressful events or severe lifetime traumas. Participants with the L allele also had higher evening cortisol stress response. Conversely, depression tended to be associated with a 42% higher basal morning cortisol in the SS participants specifically, but did not modify the association between stressful events and cortisol levels. An adverse psychological environment is associated with basal cortisol levels and cortisol stress response, but this differs according to 5-HTTLPR genotype.

Minimizing adverse events while maintaining clinical improvement in a pediatric attention-deficit/hyperactivity disorder crossover trial with dextroamphetamine and methylphenidate.

PubMed

Ramtvedt, Bjørn E; Aabech, Henning S; Sundet, Kjetil

2014-04-01

The purpose of this study was to investigate whether the availability of both dextroamphetamine and methylphenidate provides an opportunity to minimize adverse events in a pediatric attention-deficit/hyperactivity disorder (ADHD) stimulant trial. Thirty-six medication-naïve children 9-14 years of age, diagnosed with ADHD, were enrolled for 6 weeks in a crossover trial, with 2 weeks of methylphenidate, dextroamphetamine, and a placebo in a randomly assigned, counterbalanced sequence. Barkley's Side-Effect Rating Scale (SERS), rated by parents, was used to assess adverse events. SERS were available for 34 children, and data were analyzed both at the group and the single-subject level. The side-effect profiles of dextroamphetamine and methylphenidate appeared similar at the group level. Overall, insomnia and decreased appetite were the only adverse events associated with the stimulants as compared with placebo. No significant increase from placebo to stimulant conditions was detected on SERS items reflecting emotional symptoms. Furthermore, dextroamphetamine and methylphenidate did not differ from each other on any SERS item, except that dextroamphetamine was associated with higher severity of "insomnia" and a higher prevalence of "unusually happy." Single-subject analyses showed that one or more adverse events were reported in 14 children (41%), and were evenly distributed between those with dextroamphetamine as the drug that showed the greatest reduction in their ADHD symptoms ("best drug") and those with methylphenidate as their best drug. Among children in whom both stimulants were associated with a decrease in ADHD symptoms, a clinically valid difference between the two stimulants in total adverse events score was found in 7 (39%) of the 18 cases. In these children, the availability of both stimulants provided an opportunity to minimize adverse events, while maintaining a reduction in ADHD symptoms. The availability of both dextroamphetamine and methylphenidate may contribute to minimize adverse events in a subsample of children in pediatric ADHD stimulant trials. The study was first registered in clinical trials September 28, 2010. Clinical Trials.gov Identifier: NCT01220440.

Minimizing Adverse Events While Maintaining Clinical Improvement in a Pediatric Attention-Deficit/Hyperactivity Disorder Crossover Trial with Dextroamphetamine and Methylphenidate

PubMed Central

Aabech, Henning S.; Sundet, Kjetil

2014-01-01

Abstract Objective: The purpose of this study was to investigate whether the availability of both dextroamphetamine and methylphenidate provides an opportunity to minimize adverse events in a pediatric attention-deficit/hyperactivity disorder (ADHD) stimulant trial. Methods: Thirty-six medication-naïve children 9–14 years of age, diagnosed with ADHD, were enrolled for 6 weeks in a crossover trial, with 2 weeks of methylphenidate, dextroamphetamine, and a placebo in a randomly assigned, counterbalanced sequence. Barkley's Side-Effect Rating Scale (SERS), rated by parents, was used to assess adverse events. SERS were available for 34 children, and data were analyzed both at the group and the single-subject level. Results: The side-effect profiles of dextroamphetamine and methylphenidate appeared similar at the group level. Overall, insomnia and decreased appetite were the only adverse events associated with the stimulants as compared with placebo. No significant increase from placebo to stimulant conditions was detected on SERS items reflecting emotional symptoms. Furthermore, dextroamphetamine and methylphenidate did not differ from each other on any SERS item, except that dextroamphetamine was associated with higher severity of “insomnia” and a higher prevalence of “unusually happy.” Single-subject analyses showed that one or more adverse events were reported in 14 children (41%), and were evenly distributed between those with dextroamphetamine as the drug that showed the greatest reduction in their ADHD symptoms (“best drug”) and those with methylphenidate as their best drug. Among children in whom both stimulants were associated with a decrease in ADHD symptoms, a clinically valid difference between the two stimulants in total adverse events score was found in 7 (39%) of the 18 cases. In these children, the availability of both stimulants provided an opportunity to minimize adverse events, while maintaining a reduction in ADHD symptoms. Conclusions: The availability of both dextroamphetamine and methylphenidate may contribute to minimize adverse events in a subsample of children in pediatric ADHD stimulant trials. Clinical Trials Registry: The study was first registered in clinical trials September 28, 2010. Clinical Trials.gov Identifier: NCT01220440. PMID:24666268

The relationship between childhood adversity, recent stressors, and depression in college students attending a South African university.

PubMed

Mall, Sumaya; Mortier, Philippe; Taljaard, Lian; Roos, Janine; Stein, Dan J; Lochner, Christine

2018-03-09

College students are at risk of depression. This risk may be increased by the experience of childhood adversity and/or recent stressors. This study examined the association between reported experiences of childhood adversity, recent stressors and depression during the last 12 months in a cohort of South African university students. Six hundred and eighty-six first year students at Stellenbosch University in South Africa completed a health-focused e-survey that included items on childhood adversity, recent stressors and mood. Individual and population attributable risk proportions (PARP) between experiences of childhood adversity and 12-month stressful experiences and 12-month depression were estimated using multivariate binomial logistic regression analysis. About one in six students reported depression during the last 12 months. Being a victim of bullying and emotional abuse or emotional neglect during childhood were the strongest predictors of depression in the past year at both individual and population level. With regard to recent stressors, a romantic partner being unfaithful, serious ongoing arguments or break-ups with some other close friend or family member and a sexual or gender identity crisis were the strongest predictors of depression. The predictor effect of recent stressors was significantly reduced in the final model that adjusted for the type and number of childhood traumatic experiences. At a population level, academic stress, serious ongoing arguments or break-ups with a close friend or family member, and serious betrayal by someone close were the variables that yielded the highest PARP. Our findings suggest a significant relationship between early adversity, recent stressors, and depression here and throughout, consistent with the broader literature on predictors of depression. This study contributes to the limited data on college students' mental health in low and middle income countries including on the African continent. The findings provide information on the population level effect sizes of trauma as a risk factor for depression, as well as on the relationship between specific recent stressors and depression in college students.

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology.

PubMed

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study ( N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood ( p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant ( p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation.

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

PubMed Central

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant (p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation. PMID:28824498

An Integrative data mining approach to identifying Adverse Outcome Pathway (AOP) Signatures

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or populatio...

The androgen-deficient aging male: current treatment options.

PubMed

Tenover, J Lisa

2003-01-01

All delivery forms of testosterone should be equally efficacious in treating the androgen-deficient aging male if adequate serum testosterone levels are obtained. The testosterone preparations available in North America include the oral undecanoate, injectable testosterone esters, the scrotal patch, the nonscrotal transdermal patch, and the transdermal gels. Selection of a specific testosterone preparation for replacement therapy depends on many factors, including the magnitude and pattern of serum testosterone levels produced, side effects of the particular formulation, reversibility if an adverse event should occur, convenience of use, cosmetic issues related to the preparation, and cost. In addition, potential adverse effects of testosterone therapy applicable to all forms of testosterone delivery, such as fluid retention, gynecomastia, polycythemia, worsening of sleep apnea, change in cardiovascular-disease risk, or alterations in prostate health, need to be considered both prior to therapy and during treatment monitoring.

Neurophysiological symptoms and aspartame: What is the connection?

PubMed

Choudhary, Arbind Kumar; Lee, Yeong Yeh

2018-06-01

Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.

Effects of steaming on contaminants of emerging concern levels in seafood.

PubMed

Barbosa, Vera; Maulvault, Ana Luísa; Alves, Ricardo N; Kwadijk, Christian; Kotterman, Michiel; Tediosi, Alice; Fernández-Tejedor, Margarita; Sloth, Jens J; Granby, Kit; Rasmussen, Rie R; Robbens, Johan; De Witte, Bavo; Trabalón, Laura; Fernandes, José O; Cunha, Sara C; Marques, António

2018-05-19

Seafood consumption is a major route for human exposure to environmental contaminants of emerging concern (CeCs). However, toxicological information about the presence of CeCs in seafood is still insufficient, especially considering the effect of cooking procedures on contaminant levels. This study is one among a few who evaluated the effect of steaming on the levels of different CeCs (toxic elements, PFCs, PAHs, musk fragrances and UV-filters) in commercially relevant seafood in Europe, and estimate the potential risks associated with its consumption for consumers. In most cases, an increase in contaminant levels was observed after steaming, though varying according to contaminant and seafood species (e.g. iAs, perfluorobutanoate, dibenzo(ah)anthracene in Mytilus edulis, HHCB-Lactone in Solea sp., 2-Ethylhexyl salicylate in Lophius piscatorius). Furthermore, the increase in some CeCs, like Pb, MeHg, iAs, Cd and carcinogenic PAHs, in seafood after steaming reveals that adverse health effects can never be excluded, regardless contaminants concentration. However, the risk of adverse effects can vary. The drastic changes induced by steaming suggest that the effect of cooking should be integrated in food risk assessment, as well as accounted in CeCs regulations and recommendations issued by food safety authorities, in order to avoid over/underestimation of risks for consumer health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early Life Adversity Is Associated With Elevated Levels of Circulating Leptin, Irisin, and Decreased Levels of Adiponectin in Midlife Adults

PubMed Central

Joung, Kyoung Eun; Park, Kyung-Hee; Zaichenko, Lesya; Sahin-Efe, Ayse; Thakkar, Bindiya; Brinkoetter, Mary; Usher, Nicole; Warner, Dorothy; Davis, Cynthia R.; Crowell, Judith A.

2014-01-01

Context: Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known. Objectives: The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP). Design/Subjects/Setting: This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP. Results: Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity. Conclusion: Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity. PMID:24650014

Current Practices of Antiseptic Use in Canadian Neonatal Intensive Care Units.

PubMed

McCord, Helen; Fieldhouse, Elise; El-Naggar, Walid

2018-06-26

 This article assesses the degree of variability in the current practice of skin antiseptics used in Canadian neonatal intensive care units (NICUs) and different experiences related to each antiseptic used.  An anonymous survey was distributed to a clinical representative of each of the 124 Canadian level II and level III NICUs.  One hundred and two respondents (82.2%), representing all Canadian provinces, completed the survey. Chlorhexidine gluconate with/without alcohol was the antiseptic most used (96%) and the antiseptic with the highest reported adverse effects (68% reported skin burns/breakdown). Other antiseptics used include povidone-iodine (35%) and isopropyl alcohol (22%). Specific guidelines for antiseptic use were available in only 50% of the units with many NICUs lacking gestational and/or chronological age restrictions. Only 23% of responders believed that there was awareness among health care providers of the adverse effects of antiseptics used. Less than half (43%) were completely satisfied with the antiseptics used in their units.  Chlorhexidine gluconate is the most commonly used antiseptic in Canadian NICUs. The high number of associated adverse effects and the lack of guidelines regulating antiseptic use are of concern. Large clinical trials are urgently needed to guide practice and improve the safety of antiseptics. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Shared Pathoetiological Effects of Particulate Air Pollution and the Social Environment on Fetal-Placental Development

PubMed Central

2014-01-01

Exposure to particulate air pollution and socioeconomic risk factors are shown to be independently associated with adverse pregnancy outcomes; however, their confounding relationship is an epidemiological challenge that requires understanding of their shared etiologic pathways affecting fetal-placental development. The purpose of this paper is to explore the etiological mechanisms associated with exposure to particulate air pollution in contributing to adverse pregnancy outcomes and how these mechanisms intersect with those related to socioeconomic status. Here we review the role of oxidative stress, inflammation and endocrine modification in the pathoetiology of deficient deep placentation and detail how the physical and social environments can act alone and collectively to mediate the established pathology linked to a spectrum of adverse pregnancy outcomes. We review the experimental and epidemiological literature showing that diet/nutrition, smoking, and psychosocial stress share similar pathways with that of particulate air pollution exposure to potentially exasperate the negative effects of either insult alone. Therefore, socially patterned risk factors often treated as nuisance parameters should be explored as potential effect modifiers that may operate at multiple levels of social geography. The degree to which deleterious exposures can be ameliorated or exacerbated via community-level social and environmental characteristics needs further exploration. PMID:25574176

76 FR 29031 - National Emissions Standards for Hazardous Air Pollutants: Secondary Lead Smelting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... information collection provisions are best assured of having full effect if the Office of Management and... NOAEL no observed adverse effects level NRC National Research Council NTTAA National Technology Transfer... EPA's interpretation of this standard in effect at the time of the Clean Air Act amendments. Id. This...

Development of acute exposure guideline levels for airborne exposures to hazardous substances.

PubMed

Krewski, Daniel; Bakshi, Kulbir; Garrett, Roger; Falke, Ernest; Rusch, George; Gaylor, David

2004-04-01

Hazardous substances can be released into the atmosphere due to industrial and transportation accidents, fires, tornadoes, earthquakes, and terrorists, thereby exposing workers and the nearby public to potential adverse health effects. Various enforceable guidelines have been set by regulatory agencies for worker and ambient air quality. However, these exposure levels generally are not applicable to rare lifetime acute exposures, which possibly could occur at high concentrations. Acute exposure guideline levels (AEGLs) provide estimates of concentrations for airborne exposures for an array of short durations that possibly could cause mild (AEGL-1), severe, irreversible, potentially disabling adverse health effects (AEGL-2), or life threatening effects (AEGL-3). These levels can be useful for emergency responders and planners in reducing or eliminating potential risks to the public. Procedures and methodologies for deriving AEGLs are reviewed in this paper that have been developed in the United States, with direct input from international representatives of OECD member-countries, by the National Advisory Committee for Acute Exposure Guidelines for Hazardous Substances and reviewed by the National Research Council. Techniques are discussed for the extrapolation of effects across different exposure durations. AEGLs provide a viable approach for assisting in the prevention, planning, and response to acute airborne exposures to toxic agents.

Effects of Dietary Cadmium and Boron Supplementation on Performance, Eggshell Quality and Mineral Concentrations of Bone in Laying Hens.

PubMed

Olgun, Osman; Bahtiyarca, Yilmaz

2015-09-01

This study was conducted to determine the effects of supplementation of different levels of cadmium and boron on performance, eggshell quality, and mineral concentrations of bone in layer diets. In this trial, a total of 144 layer chickens, 21 weeks old, were randomly divided into 12 experimental groups. In each experimental group, there were four replicates, and in each of the replicates, there were three hens. Experimental diets consisted of all possible combinations of four levels of added cadmium (0, 5, 15, and 45 mg/kg) and three levels of added boron (0, 60, and 120 mg/kg) to the basal diet. Added cadmium (15 or 45 mg/kg) had a significant adverse effect on performance parameters (P < 0.01). Eggshell thickness increased with the addition of 5 mg/kg level of cadmium to the diet (P < 0.01). Tibia cadmium content increased with the addition of cadmium and boron in the diet (P < 0.01). However, tibia boron content decreased with the supplementation of cadmium (P < 0.01). These results indicate that the addition of boron to the diet did not prevent adverse effect of cadmium on performance and eggshell quality, or accumulation of cadmium in bone.

Managing respiratory effects of air pollution.

PubMed

Watson, Bianca K; Sheppeard, Vicky

2005-12-01

Exposure to air pollution (both indoor and outdoor) has many potential adverse effects on human health. This article looks at the adverse respiratory health effects of air pollution and gives some guidance about management of exposure in susceptible individuals. Motor vehicle and industrial emissions are the primary contributors to outdoor air pollution in Australia. High levels of ozone and other pollutants can cause respiratory symptoms in susceptible individuals. Air quality advisory systems exist in most states. Clinicians can incorporate the health effects of air pollution, and awareness of advisory systems in the education of their susceptible patients and their carers. Asthma and chronic airways disease management plans should include provision for possible exposure to high pollution events and steps that can be taken to reduce exposure.

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

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

PubMed

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

2014-01-01

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. To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. 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. 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. 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.

Risk assessment of human health from exposure to the discharged ballast water after full-scale electrolysis treatment.

PubMed

Zhang, Nahui; Wang, Yidan; Xue, Junzeng; Yuan, Lin; Wang, Qiong; Liu, Liang; Wu, Huixian; Hu, Kefeng

2016-06-01

The presence of disinfection by-products (DBPs) releasing from ballast water management systems (BWMS) can cause a possible adverse effects on humans. The objectives of this study were to compute the Derived No Effect Levels (DNELs) for different exposure scenarios and to compare these levels with the exposure levels from the measured DBPs in treated ballast water. The risk assessment showed that when using animal toxicity data, all the DNELs values were approximately 10(3)-10(12) times higher than the exposure levels of occupational and general public exposure scenarios, indicating the level of risk was low (risk characterization ratios (RCRs) < 1). However, when using human data, the RCRs were higher than 1 for dichlorobromomethane and trichloromethane, indicating that the risk of adverse effects on human were significant. This implies that there are apparent discrepancies between risk characterization from animal and human data, which may affect the overall results. We therefore recommend that when appropriate, human data should be used in risk assessment as much as possible, although human data are very limited. Moreover, more appropriate assessment factors can be considered to be employed in estimating the DNELs for human when the animal data is selected as the dose descriptors. Copyright © 2016 Elsevier Inc. All rights reserved.

ACUTE RESPIRATORY HEALTH EFFECTS OF AIR POLLUTION ON ASTHMATIC CHILDREN IN US INNER CITIES

EPA Science Inventory

BACKGROUND: Children with asthma in inner-city communities may be particularly vulnerable to adverse effects of air pollution because of their airways disease and exposure to relatively high levels of motor vehicle emissions. OBJECTIVE: To investigate the association between fluc...

Community Exposure to Air Manganese and Motor and Cognitive Outcomes

EPA Science Inventory

Although manganese (Mn) is an essential nutrient, occupational studies have shown inhaling high levels of Mn can lead to adverse nervous system health effects. Few studies have examined the health effects of air-Mn exposure on adults in a community. We conducted a cross-sectional...

EFFECT OF ATRAZINE ON IMPLANTATION AND EARLY PREGNANCY IN FOUR STRAINS OF RATS

EPA Science Inventory

Atrazine (ATR) is an herbicide that has been shown to have adverse reproductive effects including alterations in levels of pituitary hormones such as prolactin (prl) and luteinizing hormone (LH). Since prl's action to promote progesterone secretion is essential for the initiatio...

Effects of ToxCast Phase I Chemicals on Steroidogenesis in H295R Human Adrenocortical Carcinoma cells (SOT)

EPA Science Inventory

Steroid hormones are essential for proper development and reproduction. Disruption of steroidogenesis by environmental toxicants results in altered hormone levels causing adverse reproductive and developmental effects. H295R human adrenocortical carcinoma cells were used to evalu...

Complications of Moderate Sedation Versus Deep Sedation/General Anesthesia for Adolescent Patients Undergoing Third Molar Extraction.

PubMed

Inverso, Gino; Dodson, Thomas B; Gonzalez, Martin L; Chuang, Sung-Kiang

2016-03-01

To examine the complications resulting from moderate sedation versus deep sedation/general anesthesia for adolescent patients undergoing third molar extraction and determine whether any differences in complication risks exist between the 2 levels of sedation. We performed a prospective study of the Oral and Maxillofacial Surgery Outcomes System from January 2001 to December 2010. The primary predictor variable was the level of sedation, divided into 2 groups: moderate sedation versus deep sedation/general anesthesia. The primary outcome was the incidence of adverse complications resulting from the sedation level. Differences in the cohort characteristics were analyzed using the independent samples t test, χ(2) test, and analysis of variance, as appropriate. Multivariable logistic regression was used to measure the effect the level of sedation had on the adverse complication rate. Patients in the moderate sedation group had a complication rate of 0.5%, and patients in the deep sedation/general anesthesia group had a complication rate of 0.9%. Compared with moderate sedation, deep sedation/general anesthesia did not pose a significantly increased risk of adverse anesthesia complications (adjusted odds ratio 1.63, 95% confidence interval 0.95 to 2.81; P = .077). The results of our study have shown that the risk of adverse anesthesia complications is not increased when choosing between moderate and deep sedation/general anesthesia for adolescent patients undergoing third molar extraction. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Occupational exposure to anaesthetic gases: a role for TIVA.

PubMed

Irwin, Michael G; Trinh, Theresa; Yao, Che-Lin

2009-07-01

Modern anaesthesia is still mostly administered by the inhalational route and there is increasing concern over its potential for pollution. One of the first gaseous anaesthetic agents was nitrous oxide and this is still widely used today despite being associated with adverse effects caused by depression of vitamin B(12) function and diminished reproductive health. The use of halothane is associated with hepatitis but the adverse effects of newer halogenated hydrocarbons are less well recognised. Chronic exposure may cause reduction in antioxidant activity in plasma and erythrocytes, inhibition of neutrophil apoptosis, depression of central neuro-respiratory activity, increased DNA breaks, effects on cerebral blood circulation and altered renal function. Inhalational anaesthetics also have adverse environmental effects, including ozone damage and greenhouse gas effects. Levels of inhalational anaesthetics in the ambient air of operating theatres and recovery rooms often exceed those stated in national guidelines. Anaesthetic procedures can be modified and air-conditioning and air scavenging systems should be used to minimise the risks from occupational exposure and threats to the environment. Such contamination could be avoided with the use of total intravenous anaesthesia.

Investigating the associations among overtime work, health behaviors, and health: a longitudinal study among full-time employees.

PubMed

Taris, Toon W; Ybema, Jan Fekke; Beckers, Debby G J; Verheijden, Marieke W; Geurts, Sabine A E; Kompier, Michiel A J

2011-12-01

It has often been suggested that high levels of overtime lead to adverse health outcomes. One mechanism that may account for this association is that working overtime leads to elevated levels of stress, which could affect worker's behavioral decisions or habits (such as smoking and lack of physical activity). In turn, this could lead to adverse health. The present study examined this reasoning in a prospective longitudinal design. Data from the prospective 2-year Study on Health at Work (N = 649) were used to test our hypotheses. Structural equation analysis was used to examine the relationships among overtime, beneficial (exercising, intake of fruit and vegetables) and risky (smoking and drinking) health behaviors, and health indicators (BMI and subjective health). Working overtime was longitudinally related with adverse subjective health, but not with body mass. Moreover, working overtime was associated with lower levels of physical activity and intake of fruit and vegetables, but not with smoking and drinking. Finally, higher levels of risky and lower levels of beneficial health behaviors were longitudinally associated with ill health. The relation between overtime and ill health is partly accounted for by the unhealthy lifestyle in which overworkers tend to engage. However, a direct longitudinal effect of overtime on health suggested that the effects of overtime on health may also partly be due to the sustained physiological activation that results from working overtime. Whereas working a moderate amount of overtime does not usually entail major health risks, these will increase with increasing overtime.

Linking Adverse Outcome Pathways to Dynamic Energy Budgets: A Conceptual Model

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

Murphy, Cheryl; Nisbet, Roger; Antczak, Philipp

Ecological risk assessment quantifies the likelihood of undesirable impacts of stressors, primarily at high levels of biological organization. Data used to inform ecological risk assessments come primarily from tests on individual organisms or from suborganismal studies, indicating a disconnect between primary data and protection goals. We know how to relate individual responses to population dynamics using individual-based models, and there are emerging ideas on how to make connections to ecosystem services. However, there is no established methodology to connect effects seen at higher levels of biological organization with suborganismal dynamics, despite progress made in identifying Adverse Outcome Pathways (AOPs) thatmore » link molecular initiating events to ecologically relevant key events. This chapter is a product of a working group at the National Center for Mathematical and Biological Synthesis (NIMBioS) that assessed the feasibility of using dynamic energy budget (DEB) models of individual organisms as a “pivot” connecting suborganismal processes to higher level ecological processes. AOP models quantify explicit molecular, cellular or organ-level processes, but do not offer a route to linking sub-organismal damage to adverse effects on individual growth, reproduction, and survival, which can be propagated to the population level through individual-based models. DEB models describe these processes, but use abstract variables with undetermined connections to suborganismal biology. We propose linking DEB and quantitative AOP models by interpreting AOP key events as measures of damage-inducing processes in a DEB model. Here, we present a conceptual model for linking AOPs to DEB models and review existing modeling tools available for both AOP and DEB.« less

Critical appraisal of androgen use in hereditary angioedema: a systematic review.

PubMed

Riedl, Marc A

2015-04-01

To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE). PubMed was searched with no time limitations using the keywords hereditary angioedema or angio-oedema combined with danazol, stanozolol, and androgen. Qualifying articles were English-language reports of androgen use in patients with HAE, with relevant safety and/or efficacy information. Reports were categorized according to level of evidence (LOE). The search process identified 153 citations, 63 of which contained relevant information; 2 additional publications were identified while other citations were being reviewed. Fifteen LOE 2 studies and multiple LOE 4 reports provided efficacy data, confirming a high level of prophylactic efficacy for androgen therapy in HAE, with occasional reports of poor prophylactic response. Common adverse events include weight gain, menstrual irregularities, virilization, headaches, myalgias or cramps, mood changes, and elevations in creatine phosphokinase level, liver function test results, and serum lipid level. The risk of adverse events is often correlated with dose and/or treatment duration. Rare cases of hepatic adenomas and hepatocellular carcinoma associated with long-term androgen use often had no preceding changes in liver function test results. Androgen therapy may be effective for most patients with HAE; however, potential risks and adverse effects must be carefully considered and discussed with patients when considering options for long-term HAE prophylaxis. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

PubMed

Kim, Ha-Na; Kang, Sung-Goo; Roh, Yong Kyun; Choi, Min-Kyu; Song, Sang-Wook

2017-08-01

Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

TOXICITY STUDIES OF EPICHLOROHYDRIN IN SPRAGUE-DAWLEY RATS

EPA Science Inventory

Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, and 46 mg/kg-day, and for 90 days at dose levels of 1, 5, and 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but...

Effects of spray drift of glyphosate on nontarget terrestrial plants-A critical review.

PubMed

Cederlund, Harald

2017-11-01

Glyphosate is a widely used broad-spectrum postemergent herbicide used for weed control in both agricultural and nonagricultural settings. Spray drift of glyphosate can pose a risk to nontarget terrestrial plants and plant communities outside the intended area of application, but the lack of a well-established predicted-no-effect drift rate makes properly assessing such risk difficult. For this reason, a literature review and meta-analysis was carried out with the aim to determine the level of drift that is likely to cause harm to plants and to explore what spray-reducing targets would be sufficiently protective. No-observed-adverse effect rates, lowest-observed-adverse effect rates, and effect rates giving 10, 25, and 50% effects were extracted from a total of 39 different publications. The data were combined per species, and species sensitivity distributions were constructed and fitted with a log-logistic model to assess protectiveness. No systematic differences were detected between the responses of monocotyledons or dicotyledons, but wild plants were found to be generally less sensitive to glyphosate drift than domesticated plants. The results indicate that restricting spray drift to a level below 5 g a.e./ha would protect approximately 95% of all higher plant species against minor adverse effects of glyphosate drift and that rates below 1 to 2 g a.e./ha would be almost completely protective. No studies were encountered that evaluated effects of spray drift against nonvascular plants, and therefore, the conclusions are only valid for vascular plants. Environ Toxicol Chem 2017;36:2879-2886. © 2017 SETAC. © 2017 SETAC.

Meta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological Overview

PubMed Central

Golder, Su; Loke, Yoon K.; Bland, Martin

2011-01-01

Background There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies. Methods and Findings Searches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93–1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance. Conclusions Empirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors' Summary PMID:21559325

Introduction of risk size in the determination of uncertainty factor UFL in risk assessment

NASA Astrophysics Data System (ADS)

Xue, Jinling; Lu, Yun; Velasquez, Natalia; Yu, Ruozhen; Hu, Hongying; Liu, Zhengtao; Meng, Wei

2012-09-01

The methodology for using uncertainty factors in health risk assessment has been developed for several decades. A default value is usually applied for the uncertainty factor UFL, which is used to extrapolate from LOAEL (lowest observed adverse effect level) to NAEL (no adverse effect level). Here, we have developed a new method that establishes a linear relationship between UFL and the additional risk level at LOAEL based on the dose-response information, which represents a very important factor that should be carefully considered. This linear formula makes it possible to select UFL properly in the additional risk range from 5.3% to 16.2%. Also the results remind us that the default value 10 may not be conservative enough when the additional risk level at LOAEL exceeds 16.2%. Furthermore, this novel method not only provides a flexible UFL instead of the traditional default value, but also can ensure a conservative estimation of the UFL with fewer errors, and avoid the benchmark response selection involved in the benchmark dose method. These advantages can improve the estimation of the extrapolation starting point in the risk assessment.

Association of short-term exposure to ground-level ozone and respiratory outpatient clinic visits in a rural location – Sublette County, Wyoming, 2008–2011

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

Pride, Kerry R., E-mail: hgp3@cdc.gov; Wyoming Department of Health, 6101 Yellowstone Road, Suite 510, Cheyenne, WY 82002; Peel, Jennifer L.

Objective: Short-term exposure to ground-level ozone has been linked to adverse respiratory and other health effects; previous studies typically have focused on summer ground-level ozone in urban areas. During 2008–2011, Sublette County, Wyoming (population: ~10,000 persons), experienced periods of elevated ground-level ozone concentrations during the winter. This study sought to evaluate the association of daily ground-level ozone concentrations and health clinic visits for respiratory disease in this rural county. Methods: Clinic visits for respiratory disease were ascertained from electronic billing records of the two clinics in Sublette County for January 1, 2008–December 31, 2011. A time-stratified case-crossover design, adjusted formore » temperature and humidity, was used to investigate associations between ground-level ozone concentrations measured at one station and clinic visits for a respiratory health concern by using an unconstrained distributed lag of 0–3 days and single-day lags of 0 day, 1 day, 2 days, and 3 days. Results: The data set included 12,742 case-days and 43,285 selected control-days. The mean ground-level ozone observed was 47±8 ppb. The unconstrained distributed lag of 0–3 days was consistent with a null association (adjusted odds ratio [aOR]: 1.001; 95% confidence interval [CI]: 0.990–1.012); results for lags 0, 2, and 3 days were consistent with the null. However, the results for lag 1 were indicative of a positive association; for every 10-ppb increase in the 8-h maximum average ground-level ozone, a 3.0% increase in respiratory clinic visits the following day was observed (aOR: 1.031; 95% CI: 0.994–1.069). Season modified the adverse respiratory effects: ground-level ozone was significantly associated with respiratory clinic visits during the winter months. The patterns of results from all sensitivity analyzes were consistent with the a priori model. Conclusions: The results demonstrate an association of increasing ground-level ozone with an increase in clinic visits for adverse respiratory-related effects in the following day (lag day 1) in Sublette County; the magnitude was strongest during the winter months; this association during the winter months in a rural location warrants further investigation. - Highlights: • We assessed elevated ground-level ozone in frontier Sublette County, Wyoming. • Ground-level ozone concentrations were moderately to highly correlated between stations. • Adverse respiratory-related clinic visits occurred year round at lag 1. • Strongest association of clinic visits was in the coldest months at lag 1.« less

An elevated gap between admission and A1C-derived average glucose levels is associated with adverse outcomes in diabetic patients with pyogenic liver abscess.

PubMed

Liao, Wen-I; Sheu, Wayne Huey-Herng; Chang, Wei-Chou; Hsu, Chin-Wang; Chen, Yu-Long; Tsai, Shih-Hung

2013-01-01

To assess whether chronic glycemic control and stress-induced hyperglycemia, determined by the gap between admission glucose levels and A1C-derived average glucose (ADAG) levels adversely affects outcomes in diabetic patients with pyogenic liver abscess (PLA). Clinical, laboratory, and multi-detector computed tomography (MDCT) findings of 329 PLA patients (2004-2010) were retrospectively reviewed. HbA1C levels were used to determine long-term glycemic control status, which were then converted to estimated average glucose values. For the gap between admission glucose levels and ADAG levels, we used receiver operating characteristic (ROC) curve to determine the optimal cut-off values predicting adverse outcomes. Univariate and multivariate logistic regressions were used to identify predictors of adverse outcomes. Diabetic PLA patients with poorer glycemic control had significantly higher Klebsiella pneumoniae (KP) infection rates, lower albumin levels, and longer hospital stays than those with suboptimal and good glycemic control. The ROC curve showed that a glycemic gap of 72 mg/dL was the optimal cut-off value for predicting adverse outcomes and showed a 22.3% relative increase in adverse outcomes compared with a glycemic gap<72 mg/dL. Multivariate analysis revealed that an elevated glycemic gap≥72 mg/dL was important predictor of adverse outcomes. A glycemic gap≥72 mg/dL, rather than admission hyperglycemia or chronic glycemic control, was significantly correlated with adverse outcomes in diabetic PLA patients. Poorer chronic glycemic control in diabetic PLA patients is associated with high incidence of KP infection, hypoalbuminemia and longer hospital stay.

Early Socioeconomic Adversity and Young Adult Physical Illness: The Role of Body Mass Index and Depressive Symptoms

PubMed Central

Wickrama, K. A. S.; Kwon, Josephine A.; Oshri, Assaf; Lee, Tae Kyoung

2014-01-01

Purpose The present study investigated the psycho-physiological inter and intra-individual processes that mediate the linkage between childhood/adolescent socioeconomic adversities and adult health outcomes. Specifically, the proposed model examined the roles of youth depressive symptoms and BMI trajectories as mediators that explain the link between early adversity and young adults’ general health and physical illnesses after controlling for gender, race/ethnicity, and earlier general health reports. Methods Using a nationally representative sample of 12,424 from National Longitudinal Study of Adolescent Health (Add Health), this study used growth curve modeling to consider both the severity (initial level) as well as the change over time (deterioration or elevation) as psycho-physiological mediators, thereby acknowledging multiple facets of depressive symptoms and BMI trajectories as psych-physiological mediators of early adversity to adult health. Results Results provide evidence for (a) the influence of early childhood and early adolescent cumulative socioeconomic adversity on both the initial levels and changes over time of depressive symptoms and BMI and (b) the independent influences depressive symptoms and BMI trajectories on the general health and the physical illnesses of young adults Conclusions These findings contribute valuable knowledge to existing research by elucidating how early adversity exerts an enduring long-term influence on physical health problems in young adulthood; further, this information suggests effective intervention and prevention programs should incorporate multiple facets (severity and change over time) of multiple mechanisms (psychological and physiological). PMID:24856408

Proposed definition of environmental damage illustrated by the cases of genetically modified crops and invasive species.

PubMed

Bartz, Robert; Heink, Ulrich; Kowarik, Ingo

2010-06-01

The introduction of non-native plant species and the release of genetically modified (GM) crops can induce environmental changes at gene to ecosystem levels. Regulatory frameworks such as the Convention on Biological Diversity or the EU Deliberate Release Directive aim to prevent environmental damage but do not define the term. Although ecologists and conservationists often refer to environmental effects of GM crops or invasive species as damage, most authors do not disclose their normative assumptions or explain why some environmental impacts are regarded as detrimental and others are not. Thus far, a concise definition of environmental damage is missing and is necessary for a transparent assessment of environmental effects or risks. Therefore, we suggest defining environmental damage as a significant adverse effect on a biotic or abiotic conservation resource (i.e., a biotic or abiotic natural resource that is protected by conservational or environmental legislation) that has an impact on the value of the conservation resource, the conservation resource as an ecosystem component, or the sustainable use of the conservation resource. This definition relies on three normative assumptions: only concrete effects on a conservation resource can be damages; only adverse effects that lead to a decrease in the value of the conservation resource can be damages; and only significant adverse effects constitute damage to a conservation resource. Applying this definition within the framework of environmental risk assessment requires further normative determinations, for example, selection of a threshold to distinguish between adverse and significant adverse effects and approaches for assessing the environmental value of conservation resources. Such determinations, however, are not part of the definition of environmental damage. Rather they are part of the definition's operationalization through assessment procedures, which must be grounded in a comprehensible definition of environmental damage.

[Effects of excess pyridoxine-HCl on growth and urinary excretion of water-soluble vitamins in weaning rats].

PubMed

Fukuwatari, Tsutomu; Itoh, Keiko; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake level of pyridoxine-HCl in humans, we investigated the effects of excess pyridoxine-HCl administration on body weight gain, food intake, tissue weight, and urinary excretion of water-soluble vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0007% pyridoxine-HCl (control diet) or the same diet with 0.1%, 0.5%, 0.8% or 1.0% pyridoxine-HCl for 30 days. The body weight gain in the 0.8% and 1.0% groups, and the total food intake in the 1.0% group were significantly lower than those in the control group. The urinary excretion of pantothenic acid in the pyridoxine-HCl added groups were higher than that in the control group, while excessive pyridoxine-HCl intake did not affect the urinary excretion of other water-soluble vitamins. These results showed that the no-observed-adverse-effect-level (NOAEL) for pyridoxine-HCl was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and lowest-observed-adverse-effect-level (LOAEL) was 0.5% in diet, corresponding to 450 mg/kg body weight/day.

Adverse Health Effects Associated with Living in a Former Methamphetamine Drug Laboratory - Victoria, Australia, 2015.

PubMed

Wright, Jackie; Kenneally, Michaela E; Edwards, John W; Walker, G Stewart

2017-01-06

The manufacture of methamphetamine in clandestine drug laboratories occurs in various locations, including residential houses and apartments. Unlike the controlled manufacture of chemicals and drugs, clandestine manufacture results in the uncontrolled storage, use, generation, and disposal of a wide range of chemicals and the deposit of methamphetamine drug residues on indoor surfaces (1). These residues have been found at high levels on porous and nonporous surfaces and have been shown to persist for months to years (1). Persons exposed to these environments often have poorly defined exposures and health effects. It is commonly assumed that these levels of exposure are low compared with those related to illicit drug use or therapeutic use of amphetamine-based drugs for managing behavioral issues such as attention deficit hyperactivity disorder (2). In 2015, a family that was unknowingly exposed to methamphetamine residues in a house in Australia was found to have adverse health effects and elevated methamphetamine levels in hair samples, highlighting the potential for public health risks for persons who might live in methamphetamine-contaminated dwellings. This case study highlights the importance of the identification and effective decontamination of former clandestine drug laboratories.

Student profile with high adversity quotient in math learning

NASA Astrophysics Data System (ADS)

Hastuti, T. D.; Sari S, D. R.; Riyadi

2018-03-01

Lately a lot of research conducted to determine the effect of Adversity Quotient students on learning achievement. This is done because many students with excellent IQ and EQ, but often have problems when they are in the workforce. This study will analyze the profile of High School students with high Adversity Quotient (AQ) in learning mathematics. The test is done using a questionnaire to know the AQ level of the students, and the interview is done to get the data about the student profile. Based on the results of tests and interviews obtained data that students with high AQ able to face the learning of mathematics in various materials and with different models of learning.

Should I Be Concerned about Eating Fish and Shellfish?

MedlinePlus

... who are nursing risk exposing their children to contamination if they eat these fish. The EPA-FDA ... adverse health effects from contaminated fish even if contamination levels are low. Both of these groups are ...

Climate change science overview : asset management and adaptation to climate change

DOT National Transportation Integrated Search

2009-04-23

Impacts on transportation infrastructure: higher temperatures, more intense precipitation events, stronger storms and higher sea levels are likely to have adverse effects on transportation systems. Transportation contribution to greenhouse gas emissi...

Adverse Childhood Experiences and Higher-Level Functional Limitations Among Older Japanese People: Results From the JAGES Study.

PubMed

Amemiya, Airi; Fujiwara, Takeo; Murayama, Hiroshi; Tani, Yukako; Kondo, Katsunori

2018-01-16

A life-course perspective is essential in understanding the determinants of higher-level functional limitations. We examine the impact of adverse childhood experiences (ACEs) on higher-level functional limitations in older people. Data were from the Japan Gerontological Evaluation Study 2013, a population-based cohort of independent people aged 65 years or older across Japan (n = 19,220). ACEs before the age of 18 were assessed in terms of seven adversities: parental death, parental divorce, parental mental illness, family violence, physical abuse, psychological neglect, and psychological abuse. Associations between the cumulative number of ACEs and higher-level functional limitations were investigated by multivariate Poisson regression with robust error variances, adjusted for age, gender, childhood disadvantage, adult sociodemographics, adult health behaviors, and health status. Of the older people, 36.3% reported at least one ACE. Older people who had experienced two or more ACEs showed significantly greater higher-level functional limitations than those with no ACE in a crude model (prevalence ratio, PR = 1.61, 95% confidence interval, CI = 1.51-1.71). After adjusting the covariates, this association remained (PR = 1.19, 95% CI = 1.12-1.27). ACEs showed robust independent effects on higher-level functional limitations among older Japanese without disabilities, even after adjusting for potential covariates in childhood and adulthood. The current findings may help in understanding the impact of the latent effects of ACEs on functional limitations in older people. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dietary Fats and Health: Dietary Recommendations in the Context of Scientific Evidence1

PubMed Central

Lawrence, Glen D.

2013-01-01

Although early studies showed that saturated fat diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD), the evidence of dietary saturated fats increasing CAD or causing premature death was weak. Over the years, data revealed that dietary saturated fatty acids (SFAs) are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of saturated fats in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with saturated fats in the past are most likely due to factors other than SFAs, which are discussed here. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking. PMID:23674795

The impact of adverse child and adult experiences on recovery from serious mental illness.

PubMed

Stumbo, Scott P; Yarborough, Bobbi Jo H; Paulson, Robert I; Green, Carla A

2015-12-01

The purpose of this study was to compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a 2-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia, or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Child and adult exposures to adverse experiences were high, at 91% and 82%, respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning and social functioning and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. (c) 2015 APA, all rights reserved).

Immunotoxicity assessment for the novel Spleen tyrosine kinase inhibitor R406

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

Zhu Yanhong; Herlaar, Ellen; Masuda, Esteban S.

2007-06-15

Spleen tyrosine kinase (Syk) is a novel pharmaceutical target for treatment of allergic, autoimmune, and neoplastic disorders. Previous studies have indicated that Syk signaling plays critical roles in regulating the lymphohematopoietic system. These observations prompted us to investigate whether inhibition of Syk would promote immunotoxicity. In a series of studies, rats were treated orally with R406, at dose levels up to and including 100 mg/kg/day (or its prodrug R788 at dose levels up to and including 100 mg/kg/day, reduced to 50 mg/kg/day for females as MTD was exceeded), a potent Syk inhibitor, twice daily for 28 days. In addition tomore » standard toxicological assessments, immunophenotyping by flow cytometric analysis, and a study of humoral immune response measuring anti-KLH IgM and IgG levels, were undertaken. Other immunotoxicity studies included three host resistance models in female Balb/c mice to further ascertain effects of R406 on innate and acquired immunity. Following R406 treatment, expected immunomodulating effects (e.g., decreased thymic and spleen weight, hypocellularity of bone marrow, and reduced lymphocyte counts, including T and B cells) were observed in the rat studies. These changes essentially resolved during a 14-day treatment-free recovery period. A KLH challenge in rats demonstrated no adverse effects on IgG or IgM response. R788/406, administered orally at dose levels up to and including 80 mg/kg/day for 28 days, did not affect bacterial or viral clearance in the Listeria, Streptococcal, or Influenza host resistance mouse models, respectively. This correlated with previous in vitro macrophage and neutrophil function assays (assessing migration, phagocytosis, oxidative burst and microbicidal activity), which revealed that R406 did not adversely affect macrophage or neutrophil function in innate immune responses. Collectively, these results demonstrate that R406 has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect, suggesting that inhibition of Syk might not lead to unacceptable mechanism-based adverse effects.« less

Air quality in the Olona Valley and in vitro human health effects.

PubMed

Teoldi, Federico; Lodi, Marco; Benfenati, Emilio; Colombo, Andrea; Baderna, Diego

2017-02-01

Air quality is a major point in current health policies in force globally to protect human health and ecosystems. Cardiovascular and lung diseases are the pathologies most commonly associated with air pollution and it has been estimated that exposure to particulate matters and ground-level ozone and nitric oxides caused >500.000 premature deaths in Europe. Although air quality was generally improved in the recent years, further efforts are required to reduce the impact of air pollution on humans. The present study applied a multidisciplinary approach to estimate the adverse effects on the health of the inhabitants of the Olona Valley in the north of Italy. Chemical analyses quantified the air levels of metals, dioxins, PCBs, PAHs and some macropollutants, including total, fine and coarse airborne particles. These results were used as input for the health risk assessment and in vitro bioassays were used to evaluate possible adverse effects on the respiratory tract due to the organic pollutants adsorbed on the airborne particulate matter. Critical alerts were identified from the air characterization and from the chemical-based risk assessment in view of the levels of arsenic, nickel, benzene, fine and coarse particulate matters found in the investigated zone, which can induce severe adverse effects on human health. These findings were confirmed by bioassays with A549 and BEAS-2B cells. We also used the cell transformation assay with BALB/c 3T3 cells to assess the carcinogenicity of the organic extracts of collected particles as an innovative tool to establish the possible chronic effects of inhaled pollutants. No significant changes in morphological transformation were found suggesting that, although the extracts contain compounds with proven carcinogenic potential, in our experimental conditions the levels of these pollutants were too low to induce carcinogenesis as resulted also by the chemical-based risk assessment. Copyright © 2016 Elsevier B.V. All rights reserved.

A case of probable labetalol induced hyperkalaemia in pre-eclampsia.

PubMed

Thomas, Binny; Abdul Rouf, P V; El Kassem, Wessam; Al Hail, Moza; Stewart, Derek; Tharannum, Asma; Ahmed, Afif; Al Saadi, Muna

2014-12-01

Hyperkalemia can cause altered cardiac electrical conduction resulting in death. We describe a case of a 23-year old pregnant patient who presented with severe epigastric pain and vomiting. She was severely pre- eclamptic and received initial treatment with intravenous labetalol and decision was taken to deliver. She quickly became hyperkalaemic (serum potassium level 6.4 mmol/L) and labetalol was discontinued and intravenous hydralazine commenced. Post-surgery, her potassium levels were normal but due to rapidly rising blood pressure labetalol was recommenced, resulting in elevated potassium levels. Labetolol was discontinued, hydralazine prescribed, and potassium levels normalised. The adverse reaction was classified as 'probably' due to labetolol using the Naranjo Adverse Drug Reaction scale. This is the first reported case of labetolol induced hyperkalaemia in pregnancy, with life threatening consequences and hence all health professionals should be alert to this potential effect.

Efficacy of Nonsteroidal Anti-inflammatory Drug Prophylaxis for Heterotrophic Ossification in Hip Arthroscopy: A Systematic Review.

PubMed

Yeung, Marco; Jamshidi, Sahab; Horner, Nolan; Simunovic, Nicole; Karlsson, Jon; Ayeni, Olufemi R

2016-03-01

The purpose of this systematic review was to investigate the efficacy of nonsteroidal anti-inflammatory drug (NSAID) prophylaxis for preventing heterotopic ossification (HO) in the setting of hip arthroscopy. A systematic search was performed in duplicate for studies comparing the use of NSAID prophylaxis for HO in the setting of hip arthroscopy until March 2015. Study parameters--including sample size, incidence of HO, adverse effects, and level of symptoms--were obtained. Furthermore, the level of evidence of studies was collected and quality assessment was performed. The difference in incidence as well as pooled odds ratios were calculated and analyzed to compare no prophylaxis versus NSAID prophylaxis. This systematic review identified 5 studies, consisting of 1,662 patients, investigating NSAID prophylaxis in hip arthroscopy. HO was diagnosed with the use of postoperative hip radiographs at follow-up, with 95% of cases classified using the Brooker classification. The incidence of HO was 13.4% without NSAID prophylaxis and 3.3% with NSAID prophylaxis. Pooled odds ratios from the prospective studies were 0.07 (95% confidence interval [CI], 0.02 to 0.28; P = .0002; I(2) = 0%), showing with statistical significance that NSAID prophylaxis decreased the incidence of HO. The retrospective data similarly showed pooled odds ratios of 0.03 (95% CI, 0.00 to 1.43); P = .08; I(2) = 84%), although it was not statistically significant. Most of the patients who experienced HO in both groups were not reported to be symptomatic. Adverse effects and compliance were not consistently reported. The available orthopaedic literature suggests that the incidence of postoperative HO may be decreased with the use of NSAID prophylaxis in hip arthroscopy. However, the evidence is unclear regarding NSAID drug regimen choice, drug compliance, and adverse effects. Level III, systematic review of Level I, Level II, and Level III studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

A growth curve analysis of the course of dysthymic disorder: the effects of chronic stress and moderation by adverse parent-child relationships and family history.

PubMed

Dougherty, Lea R; Klein, Daniel N; Davila, Joanne

2004-12-01

Using mixed effects models, the authors examined the effects of chronic stress, adverse parent-child relationships, and family history on the 7.5-year course of dysthymic disorder. Participants included 97 outpatients with early-onset dysthymia who were assessed with semistructured interviews at baseline and 3 additional times at 30-month intervals for 7.5 years. Results indicated that higher levels of chronic stress 6 months prior to each follow-up predicted greater depression severity at follow-up, controlling for depression severity at the start of the chronic stress assessment. In addition, adverse parent-child relationships and family history of dysthymic disorder moderated this association. For patients with poorer parent-child relationships, chronic stress was associated with increased depression severity at follow-up, whereas patients with a higher familial loading for dysthymic disorder were less responsive to chronic stress over time. Copyright 2004 APA.

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs

PubMed Central

Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-01-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day. PMID:25874036

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs.

PubMed

Nam, Chunja; Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-03-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

HIV Protease Inhibitor Use During Pregnancy Is Associated With Decreased Progesterone Levels, Suggesting a Potential Mechanism Contributing to Fetal Growth Restriction

PubMed Central

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R.; Yudin, Mark H.; Murphy, Kellie E.; Walmsley, Sharon L.; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. PMID:25030058

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

PubMed

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R; Yudin, Mark H; Murphy, Kellie E; Walmsley, Sharon L; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Recommendation of an Occupational Exposure Level for Perfluro-N-Butyl Iodide

DTIC Science & Technology

2006-09-01

Clinical signs observed in some dogs, but not all dogs exposed to PFBI included salivation, limb and/or muscle tension, and non-specific signs of...Symposium 2003 considered, “…developmental deficits or delays, and goiter and other effects of frank hypothyroid condition to be adverse effects

ANTIOXIDANT SUPPLEMENTATION AND LUNG FUNCTIONS AMONG ASTHMATIC CHILDREN EXPOSED TO HIGH LEVELS OF AIR POLLUTANTS

EPA Science Inventory

Abstract

Air pollutant exposure has been related to adverse respiratory effects, in particular, in asthmatics. This effect could be the consequence of the oxidative stress caused by air pollutants on the lung. Antioxidant vitamins are free- radical scavengers, and could ha...

Application of ToxCast to evaluate potential biological effects from organic contaminants in Great Lakes tributaries

EPA Science Inventory

With the development of “high throughput” in-vitro biological assays, screening-level information on potential adverse biological effects is available for a rapidly increasing number of chemicals. The U.S. EPA ToxCast program has now evaluated several thousand chemica...

Acute ozone (O3) -induced impairment of glucose regulation: Age-related and temporal changes

EPA Science Inventory

O3 is associated with adverse cardiopulmonary health effects in humans and is thought to produce metabolic effects, such as insulin resistance. Recently, we showed that episodic O3 exposure increased insulin levels in aged rats. We hypothesized that O3 exposure could impair gluc...

Fact Sheets on Review of National Ambient Air Quality Standards for Ozone Staff Papers

EPA Pesticide Factsheets

The second draft Staff Paper points to an expanded body of health effects evidence suggesting a wide range of adverse health effects associated with exposure to ambient ozone. This is part of the process for review of the NAAQS for ground-level ozone.

Climate Change Impacts on Harmful Algal Blooms in U.S. Freshwaters: A Screening-Level Assessment

EPA Science Inventory

Cyanobacterial harmful algal blooms have serious adverse effects on human and environmental health. Herein, we develop a modeling framework that predicts the effect of climate change on cyanobacteria concentrations in reservoirs in the contiguous U.S. The framework, which uses cl...

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

Dourson, M.L.

The quantitative procedures associated with noncancer risk assessment include reference dose (RfD), benchmark dose, and severity modeling. The RfD, which is part of the EPA risk assessment guidelines, is an estimation of a level that is likely to be without any health risk to sensitive individuals. The RfD requires two major judgments: the first is choice of a critical effect(s) and its No Observed Adverse Effect Level (NOAEL); the second judgment is choice of an uncertainty factor. This paper discusses major assumptions and limitations of the RfD model.

Programmatic Life Cycle Environmental Assessment for Smoke/Obscurants. Volume 2. Red, White, and Plasticized White Phosphorus

DTIC Science & Technology

1983-07-01

data on toxic effects of unreacted P4 on soil systems are available. (3) Aquatic systems . Aquatic toxicity data on WP are presented in section IV.f...elevated phosphorus levels in aquatic systems will cause adverse effects . Phosphoric acids may lower water pH in systems with low water hardness. A pH...eutrophication of the system , will cause detrimental effects on the fish population. Fish kills can occur over the winter due to low oxygen levels. The

Application of the Beers Criteria to Alternate Level of Care Patients in Hospital Inpatient Units

PubMed Central

Slaney, Heather; MacAulay, Stacey; Irvine-Meek, Janice; Murray, Joshua

2015-01-01

Background: The Beers criteria were developed to help in identifying potentially inappropriate medications (PIMs) for elderly patients. These medications are often associated with adverse events and limited effectiveness in older adults. Patients awaiting an alternate level of care (ALC patients) are those who no longer require acute care hospital services and are waiting for placement elsewhere. They are often elderly, have complex medication regimens, and are at high risk of adverse events. At the time of this study no studies had applied the Beers criteria to ALC patients in Canadian hospitals. Objectives: To determine the proportion of ALC patients receiving PIMs and the proportion experiencing selected PIM-related adverse events. Methods: A retrospective chart review of ALC patients 65 years of age or older was performed to identify PIMs and the occurrence of selected adverse events (specifically central nervous system [CNS] events, falls, bradycardia, hypoglycemia, seizures, insomnia, gastrointestinal bleeding, and urinary tract infections). A logistic regression model with a random intercept for each patient was constructed to estimate odds ratios and probabilities of adverse events. Results: Fifty-two ALC patients were included in the study. Of these, 48 (92%) were taking a PIM. Of the 922 adverse events evaluated, 407 (44.1%) were associated with a regularly scheduled PIM. Among patients who were taking regularly scheduled PIMs, there was a significantly increased probability of an adverse CNS event and of a fall (p < 0.001 for both). The most common PIM medication classes were first-generation antihistamines (24 [46%] of the 52 patients), antipsychotics (21 patients [40%]), short-acting benzodiazepines (15 patients [29%]), and nonbenzodiazepine hypnotics (14 patients [27%]). Conclusions: A high proportion of ALC patients were taking PIMs and experienced an adverse event that may have been related to these drugs. These findings suggest that the ALC population might benefit from regular medication review and monitoring to prevent or detect adverse events. PMID:26157183

Childhood adversity and social functioning in psychosis: Exploring clinical and cognitive mediators.

PubMed

Palmier-Claus, Jasper; Berry, Katherine; Darrell-Berry, Hannah; Emsley, Richard; Parker, Sophie; Drake, Richard; Bucci, Sandra

2016-04-30

Childhood adversity may increase risk of impaired social functioning across the continuum of psychosis. However, the pathways by which adversity dictates functional outcome remain underexplored. This study investigated the association between childhood adversity and social functioning, and the clinical and cognitive mediators of this relationship. Fifty-four clinical (20 chronic, 20 first episode, 14 at ultra-high risk) and 120 non-clinical participants completed standardised questionnaires, semi-structured interviews and tests of theory of mind ability. The authors used multiple group structural equation modelling to fit mediation models allowing for differential relationships between the clinical and non-clinical samples. When examining each pathway separately, depression, paranoia and anxious attachment mediated the effect of childhood adversity on social functioning. In a combined model, depression was the only significant mediating variable with greater adversity predicting lower mood across groups. Childhood adversity did not significantly predict theory of mind ability in any of the models. This is the first study to indicate that childhood adversity acts on social functioning by increasing levels of depression, suggesting a common mechanism across the spectrum of psychosis. Clinical interventions should target low mood in order to improve social functioning at all stages of psychotic disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bitter melon (Momordica charantia): a review of efficacy and safety.

PubMed

Basch, Ethan; Gabardi, Steven; Ulbricht, Catherine

2003-02-15

The pharmacology, clinical efficacy, adverse effects, drug interactions, and place in therapy of bitter melon are described. Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter melon extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches. Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.

Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy.

PubMed

Kim, Dong Wook; Gu, Nami; Jang, In-Jin; Chu, Kon; Yu, Kyung-Sang; Cho, Joo-Youn; Yoon, Seo Hyun; Kim, Hwa Suk; Oh, Jeeyoung; Lee, Sang Kun

2012-01-01

The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Which daily experiences can foster well-being at work? A diary study on the interplay between flow experiences, affective commitment, and self-control demands.

PubMed

Rivkin, Wladislaw; Diestel, Stefan; Schmidt, Klaus-Helmut

2018-01-01

Previous research has provided strong evidence for affective commitment as a direct predictor of employees' psychological well-being and as a resource that buffers the adverse effects of self-control demands as a stressor. However, the mechanisms that underlie the beneficial effects of affective commitment have not been examined yet. Drawing on the self-determination theory, we propose day-specific flow experiences as the mechanism that underlies the beneficial effects of affective commitment, because flow experiences as peaks of intrinsic motivation constitute manifestations of autonomous regulation. In a diary study covering 10 working days with N = 90 employees, we examine day-specific flow experiences as a mediator of the beneficial effects of interindividual affective commitment and a buffering moderator of the adverse day-specific effects of self-control demands on indicators of well-being (ego depletion, need for recovery, work engagement, and subjective vitality). Our results provide strong support for our predictions that day-specific flow experiences a) mediate the beneficial effects of affective commitment on employees' day-specific well-being and b) moderate (buffer) the adverse day-specific effects of self-control demands on well-being. That is, on days with high levels of flow experiences, employees were better able to cope with self-control demands whereas self-control demands translated into impaired well-being when employees experienced lower levels of day-specific flow experiences. We then discuss our findings and suggest practical implications. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring? A prospective study over two decades.

PubMed

Danielsen, Inge; Granström, Charlotta; Rytter, Dorte; Hammer Bech, Bodil; Brink Henriksen, Tine; Vaag, Allan Arthur; Olsen, Sjurdur Frodi

2013-08-01

It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring. Longitudinal study where 965 pregnant women during 1988-1989 had four dimensions of PA assessed by questionnaires in gestation week 30: PA at work; leisure time PA, daily amount of walking-biking and sport participation. The following MS markers were assessed in the offspring (n=439): body mass index (BMI), waist circumference, blood pressure, homeostasis model assessment insulin resistance as well as fasting plasma glucose, triglycerides, cholesterol (high-density lipoprotein (HDL), low-density lipoprotein and total cholesterol), insulin and leptin levels. Walking-biking PA in pregnancy is associated with unchanged or subtle, adverse changes of distinct MS markers among offspring including lower levels of HDL cholesterol (ratio 0.95 (95% CI 0.92 to 0.98) per 1 h increment in walking-biking), a higher diastolic blood pressure (difference 1.12 (95% CI 0.03 to 2.20) mm Hg/1 h increment) and a higher BMI (ratio 1.03 (95% CI 1.01 to 1.05) per 1 h increment). In separate analyses in males, these associations persisted and additional adverse associations were found for triglycerides, systolic blood pressure, waist circumference and leptin. No associations were detected with other measures of PA. The study did not substantiate any protective effects of PA in pregnancy. In contrast, data suggested that high amounts of daily walking-biking in pregnancy may have adverse effects on levels of HDL cholesterol, diastolic blood pressure and BMI in young adult offspring.

A review on cardiovascular diseases originated from subclinical hypothyroidism.

PubMed

Mansourian, Azad Reza

2012-01-15

Thyroid hormones play an important role on the cardiovascular systems and thyroid disorder ultimately have a profound adverse effects on myocardium and vascular functions. There are extensive reports on the role of overt thyroid dysfunction which adversely can modify the cardiovascular metabolism but even at the present of some controversial reports, the subclinical thyroid disorders are able also to manipulate cardiovascular system to some extent. The aim of this study is to review the cardiovascular disorders accompanied with subclinical hypothyroidism. It is concluded that adverse effect of thyroid malfunction on myocardium and vascular organs are through the direct role of thyroid hormone and dyslipidemia on heart muscle cells at nuclear level and vascular system, respectively. It seems many cardiovascular disorders initially would not have been occurred in the first place if the thyroid of affected person had functioned properly, therefore thyroid function tests should be one of a prior laboratory examinations in cardiovascular disorders.

Potential hazards due to food additives in oral hygiene products.

PubMed

Tuncer Budanur, Damla; Yas, Murat Cengizhan; Sepet, Elif

2016-01-01

Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.

Russian Countermeasure Systems for Adverse Effects of Microgravity on Long-Duration ISS Flights.

PubMed

Kozlovskaya, Inessa B; Yarmanova, E N; Yegorov, A D; Stepantsov, V I; Fomina, E V; Tomilovaskaya, E S

2015-12-01

The system of countermeasures for the adverse effects of microgravity developed in the USSR supported the successful implementation of long-duration spaceflight (LDS) programs on the Salyut and Mir orbital stations and was subsequently adapted for flights on the International Space Station (ISS). From 2000 through 2010, crews completed 26 ISS flight increments ranging in duration from 140 to 216 d, with the participation of 27 Russian cosmonauts. These flights have made it possible to more precisely determine a crew-member's level of conditioning, better assess the advantages and disadvantages of training processes, and determine prospects for future developments.

Complementary and alternative exercise for fibromyalgia: a meta-analysis

PubMed Central

Mist, Scott David; Firestone, Kari A; Jones, Kim Dupree

2013-01-01

Complementary and alternative medicine includes a number of exercise modalities, such as tai chi, qigong, yoga, and a variety of lesser-known movement therapies. A meta-analysis of the current literature was conducted estimating the effect size of the different modalities, study quality and bias, and adverse events. The level of research has been moderately weak to date, but most studies report a medium-to-high effect size in pain reduction. Given the lack of adverse events, there is little risk in recommending these modalities as a critical component in a multimodal treatment plan, which is often required for fibromyalgia management. PMID:23569397

Tolerability of sirolimus: a decade of experience at a single cardiac transplant center.

PubMed

Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, William Steves; Peltz, Matthias; Drazner, Mark H

2013-01-01

Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Different drinking motives, different adverse consequences? Evidence among adolescents from 10 European countries.

PubMed

Wicki, Matthias; Kuntsche, Emmanuel; Eichenberger, Yvonne; Aasvee, Katrin; Bendtsen, Pernille; Dankulincová Veselská, Zuzana; Demetrovics, Zsolt; Dzielska, Anna; Farkas, Judit; de Matos, Margarida Gaspar; Roberts, Chris; Tynjälä, Jorma; Välimaa, Raili; Vieno, Alessio

2017-11-01

This study, which builds on previous research demonstrating that drinking motives are associated with adverse consequences, investigates the associations between drinking motives and non-alcohol-attributed adverse consequences and disentangles alcohol-related and direct effects. On the basis of a sample of 22 841 alcohol-using 13- to 16-year-olds (50.6% female) from Belgium, Denmark, Estonia, Finland, Ireland, Portugal, Scotland, Slovakia, Switzerland and Wales, structural equation models were used to estimate direct and indirect effects. Additionally, differences across countries were tested in a multigroup analysis. The indirect effect (via alcohol use) was greater for injuries and academic problems than for more general outcomes such as life dissatisfaction and negative body image. For social, enhancement and coping motives, we found positive indirect effects (via alcohol use) on injuries and academic problems; the association was negative for conformity motives. The direct effect, that is, the effect above and beyond alcohol use, indicated more negative consequences among those who tended to drink more frequently for coping motives. More negative consequences, such as injuries and negative body image, were also found among those who drink for conformity motives. The pattern of association was largely comparable across countries. While the actual mean level of drinking motives, alcohol use and adverse consequence varied across countries, the consistency of association patterns implies that drinking motive-inspired health promotion efforts are likely to be beneficial across Europe. This is particularly important for coping drinkers because they are especially prone to adverse consequences over and above their alcohol use. [Wicki M, Kuntsche E, Eichenberger Y, Aasvee K, Bendtsen P, Dankulincová Veselská Z, Demetrovics Z, Dzielska A, Farkas J, de Matos MG, Roberts C, Tynjälä J, Välimaa R, Vieno A. Different drinking motives, different adverse consequences? Evidence among adolescents from 10 European countries. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Lead toxicity: does the critical level of lead resulting in adverse effects differ between adults and children?

PubMed

Murata, Katsuyuki; Iwata, Toyoto; Dakeishi, Miwako; Karita, Kanae

2009-01-01

The Scientific Committee on Neurotoxicology and Psychophysiology and the Scientific Committee on the Toxicology of Metals of the International Commission on Occupational Health in 2006 recommended that the standard for blood lead (BPb) levels be reduced to 30 microg/dl for industrial workers and 5 microg/dl for children. To examine whether the critical level of lead producing adverse effects truly differs between workers and children, we provided an overview of studies addressing the critical level of lead in workers, together with a perspective on lead toxicity in children. In 25 reports published in English with keywords of "benchmark dose (BMD)," "lead" and "humans," only five studies proved to be relevant to lead toxicity. Four more studies with figures illustrating significant relationships between lead and neurotoxic outcomes were selected. Based on data from previous reports using a BMD approach, the critical organ of lead in workers was thought to be the nervous system and the critical BPb level (number-weighted mean) was between 10.7 and 17.5 microg/dl. The neurotoxic effects of lead exposure at such levels seemed reversible. The BPb level at which lead-associated intellectual deficits occurred in children was as low as the critical level of BPb (below 5 microg/dl) for inhibited heme synthesis in workers. The neurotoxic effects of lead in workers appear to be initiated at BPb levels below 18 microg/dl, which are somewhat higher than the critical level of lead neurotoxicity in children. Each national institute for risk management should take evidence-based preventive action against subclinical lead poisoning in workers, as well as in children.

Thiamethoxam honey bee colony feeding study: Linking effects at the level of the individual to those at the colony level.

PubMed

Overmyer, Jay; Feken, Max; Ruddle, Natalie; Bocksch, Sigrun; Hill, Marcus; Thompson, Helen

2018-03-01

Neonicotinoid insecticides have been used globally on a wide range of crops through seed treatment as well as soil and foliar applications and have been increasingly studied in relation to the potential risk to bees because of their detection in pollen and nectar of bee-attractive crops. The present article reports the results of laboratory studies (10-d adult and 22-d larval toxicity studies assessing the chronic toxicity of thiamethoxam to adult honey bees and larvae, respectively) and a colony feeding study, with 6 wk of exposure in an area with limited alternative forage, to provide a prewintering colony-level endpoint. The endpoints following exposure of individuals in the laboratory (10-d adult chronic no-observed-effect concentration [NOEC] for mortality 117 μg thiamethoxam/kg sucrose solution, 141 μg thiamethoxam/L sucrose solution; 22-d larval chronic NOEC 102 μg thiamethoxam/kg diet) are compared with those generated at the colony level, which incorporates sublethal effects (no-observed-adverse-effect concentration [NOAEC] 50 μg thiamethoxam/L sucrose solution, 43 μg thiamethoxam/kg sucrose solution). The data for sucrose-fed honey bee colonies support the lack of effects identified in previous colony-level field studies with thiamethoxam. However, unlike these field studies demonstrating no effects, colony feeding study data also provide a threshold level of exposure likely to result in adverse effects on the colony in the absence of alternative forage, and a basis by which to evaluate the potential risk of thiamethoxam residues detected in pollen, nectar, or water following treatment of bee-attractive crops. Environ Toxicol Chem 2018;37:816-828. © 2017 SETAC. © 2017 SETAC.

Health effects associated with passenger vehicles: monetary values of air pollution.

PubMed

Marzouk, Mohamed; Madany, Magdy

2012-01-01

Air pollution is regarded as one of the highest priorities in environmental protection in both developed and developing countries. High levels of air pollution have adverse effects on human health that might cause premature death. This study presents the monetary value estimates for the adverse human health effects resulted from ambient air pollution. It aids decision makers to set priorities in the public health relevance of pollution abatement. The main driver of policymaker is the need to reduce the avoidable cardiopulmonary morbidity and mortality from pollutant exposures. The monetary valuation involves 2 steps: (i) relate levels of pollutants to mortality and morbidity (concentration-response relationships) and (ii) apply unit economic values. Cost of air pollution associated with passenger vehicles running over a major traffic bridge (6th of October Elevated Highway) is presented as a case study to demonstrate the use of monetary value of air pollution. The study proves that the cost of air pollution is extremely high and should not be overlooked.

Low-level laser/light therapy for androgenetic alopecia.

PubMed

Gupta, Aditya K; Lyons, Danika C A; Abramovits, William

2014-01-01

Androgenetic alopecia (AGA) is a persistent and pervasive condition that affects men worldwide. Some common treatment options for AGA include hair prosthetics, oral and topical medications, and surgical hair restoration (SHR). Pharmaceutical and SHR treatments are associated with limitations including adverse side effects and significant financial burden. Low-level laser or light (LLL) devices offer alternative treatment options that are not typically associated with adverse side effects or significant costs. There are clinic- and home-based LLL devices. One home-based laser comb device has set a standard for others; however, this device requires time devoted to carefully moving the comb through the hair to allow laser penetration to the scalp. A novel helmet-like LLL device for hair growth has proven effective in preliminary trials and allows for hands-free use. Regardless, there are few clinical trials that have been conducted regarding LLL devices for AGA and results are mixed. Further research is required to establish the true efficacy of these devices for hair growth in comparison to existing alternative therapies.

The influence of endocrine disruptors on growth and development of children.

PubMed

DiVall, Sara A

2013-02-01

This review describes the most recent data about the effects of endocrine disrupting compounds (EDCs) on infant and early childhood growth and reproductive tract development as well as controversies in the field. EDCs are present in pregnant women, young children and adolescents. Whether the level of exposure contributes to disease is an ongoing debate. Epidemiological studies suggest associations between prenatal EDC exposure and disease outcome, but animal studies using controlled EDC exposure have varying results with underlying mechanisms largely unknown. Human exposure to EDCs is widespread; bisphenol A, phthalates and persistent organic pollutants are detectable in all age groups and geographical locations in the USA. Epidemiological and animal studies suggest that phthalates and bisphenol A have adverse effects on birth weight, promote development of childhood obesity and adversely affect male reproductive tract development. Differences in the interpretation of available studies underlie the disparate conclusions of scientific and regulatory body's panels on potential toxicological effects of EDCs at current levels of human exposure.

[Nearby nature as a moderator of stress during childhood].

PubMed

Corraliza, José Antonio; Collado, Silvia

2011-04-01

The aim of this investigation is to study the relation between the amount of nature existing in children's daily environments and the way children deal with stressful events. Every day, children are exposed to situations that cause stress. Taking into account previous studies, it is thought that the greener the place where children spend their time, the better they cope with adversities. Thus, when comparing the stress level of children who are exposed to the same amount of adverse situations, the children who have more frequent daily contact with nature will show less stress than those who do not spend time in nature. This effect from nearby nature is called a buffering effect. The present study provides empirical evidence of the buffering effect caused by the existence of Nature in the residential and the school environment. Therefore, our results show that children who have more access to nature increase their resilience, showing a lower stress level than children whose contact with nature is less frequent.

29 CFR 575.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

...; (iii) The level and type of pesticides and other chemicals used would not have an adverse effect on the... employed commute daily from their permanent residence to the farm on which they are so employed; and (iii...

29 CFR 575.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-07-01

...; (iii) The level and type of pesticides and other chemicals used would not have an adverse effect on the... employed commute daily from their permanent residence to the farm on which they are so employed; and (iii...

29 CFR 575.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

...; (iii) The level and type of pesticides and other chemicals used would not have an adverse effect on the... employed commute daily from their permanent residence to the farm on which they are so employed; and (iii...

29 CFR 575.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

...; (iii) The level and type of pesticides and other chemicals used would not have an adverse effect on the... employed commute daily from their permanent residence to the farm on which they are so employed; and (iii...

Failure or success of search strategies to identify adverse effects of medical devices: a feasibility study using a systematic review.

PubMed

Golder, Su; Wright, Kath; Rodgers, Mark

2014-10-13

Research has indicated that adverse effects terms are increasingly prevalent in the title, abstract or indexing terms of articles that contain adverse drug effects data in MEDLINE and Embase. However, it is unknown whether adverse effects terms are present in the database records of articles that contain adverse effects data of medical devices, and thus, to what extent the development of an adverse effects search filter for medical devices may be feasible. A case study systematic review of a medical device was selected. The included studies from a systematic review of the safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) for spinal fusion were used in the analysis. For each included study, the corresponding database record on MEDLINE and Embase was assessed to measure the presence or absence of adverse effects terms in the title, abstract or indexing. The performance of each potential adverse effects search term was also measured and compared. There were 82 publications (49 studies) included in the systematic review with 51 of these indexed on MEDLINE and 55 on Embase. Ninety-four percent (48/51) of the records on MEDLINE and 95% (52/55) of the records on Embase contained at least one adverse effects related search term. The wide variety of adverse effects terms included in the title, abstract or indexing of bibliographic records, and the lack of any individual high-performing search terms suggests that a combination of terms in different fields is required to identify adverse effects of medical devices. In addition, the most successful search terms differed from the most successful terms for identifying adverse drug effects. The search filters currently available for adverse drug effects are not necessarily useful for searching adverse effects data of medical devices. The presence of adverse effects terms in the bibliographic records of articles on medical devices, however, indicates that combinations of adverse effects search terms may be useful in search strategies in MEDLINE and Embase. The results, therefore, suggest that not only a search filter for the adverse effects of medical devices is feasible, but also that it should be a research priority.

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

PubMed

Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra

2017-06-15

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Are adverse effects incorporated in economic models? An initial review of current practice.

PubMed

Craig, D; McDaid, C; Fonseca, T; Stock, C; Duffy, S; Woolacott, N

2009-12-01

To identify methodological research on the incorporation of adverse effects in economic models and to review current practice. Major electronic databases (Cochrane Methodology Register, Health Economic Evaluations Database, NHS Economic Evaluation Database, EconLit, EMBASE, Health Management Information Consortium, IDEAS, MEDLINE and Science Citation Index) were searched from inception to September 2007. Health technology assessment (HTA) reports commissioned by the National Institute for Health Research (NIHR) HTA programme and published between 2004 and 2007 were also reviewed. The reviews of methodological research on the inclusion of adverse effects in decision models and of current practice were carried out according to standard methods. Data were summarised in a narrative synthesis. Of the 719 potentially relevant references in the methodological research review, five met the inclusion criteria; however, they contained little information of direct relevance to the incorporation of adverse effects in models. Of the 194 HTA monographs published from 2004 to 2007, 80 were reviewed, covering a range of research and therapeutic areas. In total, 85% of the reports included adverse effects in the clinical effectiveness review and 54% of the decision models included adverse effects in the model; 49% included adverse effects in the clinical review and model. The link between adverse effects in the clinical review and model was generally weak; only 3/80 (< 4%) used the results of a meta-analysis from the systematic review of clinical effectiveness and none used only data from the review without further manipulation. Of the models including adverse effects, 67% used a clinical adverse effects parameter, 79% used a cost of adverse effects parameter, 86% used one of these and 60% used both. Most models (83%) used utilities, but only two (2.5%) used solely utilities to incorporate adverse effects and were explicit that the utility captured relevant adverse effects; 53% of those models that included utilities derived them from patients on treatment and could therefore be interpreted as capturing adverse effects. In total, 30% of the models that included adverse effects used withdrawals related to drug toxicity and therefore might be interpreted as using withdrawals to capture adverse effects, but this was explicitly stated in only three reports. Of the 37 models that did not include adverse effects, 18 provided justification for this omission, most commonly lack of data; 19 appeared to make no explicit consideration of adverse effects in the model. There is an implicit assumption within modelling guidance that adverse effects are very important but there is a lack of clarity regarding how they should be dealt with and considered in modelling. In many cases a lack of clear reporting in the HTAs made it extremely difficult to ascertain what had actually been carried out in consideration of adverse effects. The main recommendation is for much clearer and explicit reporting of adverse effects, or their exclusion, in decision models and for explicit recognition in future guidelines that 'all relevant outcomes' should include some consideration of adverse events.

Evaluation of perampanel in patients with intellectual disability and epilepsy.

PubMed

Snoeijen-Schouwenaars, Francesca M; van Ool, Jans S; Tan, In Y; Schelhaas, Helenius J; Majoie, Marian H J M

2017-01-01

Initial registration studies of perampanel (PMP), an AMPA receptor antagonist, have now been followed up by 'clinical' studies that confirmed its efficacy and safety in patients with refractory epilepsy. Publications on the use of PMP among patients with intellectual disability (ID) are still limited. This study extends our knowledge with respect to the relevance of PMP for patients with both ID and epilepsy, and furthermore specifies the behavioral side effects of PMP in this specific population. Retrospective evaluation of medical records at 3, 6 and 12months of follow-up after the initial start of PMP. 62 patients were included. 21 patients (33.9%) were female. All patients had complete data of 6months follow-up and we were able to review 42 patients with a 1-year follow-up. Level of ID varied from borderline to profound, and mild ID was most common (43.5%). The mean maximum daily dosage of PMP was 5.6mg (range 1-12mg). Retention rates for PMP were 87.1% and 67.7% after three and six months. A trend indicated a longer mean retention time in patients with a more severe ID (borderline-mild-moderate ID: 205days, severe-profound ID: 275days). Seizure reduction was achieved in 53.2%. 36 patients (58.1%) experienced adverse effects, 80.6% of those within 3months. 45.2% of the patients experienced somatic adverse effects. Most common were fatigue & sleep problems, motor problems & unsteadiness, and gastrointestinal problems. Behavioral adverse effects were present in 40.3%. Most common were aggression, agitated behavior, disruptive behavior, and mood symptoms. Reasons for discontinuation of PMP were lack of efficacy in 14.8%, intolerable adverse effects in 44.4%, and a combination of both in 40.7%. Altogether, 24.2% (15/62) of the patients achieved seizure reduction without experiencing adverse effects, though none reached seizure freedom. The use of PMP might lead to an effective seizure reduction without adverse effects in a minority of patients with both epilepsy and ID. Pre-existing behavioral problems or polypharmacy do not predict the occurrence of additional behavioral adverse effects, implying that these patients need not be excluded from the introduction of PMP when clinically indicated. Patients should, ideally, be monitored at a multidisciplinary clinic. Copyright © 2016 Elsevier Inc. All rights reserved.

Developmental effects of exposures to environmental factors: the Polish Mother and Child Cohort Study.

PubMed

Polanska, Kinga; Hanke, Wojciech; Sobala, Wojciech; Trzcinka-Ochocka, Malgorzata; Ligocka, Danuta; Brzeznicki, Slawomir; Strugala-Stawik, Halina; Magnus, Per

2013-01-01

This paper estimates the effects of exposure to environmental factors, including lead, mercury, environmental tobacco smoke (ETS), and polycyclic aromatic hydrocarbons (PAH), on child psychomotor development. The study population consists of mother-child pairs in the Polish Mother and Child Cohort Study. Prenatal and postnatal exposure to environmental factors was determined from biomarker measurements as follows: for lead exposure--cord blood lead level, for mercury--maternal hair mercury level, for ETS--cotinine level in saliva and urine, and for PAH--1-hydroxypyrene (1-HP) in urine. At the age of 12 (406 subjects) and 24 months (198 subjects) children were assessed using Bayley Scales of Infant and Toddler Development. There were no statistically significant effects of prenatal exposure to mercury or 1-HP on child psychomotor development. After adjusting for potential confounders, adverse effects of prenatal exposure to ETS on motor development ( β = -2.6; P = 0.02) and postnatal exposure to ETS on cognitive ( β = -0.2; P = 0.05) and motor functions ( β = -0.5; P = 0.01) were found. The adverse effect of prenatal lead exposure on cognitive score was of borderline significance ( β = -6.2; P = 0.06). The study underscores the importance of policies and public health interventions that aim to reduce prenatal and postnatal exposure to lead and ETS.

NTP-CERHR monograph on the potential human reproductive and developmental effects of di (2-ethylhexyl) phthalate (DEHP).

PubMed

Shelby, Michael D

2006-11-01

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an updated evaluation of the potential for DEHP to cause adverse effects on reproduction and development in humans. The first CERHR expert panel evaluation of DEHP was completed in 2000 by the Phthalates Expert Panel. CERHR selected DEHP for an updated evaluation because of: (1) widespread human exposure, (2) public and government interest in adverse health effects, (3) recently available human exposure studies, and (4) the large number of relevant toxicity papers published since the earlier evaluation. DEHP (CAS RN: 117-81-7) is a high production volume chemical used as a plasticizer of polyvinyl chloride in the manufacture of a wide variety of consumer goods, such as building products, car products, clothing, food packaging, children's products (but not in toys intended for mouthing), and in medical devices made of polyvinyl chloride. The public can be exposed to DEHP by ingesting food, drink or dust that has been in contact with DEHP-containing materials, by inhaling contaminated air or dust, or by undergoing a medical procedure that uses polyvinyl chloride medical tubing or storage bags. It is estimated that the general population of the United States is exposed to DEHP levels ranging from 1 to 30 microg/kg bw/day (micrograms per kilogram body weight per day). The results of this DEHP update evaluation are published in an NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Update on the Reproductive and Developmental Toxicity of DEHP, and (3) public comments on the expert panel report. The NTP reached the following conclusions on the possible effects of exposure to DEHP on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. There is serious concern that certain intensive medical treatments of male infants may result in DEHP exposure levels that adversely affect development of the male reproductive tract. DEHP exposure from medical procedures in infants was estimated to be as high as 6000 microg/kg bw/day. There is concern for adverse effects on development of the reproductive tract in male offspring of pregnant and breast feeding women undergoing certain medical procedures that may result in exposure to high levels of DEHP. There is concern for effects of DEHP exposure on development of the male reproductive tract for infants less than one year old. Diet, mouthing of DEHP-containing objects, and certain medical treatments may lead to DEHP exposures that are higher than those experienced by the general population. There is some concern for effects of DEHP exposure on development of the reproductive tract of male children older than one year. As in infants, exposures of children to DEHP may be higher than in the general population. There is some concern for adverse effects of DEHP exposure on development of the male reproductive tract in male offspring of pregnant women not medically exposed to DEHP. Although DEHP exposures are assumed to be the same as for the general population, the developing male reproductive tract is sensitive to the adverse effects of DEHP. There is minimal concern for reproductive toxicity in adults exposed to DEHP at 1 - 30 microg/kg bw/day. This level of concern is not altered for adults medically exposed to DEHP. NTP will transmit the NTP-CERHR Monograph on DEHP to federal and state agencies, interested parties, and the public and it will be available in electronic PDF format on the CERHR web site http://cerhr.niehs.nih.gov and in printed text or CD-ROM from the CERHR.

Initial Experience with Balloon-Occluded Trans-catheter Arterial Chemoembolization (B-TACE) for Hepatocellular Carcinoma

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

Maruyama, Mitsunari, E-mail: mitunari@med-shimane.u.ac.jp; Yoshizako, Takeshi, E-mail: yosizako@med.shimane-u.ac.jp; Nakamura, Tomonori, E-mail: t-naka@med.shimane-u.ac.jp

2016-03-15

PurposeThis study was performed to evaluate the accumulation of lipiodol emulsion (LE) and adverse events during our initial experience of balloon-occluded trans-catheter arterial chemoembolization (B-TACE) for hepatocellular carcinoma (HCC) compared with conventional TACE (C-TACE).MethodsB-TACE group (50 cases) was compared with C-TACE group (50 cases). The ratio of the LE concentration in the tumor to that in the surrounding embolized liver parenchyma (LE ratio) was calculated after each treatment. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Effects (CTCAE) version 4.0.ResultsThe LE ratio at the level of subsegmental showed a statistically significant difference between the groups (tmore » test: P < 0.05). Only elevation of alanine aminotransferase was more frequent in the B-TACE group, showing a statistically significant difference (Mann–Whitney test: P < 0.05). While B-TACE caused severe adverse events (liver abscess and infarction) in patients with bile duct dilatation, there was no statistically significant difference in incidence between the groups. Multivariate logistic regression analysis suggested that the significant risk factor for liver abscess/infarction was bile duct dilatation (P < 0.05).ConclusionThe LE ratio at the level of subsegmental showed a statistically significant difference between the groups (t test: P < 0.05). B-TACE caused severe adverse events (liver abscess and infarction) in patients with bile duct dilatation.« less

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Adverse effects of aromatherapy: a systematic review of case reports and case series.

PubMed

Posadzki, Paul; Alotaibi, Amani; Ernst, Edzard

2012-01-01

This systematic review was aimed at critically evaluating the evidence regarding the adverse effects associated with aromatherapy. Five electronic databases were searched to identify all relevant case reports and case series. Forty two primary reports met our inclusion criteria. In total, 71 patients experienced adverse effects of aromatherapy. Adverse effects ranged from mild to severe and included one fatality. The most common adverse effect was dermatitis. Lavender, peppermint, tea tree oil and ylang-ylang were the most common essential oils responsible for adverse effects. Aromatherapy has the potential to cause adverse effects some of which are serious. Their frequency remains unknown. Lack of sufficiently convincing evidence regarding the effectiveness of aromatherapy combined with its potential to cause adverse effects questions the usefulness of this modality in any condition.

Neighborhood Collective Efficacy Moderates the Association between Maternal Adverse Childhood Experiences and Marital Conflict.

PubMed

Madigan, Sheri; Wade, Mark; Plamondon, André; Jenkins, Jennifer M

2016-06-01

In a socio-demographically diverse sample of 501 caregivers participating in a longitudinal birth cohort study during the childbearing years, we examined whether neighborhood collective efficacy moderated the association between maternal adverse childhood experience (ACEs) and marital conflict. Maternal ACEs were assessed via retrospective reports. Neighborhood collective efficacy was measured via maternal and paternal reports at 2 months, and maternal reports of marital conflict were collected at infant age 2 and 18 months. Multiple linear regression analyses revealed that maternal ACEs were associated with increased marital conflict. Neighborhood collective efficacy moderated the association between early maternal ACEs and marital conflict, such that mothers experiencing ACEs had lower levels of marital conflict when exposed to high levels of neighborhood collective efficacy. Results suggest that extra-familial sources of social support and control, such as feelings of security, trust, order, and connectedness with others, may buffer the effects of early adversity on marital discord. © Society for Community Research and Action 2016.

Impact of socioeconomic status on survival of colorectal cancer patients.

PubMed

Zhang, Qian; Wang, Yufu; Hu, Hanqing; Huang, Rui; Xie, Lei; Liu, Enrui; Chen, Ying-Gang; Wang, Guiyu; Wang, Xishan

2017-12-01

Socioeconomic status (SES) has an impact on the survival of various cancers, but it has not been fully understood in colorectal cancer (CRC). The Surveillance, Epidemiology and End Results database was adopted to detect the role of SES in the survival outcomes of CRC. A total of 184,322 eligible patients were included and SES status was analyzed. The multivariable analysis showed that Non-Hispanic Black (HR, 1.20; 95% CI, 1.15-1.24), being widowed (HR, 1.04; 95% CI, 1.01-1.07), any Medicaid (HR, 1.36; 95% CI, 1.33-1.39) and the lowest education level group patients had relative poorer prognosis. Besides, sex, tumor location, age, differentiation level and American Joint Committee on Cancer stage also had significant effects on overall survival of CRC. The individuals were further divided into five groups according to the number of survival-adverse factors. All of the four groups containing adverse factors showed impaired survival outcomes compared with the group containing no adverse factor.

Perceived risk, stigma, and potential economic impacts of a high-level nuclear waste repository in Nevada

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

Slovic, P.; Layman, M.; Kraus, N.N.

1989-07-01

This paper describes a program of research designed to assess the potential impacts of a high-level nuclear waste repository at Yucca Mountain, Nevada, upon tourism, retirement and job-related migration, and business development in Las Vegas and the state. Adverse economic impacts may be expected to result from two related social processes. One has to do with perceptions of risk and socially amplified reactions to ``unfortunate events`` associated with the repository (major and minor accidents, discoveries of radiation releases, evidence of mismanagement, attempts to sabotage or disrupt the facility, etc.). The second process that may trigger significant adverse impacts is thatmore » of stigmatization. The conceptual underpinnings of risk perception, social amplification, and stigmatization are discussed in this paper and empirical data are presented to demonstrate how nuclear images associated with Las Vegas and the State of Nevada might trigger adverse effects on tourism, migration, and business development.« less

Effects of Three Levels of Early Intervention Services on Children Prenatally Exposed to Cocaine

ERIC Educational Resources Information Center

Claussen, Angelika H.; Scott, Keith G.; Mundy, Peter C.; Katz, Lynne F.

2004-01-01

Cocaine use during pregnancy is a high-risk indicator for adverse developmental outcomes. Three levels of intervention (center, home, and primary care) were compared in a full service, birth to age 3, early intervention program serving children exposed to cocaine prenatally. Data were collected on 130 children from urban, predominantly poor,…

On-Road Chemical Transformation as an Important Mechanism of NO2 Formation

EPA Science Inventory

Nitrogen dioxide (NO2) not only is linked with a number of adverse effects on the respiratory system, but also contributes to the formation of ground-level ozone (O3) and fine particulate matter (PM2.5) pollution. NO2 levels near major roads have been monitored as part of the one...

The Effect of Neighborhood Context on the Drug Use of American Indian Youth of the Southwest

PubMed Central

Yabiku, Scott T.; Rayle, Andrea Dixon; Okamoto, Scott K.; Marsiglia, Flavio F.; Kulis, Stephen

2011-01-01

SUMMARY This study examined neighborhood effects on the drug use of American Indian youth of the Southwest. We compared these effects with American Indian and non-American Indian youth in order to examine the universality of neighborhood disorganization as a risk factor for drug use. Neighborhood level variables included unemployment, poverty, education, and violent crime rate. Results indicated that American Indian youth were not as adversely affected by these neighborhood factors. American Indian youth may possess cultural characteristics that protect them from the adverse effects of neighborhood disorganization, including close familial relationships and ethnic pride. Culturally competent practice with American Indian youth may best be implemented through the enhancement of relational and cultural strengths as described in the literature. PMID:18192210

Stress sensitization and adolescent depressive severity as a function of childhood adversity: a link to anxiety disorders.

PubMed

Espejo, Emmanuel P; Hammen, Constance L; Connolly, Nicole P; Brennan, Patricia A; Najman, Jake M; Bor, William

2007-04-01

The goal of the present study was to determine whether exposure to adversity in childhood contributes to a differential threshold at which stressful life events provoke depressive reactions in adolescence. In addition, to address empirical and conceptual questions about stress effects, the moderating effect of anxiety disorder history was also explored. This examination was conducted in a sample of 816 children of depressed and nondepressed mothers, who were followed from birth to age 15. Information on adversities experienced in childhood was collected both from mothers during the first five years of their youth's life and from the youths themselves at age 15, and included information on the mother's relationship with her partner, maternal psychopathology, as well as youth-reported abuse. Results indicated that youths with both greater exposure to adversity in childhood and a history of an anxiety disorder displayed increased depressive severity following low levels of episodic stress compared to youths with only one or neither of these risk factors. The results are speculated to reflect the possibility that early anxiety disorders associated with exposure to adversity in childhood may be a marker of dysregulated stress responses, and may help to account for the comorbidity of depression and anxiety in some individuals.

Psychological resilience and the gene regulatory impact of posttraumatic stress in Nepali child soldiers.

PubMed

Kohrt, Brandon A; Worthman, Carol M; Adhikari, Ramesh P; Luitel, Nagendra P; Arevalo, Jesusa M G; Ma, Jeffrey; McCreath, Heather; Seeman, Teresa E; Crimmins, Eileen M; Cole, Steven W

2016-07-19

Adverse social conditions in early life have been linked to increased expression of proinflammatory genes and reduced expression of antiviral genes in circulating immune cells-the conserved transcriptional response to adversity (CTRA). However, it remains unclear whether such effects are specific to the Western, educated, industrialized, rich, and democratic (WEIRD) cultural environments in which previous research has been conducted. To assess the roles of early adversity and individual psychological resilience in immune system gene regulation within a non-WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child soldiers and matched noncombatant civilians 5 y after the People's War in Nepal. CTRA gene expression was up-regulated in former child soldiers. These effects were linked to the degree of experienced trauma and associated distress-that is, posttraumatic stress disorder (PTSD) severity-more than to child soldier status per se. Self-perceived psychological resilience was associated with marked buffering of CTRA activation such that PTSD-affected former child soldiers with high levels of personal resilience showed molecular profiles comparable to those of PTSD-free civilians. These results suggest that CTRA responses to early life adversity are not restricted to WEIRD cultural contexts and they underscore the key role of resilience in determining the molecular impact of adverse environments.

Toxicology of haloacetonitriles

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

Hayes, J.R.; Condie, L.W. Jr.; Borzelleca, J.F.

1986-11-01

Haloacetonitriles are by-products of water chlorination and may form in vivo from the reaction of residual chlorine with endogenous compounds such as amino acids. Dibromoacetonitrile (DBAN) was negative in selected mutagenic assays; dichloroacetonitrile (DCAN) was mutagenic in S. typhimurium, but not in S. cerevisiae. Both DBAN and DCAN may be carcinogenic. The studies described were conducted to determined the acute, subacute, and subchronic toxicity of DBAN and DCAN. The acute oral LD/sub 50/ values (mg/kg) in mice and rats are: DBAN, mice: 289 (M), 303 (F); DBAN, rats: 245 (M), 361 (F); DCAN, mice: 270 (M), 279 (F); DCAN, rats:more » 339 (M), 330 (F). Death was preceded by slowed respiration, depressed activity, prostration, and coma. There were no apparent compound-related gross pathological effects. DBAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 23, 45, 90, and 180 mg/kg/day or 6, 23, and 45 mg/kg/day, respectively. No consistent, significant, adverse compound-related effects on any of the parameters evaluated were evident. Possible target organs might be spleen, thymus, and liver. The no-observed adverse-effect level (NOAEL) for 14 days was 45 mg/kg/day and for 90 days was 23 mg/kg/day. DCAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 12, 23, 45, and 90 mg/kg/day or 8, 33, and 65 mg/kg/day, respectively. There were not deaths during the 14 day study. No consistent, significant adverse compound-related effects on any of the parameters evaluated were evident. The NOAEL for 14 days was 45 mg/kg/day and for 90 days was 9 mg/kg/day.« less

Capability of different non-nutritive feed additives on improving productive and physiological traits of broiler chicks fed diets with or without aflatoxin during the first 3 weeks of life.

PubMed

Attia, Y A; Allakany, H F; Abd Al-Hamid, A E; Al-Saffar, A A; Hassan, R A; Mohamed, N A

2013-08-01

An experiment was conducted to determine whether some non-nutritive feed additives (NNFA) could block the adverse effects of aflatoxin (AF) on growth performance and physiological parameters of Cobb broilers throughout the period from 1 to 21 day of age. There were eight treatments consisting of two levels of AF at 0 and 200 ppb and four NNFA within each AF level. These additives included mannan oligosaccharides (MOS) at 2 g/kg diet, hydrated sodium calcium aluminosilicate (HSCAS) at 2 g/kg diet and Lactobacillus acidophilus (Lac) at 2 g/kg diet. At 21 day of age, five chickens of each treatment were slaughtered to study dressing percentage and relative weight of inner organs and glands. AF had a significant negative effect on body weight gain (BWG), and feed intake, while impairing feed conversion ratio (FCR). Aflatoxin significantly increased percentage liver, lymphocyte (%), monocyte (%), serum triglyceride level, and the aspartate aminotransferase (AST), and alanine aminotransferase (ALT), concentrations while decreasing dressing percentage, intestinal percentage, white blood cells (WBCs), red blood cells (RBCs), haemoglobin (Hgb), packed cell volume (PCV), heterophil (%), heterophil/lymphocyte ratio, total serum protein and serum albumin. Aflatoxin adversely affected the morphology of the liver, bursa and the thymus. There was a significant interaction between AF and NNFA on the relative weights of liver, heart and intestine. Lac completely blocked the negative effects of AF on the percentage liver and the heart and partially on the intestine. In conclusion, Lac was most effective in reversing the adverse effects of AF on growth and FCR and on the percentage, functions and morphology of the liver. Hydrated sodium calcium aluminosilicate also improved the economic traits of broilers but was less effective than Lac and more effective than MOS. © 2012 Blackwell Verlag GmbH.

Bacoside A: Role in Cigarette Smoking Induced Changes in Brain

PubMed Central

Vani, G.; Anbarasi, K.; Shyamaladevi, C. S.

2015-01-01

Cigarette smoking (CS) is a major health hazard that exerts diverse physiologic and biochemical effects mediated by the components present and generated during smoking. Recent experimental studies have shown predisposition to several biological consequences from both active and passive cigarette smoke exposure. In particular, passive smoking is linked to a number of adverse health effects which are equally harmful as active smoking. A pragmatic approach should be considered for designing a pharmacological intervention to combat the adverse effects of passive smoking. This review describes the results from a controlled experimental condition, testing the effect of bacoside A (BA) on the causal role of passive/secondhand smoke exposure that caused pathological and neurological changes in rat brain. Chronic exposure to cigarette smoke induced significant changes in rat brain histologically and at the neurotransmitter level, lipid peroxidation states, mitochondrial functions, membrane alterations, and apoptotic damage in rat brain. Bacoside A is a neuroactive agent isolated from Bacopa monnieri. As a neuroactive agent, BA was effective in combating these changes. Future research should examine the effects of BA at molecular level and assess its functional effects on neurobiological and behavioral processes associated with passive smoke. PMID:26413118

Bacoside A: Role in Cigarette Smoking Induced Changes in Brain.

PubMed

Vani, G; Anbarasi, K; Shyamaladevi, C S

2015-01-01

Cigarette smoking (CS) is a major health hazard that exerts diverse physiologic and biochemical effects mediated by the components present and generated during smoking. Recent experimental studies have shown predisposition to several biological consequences from both active and passive cigarette smoke exposure. In particular, passive smoking is linked to a number of adverse health effects which are equally harmful as active smoking. A pragmatic approach should be considered for designing a pharmacological intervention to combat the adverse effects of passive smoking. This review describes the results from a controlled experimental condition, testing the effect of bacoside A (BA) on the causal role of passive/secondhand smoke exposure that caused pathological and neurological changes in rat brain. Chronic exposure to cigarette smoke induced significant changes in rat brain histologically and at the neurotransmitter level, lipid peroxidation states, mitochondrial functions, membrane alterations, and apoptotic damage in rat brain. Bacoside A is a neuroactive agent isolated from Bacopa monnieri. As a neuroactive agent, BA was effective in combating these changes. Future research should examine the effects of BA at molecular level and assess its functional effects on neurobiological and behavioral processes associated with passive smoke.

A realistic in vitro exposure revealed seasonal differences in (pro-)inflammatory effects from ambient air in Fribourg, Switzerland.

PubMed

Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

2018-01-01

Ambient air pollutant levels vary widely in space and time, therefore thorough local evaluation of possible effects is needed. In vitro approaches using lung cell cultures grown at the air-liquid interface and directly exposed to ambient air can offer a reliable addition to animal experimentations and epidemiological studies. To evaluate the adverse effects of ambient air in summer and winter a multi-cellular lung model (16HBE14o-, macrophages, and dendritic cells) was exposed in a mobile cell exposure system. Cells were exposed on up to three consecutive days each 12 h to ambient air from Fribourg, Switzerland, during summer and winter seasons. Higher particle number, particulate matter mass, and nitrogen oxide levels were observed in winter ambient air compared to summer. Good cell viability was seen in cells exposed to summer air and short-term winter air, but cells exposed three days to winter air were compromised. Exposure of summer ambient air revealed no significant upregulation of oxidative stress or pro-inflammatory genes. On the opposite, the winter ambient air exposure led to an increased oxidative stress after two exposure days, and an increase in three assessed pro-inflammatory genes already after 12 h of exposure. We found that even with a short exposure time of 12 h adverse effects in vitro were observed only during exposure to winter but not summer ambient air. With this work we have demonstrated that our simple, fast, and cost-effective approach can be used to assess (adverse) effects of ambient air.

Effects of Music Intervention on State Anxiety and Physiological Indices in Patients Undergoing Mechanical Ventilation in the Intensive Care Unit.

PubMed

Lee, Chiu-Hsiang; Lee, Chien-Ying; Hsu, Ming-Yi; Lai, Chiung-Ling; Sung, Yi-Hui; Lin, Chung-Ying; Lin, Long-Yau

2017-03-01

Patients in intensive care units (ICUs) often experience stress and anxiety. Although stress and anxiety can be pharmacologically attenuated, some drugs cause adverse side effects such as bradycardia, immobility, and delirium. There is thus a need for an alternative treatment with no substantial adverse effects. Music intervention is a potential alternative. In the present study, we used cortisol levels, subjective questionnaires, and physiological parameters to explore the anxiety-reducing effects of music intervention in a sample of ICU patients on mechanical ventilation. Patients admitted to the ICU for ≥ 24 hr were randomly assigned to the music intervention ( n = 41) or control group ( n = 44). Music group patients individually listened to music from 4:00 to 4:30 p.m.; control group patients wore headphones but heard no music for the same 30 min. Anxiety was measured using serum cortisol levels, the Chinese Version of the State-Trait Anxiety Inventory, the Visual Analogue Scale for Anxiety, heart rate, and blood pressure. After adjusting for demographics, analysis of covariance showed that the music group had significantly better scores for all posttest measures ( p < .02) and pre-post differences ( p < .03) except for diastolic blood pressure. Because of music intervention's low cost and easy administration, clinical nurses may want to use music to reduce stress and anxiety for ICU patients. A single 30-min session might work immediately without any adverse effects. However, the duration of the effect is unclear; thus, each patient's mood should be monitored after the music intervention.

Comparative toxicity study of 3-aminophenol in newborn and young rats.

PubMed

Koizumi, Mutsuko; Nishimura, Nobuo; Enami, Tomonori; Sunaga, Masao; Horikawa, Hironao; Kamata, Eiichi; Hasegawa, Ryuichi

2002-12-01

Repeated dose toxicity of 3-aminophenol was examined on oral administration to newborn and young rats, and susceptibility was analyzed in terms of the no observed adverse effect level (NOAEL) and the unequivocally toxic level. In the 18-day newborn rat study, starting at day 4 after birth, tremors and depression of body weight gain were observed, as well as hypertrophy of thyroid follicular epithelial cells and increases of relative liver and kidney weights at 240 mg/kg. Increase of relative liver weights in males and decrease of blood sugar in females without any histopathological changes at 80 mg/kg were not considered to be adverse effects. No chemical-related changes were observed at 24 mg/kg. Abnormalities of external development and reflex ontogeny in the newborn were not observed. In the 28-day study, starting at 5 weeks of age, depression of body weight gain, tremors, anemia, and liver, kidney and thyroid toxicity were observed at 720 mg/kg. Although slight pigmentation in the renal proximal tubular epithelium was observed in females at 240 mg/kg, this was not considered to be an adverse effect because of the lack of changes in related toxicological parameters. It was concluded that the NOAEL is 80 mg/kg/day in newborn rats and 240 mg/kg/day in young rats, with unequivocally toxic levels of 240 mg/kg/day and 720 mg/kg/day, respectively. Based on these two endpoints, the susceptibility of newborn rats to the chemical was approx. 3 times higher than that of young rats, consistent with our previous results for 4-nitrophenol and 2,4-dinitrophenol.

Alleviation of salt stress in lemongrass by salicylic acid.

PubMed

Idrees, Mohd; Naeem, M; Khan, M Nasir; Aftab, Tariq; Khan, M Masroor A; Moinuddin

2012-07-01

Soil salinity is one of the key factors adversely affecting the growth, yield, and quality of crops. A pot study was conducted to find out whether exogenous application of salicylic acid could ameliorate the adverse effect of salinity in lemongrass (Cymbopogon flexuosus Steud. Wats.). Two Cymbopogon varieties, Krishna and Neema, were used in the study. Three salinity levels, viz, 50, 100, and 150 mM of NaCl, were applied to 30-day-old plants. Salicylic acid (SA) was applied as foliar spray at 10(-5) M concentration. Totally, six SA-sprays were carried out at 10-day intervals, following the first spray at 30 days after sowing. The growth parameters were progressively reduced with the increase in salinity level; however, growth inhibition was significantly reduced by the foliar application of SA. With the increase in salt stress, a gradual decrease in the activities of carbonic anhydrase and nitrate reductase was observed in both the varieties. SA-treatment not only ameliorated the adverse effects of NaCl but also showed a significant improvement in the activities of these enzymes compared with the untreated stressed-plants. The plants supplemented with NaCl exhibited a significant increase in electrolyte leakage, proline content, and phosphoenol pyruvate carboxylase activity. Content and yield of essential oil was also significantly decreased in plants that received salinity levels; however, SA overcame the unfavorable effects of salinity stress to a considerable extent. Lemongrass variety Krishna was found to be more adapted to salt stress than Neema, as indicated by the overall performance of the two varieties under salt conditions.

Blood transcriptomics: applications in toxicology

PubMed Central

Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

2015-01-01

The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

Determining the effects of a mixture of an endocrine disrupting compound, 17α-ethinylestradiol, and ammonia on fathead minnow (Pimephales promelas) reproduction.

PubMed

Armstrong, Brandon M; Lazorchak, James M; Murphy, Cheryl A; Haring, Herman J; Jensen, Kathleen M; Smith, Mark E

2015-02-01

Aquatic organisms are exposed to a multitude of contaminants and to fully understand the impact of multiple stressors on fish populations, we must first understand the mechanism of action for each toxicant and how the combined effects manifest at the level of the individual. 17α-ethinylestradiol (EE2) has been known to cause adverse reproductive effects including reduced fecundity and fertility, intersex and skewed sex ratios in fish by mimicking naturally produced estrogen at low concentrations. Ammonia can cause adverse reproductive and mortality effects in individual fish through effects or damage to the central nervous system. Both EE2 and ammonia are found in most municipal effluents in various concentrations. A flow-through diluter system was used to test the individual effects of these two contaminants at their respective no observable adverse effect concentration (NOAEC) as well as their combined effects on fathead minnow, (Pimephales promelas) reproduction in a mixture exposure. While neither contaminant nor their mixture altered reproduction in terms of fecundity, their mixture resulted in significant fathead minnow mortality during a 21 d exposure. This study demonstrated the need to consider mixture effects when assessing risk for toxicity testing with multiple stressors. Published by Elsevier Ltd.

Ameliorating the biological impacts of childhood adversity: A review of intervention programs.

PubMed

Purewal Boparai, Sukhdip K; Au, Vanessa; Koita, Kadiatou; Oh, Debora Lee; Briner, Susan; Burke Harris, Nadine; Bucci, Monica

2018-05-01

Childhood adversity negatively impacts the biological development of children and has been linked to poor health outcomes across the life course. The purpose of this literature review is to explore and evaluate the effectiveness of interventions that have addressed an array of biological markers and physical health outcomes in children and adolescents affected by adversity. PubMed, CINAHL, PsychInfo, Sociological Abstracts databases and additional sources (Cochrane, WHO, NIH trial registries) were searched for English language studies published between January 2007 and September 2017. Articles with a childhood adversity exposure, biological health outcome, and evaluation of intervention using a randomized controlled trial study design were selected. The resulting 40 intervention studies addressed cortisol outcomes (n = 20) and a range of neurological, epigenetic, immune, and other outcomes (n = 22). Across institutional, foster care, and community settings, intervention programs demonstrated success overall for improving or normalizing morning and diurnal cortisol levels, and ameliorating the impacts of adversity on brain development, epigenetic regulation, and additional outcomes in children. Factors such as earlier timing of intervention, high quality and nurturant parenting traits, and greater intervention engagement played a role in intervention success. This study underlines progress and promise in addressing the health impacts of adversity in children. Ongoing research efforts should collect baseline data, improve retention, replicate studies in additional samples and settings, and evaluate additional variables, resilience factors, mediators, and long-term implications of results. Clinicians should integrate lessons from the intervention sciences for preventing and treating the health effects of adversity in children and adolescents. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Use of Severity Grades to Characterize Histopathologic Changes

EPA Science Inventory

The severity grade is an important component of a histopathologic diagnosis in a nonclinical toxicity study that helps distinguish treatment-related effects from background findings and aids in determining adverse dose levels during hazard characterization. Severity grades should...

Neuropsychological Motor Outcomes in Adults from Airborne Manganese Exposure

EPA Science Inventory

Background: The literature on manganese (Mn) is dominated by occupational exposures of adults exposed often to high levels without protection. Neuropsychological adverse health effects are similar to Parkinson’s Disease with psychomotor slowing, tremor, cognitive and mood ...

Adverse health effects in Canada geese (Branta canadensis) associated with waste from zinc and lead mines in the Tri-State Mining District (Kansas, Oklahoma, and Missouri, USA).

PubMed

van der Merwe, Deon; Carpenter, James W; Nietfeld, Jerome C; Miesner, John F

2011-07-01

Lead and zinc poisoning have been recorded in a variety of bird species, including migrating waterfowl such as Canada Geese (Branta canadensis), at sites contaminated with mine waste from lead and zinc mines in the Tri-State Mining District, Kansas, Oklahoma, and Missouri, USA. The adverse health impacts from mine waste on these birds may, however, be more extensive than is apparent from incidental reports of clinical disease. To characterize health impacts from mine waste on Canada Geese that do not have observable signs of poisoning, four to eight apparently healthy birds per site were collected from four contaminated sites and an uncontaminated reference site, and examined for physical and physiologic evidence of metals poisoning. Tissue concentrations of silver, aluminum, arsenic, barium, cadmium, cobalt, chromium, copper, iron, magnesium, manganese, molybdenum, nickel, lead, selenium, thallium, vanadium, and zinc were determined by inductively coupled plasma mass spectroscopy. Adverse health effects due to lead were characterized by assessing blood δ-aminolevulinic acid dehydratase (ALAD) enzyme activity. Adverse effects associated with zinc poisoning were determined from histologic examination of pancreas tissues. Elevated tissue lead concentrations and inhibited blood ALAD enzyme activities were consistently found in birds at all contaminated sites. Histopathologic signs of zinc poisoning, including fibrosis and vacuolization, were associated with elevated pancreatic zinc concentrations at one of the study sites. Adverse health effects associated with other analyzed elements, or tissue concentrations indicating potentially toxic exposure levels to these elements, were not observed.

40 CFR 230.70 - Actions concerning the location of the discharge.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Actions To Minimize Adverse Effects § 230.70 Actions concerning the location of the discharge. The effects...) Designing the discharge to avoid a disruption of periodic water inundation patterns; (c) Selecting a... minimize or prevent the creation of standing bodies of water in areas of normally fluctuating water levels...

Higher Secondary Learners' Effectiveness towards Web Based Instruction (WBI) on Chemistry

ERIC Educational Resources Information Center

Sudha, A.; Amutha, S.

2015-01-01

Web-based training is becoming a phenomenon in education today because of its flexibility and convenience, it is vitally important to address those issues that adversely impact retention and success in this environment. To generate principles of effective asynchronous web-based materials specifically applicable for secondary level students based…

DIESEL EXHAUST PARTICLES SUPRESS LPS-STIMULATED PRODUCTION OF PGE2 IN HUMAN ALVEOLAR MACHROPHAGES: ROLE OF P38 MAPK AND ERK PATHWAYS

EPA Science Inventory

Numerous studies have reported association between exposure to ambient levels of particulate matter (PM) and adverse health effects, which include respiratory and cardiovascular effects. Diesel exhaust particles (DEP) compose a significant fraction of PM in some areas. Alveolar m...

High but not low ECS stimulus intensity augments apomorphine-stimulated dopamine postsynaptic receptor functioning in rats.

PubMed

Andrade, Chittaranjan; Srinivasamurthy, Gurunath M; Vishwasenani, A; Prakash, G Sai; Srihari, B S; Chandra, J Suresh

2002-06-01

Clinical research shows that the antidepressant and cognitive adverse effects of electroconvulsive therapy are both dependent on the administered electrical stimulus intensity (dose); however, dose-dependent neurotransmitter system changes in the brain, which might underlie the therapeutic or adverse effects, remain to be demonstrated. We used a behavioral model to examine dose-related effects of electroconvulsive shock (ECS) on dopamine postsynaptic receptor functioning in the rat brain. In a factorially designed study, rats (n = 100) were treated with five once-daily ECSs at three levels (sham ECS, 30 mC ECS, and 120 mC ECS), and with drug at two levels (saline, and 1 mg/kg s.c. apomorphine). Motility was assessed in the small open field. Apomorphine-elicited, dopamine postsynaptic receptor-mediated hypermotility was significantly increased by 120 mC ECS but not by 30 mC ECS. An additional but unrelated finding was that, while the ECS seizure duration expectedly decreased across time, no dose-dependent effects were observed. ECS-induced dopamine postsynaptic receptor up-regulation may depend on the intensity of the administered electrical stimulus.

An Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Factor ADMA

PubMed Central

Ghebremariam, Yohannes T.; LePendu, Paea; Lee, Jerry C.; Erlanson, Daniel A.; Slaviero, Anna; Shah, Nigam H.; Leiper, James; Cooke, John P.

2013-01-01

Background Proton pump inhibitors (PPIs) are gastric acid suppressing agents widely prescribed for the treatment of gastro-esophageal reflux disease (GERD). Recently, several studies in patients with acute coronary syndrome (ACS) have raised the concern that use of PPIs in these patients may increase their risk of major adverse cardiovascular events (MACE). The mechanism of this possible adverse effect is not known. Whether the general population might also be at risk has not been addressed. Methods and Results Plasma ADMA is an endogenous inhibitor of nitric oxide synthase (NOS). Elevated plasma ADMA is associated with increased risk for cardiovascular disease, likely due to its attenuation of the vasoprotective effects of endothelial NOS. We find that PPIs elevate plasma asymmetric dimethylarginine (ADMA) level and reduce nitric oxide (NO) levels and endothelium-dependent vasodilation in a murine model and ex vivo human tissues. PPIs increase ADMA because they bind to, and inhibit dimethylarginine dimethylaminohydrolase (DDAH), the enzyme that degrades ADMA. Conclusions We present a plausible biological mechanism to explain the association of PPIs with increased MACE in patients with unstable coronary syndromes. Of concern, this adverse mechanism is also likely to extend to the general population using PPIs. This finding compels additional clinical investigations and pharmacovigilance directed toward understanding the cardiovascular risk associated with use of the PPIs in the general population. PMID:23825361

Ecological risk assessment for DvSnf7 RNA: A plant-incorporated protectant with targeted activity against western corn rootworm.

PubMed

Bachman, Pamela M; Huizinga, Kristin M; Jensen, Peter D; Mueller, Geoffrey; Tan, Jianguo; Uffman, Joshua P; Levine, Steven L

2016-11-01

MON 87411 maize, which expresses DvSnf7 RNA, was developed to provide an additional mode of action to confer protection against corn rootworm (Diabrotica spp.). A critical step in the registration of a genetically engineered crop with an insecticidal trait is performing an ecological risk assessment to evaluate the potential for adverse ecological effects. For MON 87411, an assessment plan was developed that met specific protection goals by characterizing the routes and levels of exposure, and testing representative functional taxa that would be directly or indirectly exposed in the environment. The potential for toxicity of DvSnf7 RNA was evaluated with a harmonized battery of non-target organisms (NTOs) that included invertebrate predators, parasitoids, pollinators, soil biota as well as aquatic and terrestrial vertebrate species. Laboratory tests evaluated ecologically relevant endpoints such as survival, growth, development, and reproduction and were of sufficient duration to assess the potential for adverse effects. No adverse effects were observed with any species tested at, or above, the maximum expected environmental concentration (MEEC). All margins of exposure for NTOs were >10-fold the MEEC. Therefore, it is reasonable to conclude that exposure to DvSnf7 RNA, both directly and indirectly, is safe for NTOs at the expected field exposure levels. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Interim methods for development of inhalation reference concentrations. Draft report

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

Blackburn, K.; Dourson, M.; Erdreich, L.

1990-08-01

An inhalation reference concentration (RfC) is an estimate of continuous inhalation exposure over a human lifetime that is unlikely to pose significant risk of adverse noncancer health effects and serves as a benchmark value for assisting in risk management decisions. Derivation of an RfC involves dose-response assessment of animal data to determine the exposure levels at which no significant increase in the frequency or severity of adverse effects between the exposed population and its appropriate control exists. The assessment requires an interspecies dose extrapolation from a no-observed-adverse-effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL(HBC)).more » The RfC is derived from the NOAEL(HBC) by the application of generally order-of-magnitude uncertainty factors. Intermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. Relationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorption, distribution, metabolism, storage, detoxification, and elimination. To estimate NOAEL(HBC)s when chemical-specific physiologically-based pharmacokinetic models are not available, a dosimetric extrapolation procedure based on anatomical and physiological parameters of the exposed human and animal and the physical parameters of the toxic chemical has been developed which gives equivalent or more conservative exposure concentrations values than those that would be obtained with a PB-PK model.« less

Chronic effects of air pollution on respiratory health in Southern California children: findings from the Southern California Children's Health Study.

PubMed

Chen, Zhanghua; Salam, Muhammad T; Eckel, Sandrah P; Breton, Carrie V; Gilliland, Frank D

2015-01-01

Outdoor air pollution is one of the leading contributors to adverse respiratory health outcomes in urban areas around the world. Children are highly sensitive to the adverse effects of air pollution due to their rapidly growing lungs, incomplete immune and metabolic functions, patterns of ventilation and high levels of outdoor activity. The Children's Health Study (CHS) is a continuing series of longitudinal studies that first began in 1993 and has focused on demonstrating the chronic impacts of air pollution on respiratory illnesses from early childhood through adolescence. A large body of evidence from the CHS has documented that exposures to both regional ambient air and traffic-related pollutants are associated with increased asthma prevalence, new-onset asthma, risk of bronchitis and wheezing, deficits of lung function growth, and airway inflammation. These associations may be modulated by key genes involved in oxidative-nitrosative stress pathways via gene-environment interactions. Despite successful efforts to reduce pollution over the past 40 years, air pollution at the current levels still brings many challenges to public health. To further ameliorate adverse health effects attributable to air pollution, many more toxic pollutants may require regulation and control of motor vehicle emissions and other combustion sources may need to be strengthened. Individual interventions based on personal susceptibility may be needed to protect children's health while control measures are being implemented.

The epidemiology and possible mechanisms of disinfection by-products in drinking water.

PubMed

Nieuwenhuijsen, Mark J; Grellier, James; Smith, Rachel; Iszatt, Nina; Bennett, James; Best, Nicky; Toledano, Mireille

2009-10-13

This paper summarizes the epidemiological evidence for adverse health effects associated with disinfection by-products (DBPs) in drinking water and describes the potential mechanism of action. There appears to be good epidemiological evidence for a relationship between exposure to DBPs, as measured by trihalomethanes (THMs), in drinking water and bladder cancer, but the evidence for other cancers including colorectal cancer is inconclusive and inconsistent. There appears to be some evidence for an association between exposure to DBPs, specifically THMs, and little for gestational age/intrauterine growth retardation and, to a lesser extent, pre-term delivery, but evidence for relationships with other outcomes such as low birth weight, stillbirth, congenital anomalies and semen quality is inconclusive and inconsistent. Major limitations in exposure assessment, small sample sizes and potential biases may account for the inconclusive and inconsistent results in epidemiological studies. Moreover, most studies have focused on total THMs as the exposure metric, whereas other DBPs appear to be more toxic than the THMs, albeit generally occurring at lower levels in the water. The mechanisms through which DBPs may cause adverse health effects including cancer and adverse reproductive effects have not been well investigated. Several mechanisms have been suggested, including genotoxicity, oxidative stress, disruption of folate metabolism, disruption of the synthesis and/or secretion of placental syncytiotrophoblast-derived chorionic gonadotropin and lowering of testosterone levels, but further work is required in this area.

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2011-01-01

Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized 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. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

Thalidomide induces haematologic responses in patients with β-thalassaemia.

PubMed

Chen, Jiangming; Zhu, Weijian; Cai, Ning; Bu, Shengdi; Li, Jinyan; Huang, Lan

2017-11-01

This study aimed to evaluate the clinical and laboratory outcomes of a group of patients with β-thalassaemia major or intermedia treated with thalidomide. Clinical and laboratory data were obtained by analysing medical records of β-thalassaemia patients. Using the self-control method, the levels of haemoglobin (Hb), foetal haemoglobin (HbF), white blood cells (WBC) and platelets were detected before and after the treatment, and adverse reactions were recorded. Data from the medical records of 9 patients were analysed. The median haemoglobin levels of these patients increased from 5.13 ± 2.15 g/dL before treatment to 10.38 ± 1.19 g/dL after treatment. The average spleen size decreased from a pretreatment length of 8.19 ± 3.10 to 5.49 ± 1.80 cm below the costal margin after treatment. The mean HbF levels increased from a pretreatment value of 35.67% ± 26.82% to 75.67% ± 14.64% after treatment in the 9 patients for whom these measurements were available. All patients no longer needed transfusions by 1 month after treatment. No serious adverse reactions were observed in any of the thalidomide-treated patients. In this study, thalidomide showed an outstanding effect on β-thalassaemia patients who required frequent red-cell transfusions. Thalidomide increased haemoglobin levels without causing serious adverse reactions, but the long-term curative outcomes and other side effects should be observed continuously. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combining contamination indexes, sediment quality guidelines and multivariate data analysis for metal pollution assessment in marine sediments of Cienfuegos Bay, Cuba.

PubMed

Peña-Icart, Mirella; Pereira-Filho, Edenir Rodrigues; Lopes Fialho, Lucimar; Nóbrega, Joaquim A; Alonso-Hernández, Carlos; Bolaños-Alvarez, Yoelvis; Pomares-Alfonso, Mario S

2017-02-01

The purpose of the present work was to combine several tools for assessing metal pollution in marine sediments from Cienfuegos Bay. Fourteen surface sediments collected in 2013 were evaluated. Concentrations of As, Cu, Ni, Zn and V decreased respect to those previous reported. The metal contamination was spatially distributed in the north and south parts of the bay. According to the contamination factor (CF) enrichment factor (EF) and index of geoaccumulation (I geo ), Cd and Cu were classified in that order as the most contaminated elements in most sediment. Comparison of the total metal concentrations with the threshold (TELs) and probable (PELs) effect levels in sediment quality guidelines suggested a more worrisome situation for Cu, of which concentrations were occasional associated with adverse biological effects in thirteen sediments, followed by Ni in nine sediments; while adverse effects were rarely associated with Cd. Probably, Cu could be considered as the most dangerous in the whole bay because it was classified in the high contamination levels by all indexes and, simultaneously, associated to occasional adverse effects in most samples. Despite the bioavailability was partially evaluated with the HCl method, the low extraction of Ni (<3% in all samples) and Cu (<55%, except sample 3) and the relative high extraction of Cd (50% or more, except sample 14) could be considered as an attenuating (Ni and Cu) or increasing (Cd) factor in the risk assessment of those element. Copyright © 2016. Published by Elsevier Ltd.

Uric Acid Level Has a U-shaped Association with Clinical Outcomes in Patients with Vasospastic Angina.

PubMed

Gwag, Hye Bin; Yang, Jeong Hoon; Park, Taek Kyu; Song, Young Bin; Hahn, Joo Yong; Choi, Jin Ho; Lee, Sang Hoon; Gwon, Hyeon Cheol; Choi, Seung Hyuk

2017-08-01

No data are available on the association of serum uric acid and vasospastic angina (VSA) which has endothelial dysfunction as a possible pathophysiologic mechanism. Low uric acid level might cause adverse outcomes in VSA in connection with endothelial dysfunction. We enrolled 818 VSA patients whose uric acid level was measured at admission. Patients were categorized according to tertiles of uric acid level: group I, ≤ 4.8 mg/dL; group II, 4.9-5.9 mg/dL; and group III, ≥ 6.0 mg/dL. Primary outcome was major adverse cardiac events (MACEs), defined as a composite of cardiac death, acute myocardial infarction (MI), ischemic stroke, coronary revascularization, and rehospitalization for angina. Median follow-up duration was 49.2 months. Median uric acid values were 4.1 mg/dL for group I, 5.4 mg/dL for group II, and 6.7 mg/dL for group III. In the overall population, group II had a significantly lower incidence of MACE compared to group I (47 [17.1%] vs. 66 [24.6%]; hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.02-2.26; P = 0.040) and a tendency of lower incidence of MACEs compared to Group III (47 [17.1%] vs. 62 [22.5%]; HR, 1.44; 95% CI, 0.98-2.13; P = 0.067). Among group I patients, those who received nitrates had a higher incidence of MACEs than those without nitrate therapy (P < 0.001). Low uric acid level was associated with adverse clinical outcomes, while high uric acid level had a trend toward an increase in it. Use of nitrate in patients with low uric acid level might have adverse effects on clinical outcomes of VSA. © 2017 The Korean Academy of Medical Sciences.

Studies of lead exposure on reproductive system: a review of work in China.

PubMed

Xuezhi, J; Youxin, L; Yilan, W

1992-09-01

This paper, based on a review of a series studies conducted in China from 1978 through 1991, describes the possible links between low level lead exposure and the adverse effects on reproductive system. Effects on menstrual status and pregnancy outcome manifested mainly as higher prevalences of menstrual disturbance, spontaneous abortion and threatened abortion in exposed females. Transfer of lead via placenta and human milk was shown by higher lead levels in milk and blood of infant. Impairment of male reproductive function was observed as decreased volume of ejaculation, prolonged latency of semen melting, reduced total sperm count and alive spermatozoa, retarded sperm activity as well as lowered density of semen fluid in exposed male workers with Pb-B over 40 micrograms.dl-1. In addition, poorer performance of WISC-R test was revealed in children with Pb-B level over 30 micrograms.dl-1, and retarded physical development was observed in children with Pb-B over 20 micrograms.dl-1. Therefore, health surveillance including the assessment of adverse effects on reproductive system of both female and male lead exposed workers should not be ignored. Furthermore, safety exposure limit of work place, particularly for female workers of child-bearing age, should be developed.

Use of short-term toxicity data for prediction of long-term health effects

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

Hartley, W.R.; Ohanian, E.V.

1988-01-01

Under the Safe Drinking Water Act Amendments of 1986, the US Environmental Protection Agency determines Maximum Contaminant Level Goals (MCLGs) and enforceable Maximum Contaminant Levels (MCLs) or provides lifetime health advisories (HAs) in the absence of regulatory standards. The critical value for calculation of the lifetime level is the reference dose (RfD). The RfD is an estimate of a lifetime dose which is likely to be without significant risk to human populations. The RfD is determined by dividing the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level (LOAEL) by an uncertainty factor (UF). The NOAEL or LOAEL is determined from toxicologicalmore » or epidemiological studies. For many chemicals, human toxicological or epidemiological data are not available. Chronic mammalian studies are sometimes unavailable. Faced with the need for providing guidance for the increasing number of chemicals threatening our drinking water sources, this paper considers the possibility of providing provisional RfDs using data from toxicological studies of less than ninety days duration. The current UF approach is reviewed along with some proposed mathematical models for extrapolation of NOAELs from dose-response data. The current UF approach to developing the RfD is protective and conservative. More research is needed on the relationship of short- and long-term toxicity data to improve our current approach.« less

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.

The role of nonverbal cognitive ability in the association of adverse life events with dysfunctional attitudes and hopelessness in adolescence.

PubMed

Flouri, Eirini; Panourgia, Constantina

2012-10-01

The aim of this study was to test whether nonverbal cognitive ability buffers the effect of life stress (number of adverse life events in the last year) on diatheses for depression. It was expected that, as problem-solving aptitude, nonverbal cognitive ability would moderate the effect of life stress on those diatheses (such as dysfunctional attitudes) that are depressogenic because they represent deficits in information-processing or problem-solving skills, but not on diatheses (such as hopelessness) that are depressogenic because they represent deficits in motivation or effort to apply problem-solving skills. The sample included 558 10- to 19-year-olds from a state secondary school in London. Nonverbal cognitive ability was negatively associated with both dysfunctional attitudes and hopelessness. As expected, nonverbal cognitive ability moderated the association between life adversity and dysfunctional attitudes. However, hopelessness was not related to life stress, and therefore, there was no life stress effect for nonverbal cognitive ability to moderate. This study adds to knowledge about the association between problem-solving ability and depressogenic diatheses. By identifying life stress as a risk factor for dysfunctional attitudes but not hopelessness, it highlights the importance of considering outcome specificity in models predicting adolescent outcomes from adverse life events. Importantly for practice, it suggests that an emphasis on recent life adversity will likely underestimate the true level of hopelessness among adolescents. Copyright © 2012 Elsevier Inc. All rights reserved.

Derivation of an occupational exposure level for manganese in welding fumes.

PubMed

Bailey, Lisa A; Kerper, Laura E; Goodman, Julie E

2018-01-01

Exposure to high levels of manganese (Mn) in occupational settings is known to lead to adverse neurological effects. Since Mn is an essential nutrient, there are mechanisms that maintain its homeostatic control in the body, and there is some level of Mn in air that does not perturb Mn homeostasis. However, the Mn exposure concentrations at which no adverse effects are expected in occupational settings vary considerably across regulatory agencies. We set out to derive a Mn Occupational Exposure Level (OEL) for welders based on a review of studies that evaluated Mn exposure concentrations from welding fumes and: (1) neurological effects in welders; (2) levels of Mn in the brains of welders (via pallidal index [PI] estimated from magnetic resonance imaging [MRI]); (3) other biomarkers of Mn exposure in welders (i.e., blood and urine); and (4) Mn brain concentrations, PI, and corresponding neurological effects in non-human primates. Our analysis suggests uncertainty in quantifying dose-response associations for Mn from many of the occupational welding studies. The few welding studies that adequately estimate exposure suggest a possible OEL of 100-140μg/m 3 for respirable Mn. This range is consistent with other epidemiology studies, studies of biomarkers of Mn exposure in welders, and with studies in non-human primates, though future studies could provide a stronger basis for deriving a Mn occupational guideline for welders. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity Studies: Results from the 5th ESTP International Expert Workshop.

PubMed

Lenz, B; Braendli-Baiocco, A; Engelhardt, J; Fant, P; Fischer, H; Francke, S; Fukuda, R; Gröters, S; Harada, T; Harleman, H; Kaufmann, W; Kustermann, S; Nolte, T; Palazzi, X; Pohlmeyer-Esch, G; Popp, A; Romeike, A; Schulte, A; Lima, B Silva; Tomlinson, L; Willard, J; Wood, C E; Yoshida, M

2018-02-01

Lysosomes have a central role in cellular catabolism, trafficking, and processing of foreign particles. Accumulation of endogenous and exogenous materials in lysosomes represents a common finding in nonclinical toxicity studies. Histologically, these accumulations often lack distinctive features indicative of lysosomal or cellular dysfunction, making it difficult to consistently interpret and assign adverse dose levels. To help address this issue, the European Society of Toxicologic Pathology organized a workshop where representative types of lysosomal accumulation induced by pharmaceuticals and environmental chemicals were presented and discussed. The expert working group agreed that the diversity of lysosomal accumulations requires a case-by-case weight-of-evidence approach and outlined several factors to consider in the adversity assessment, including location and type of cell affected, lysosomal contents, severity of the accumulation, and related pathological effects as evidence of cellular or organ dysfunction. Lysosomal accumulations associated with cytotoxicity, inflammation, or fibrosis were generally considered to be adverse, while those found in isolation (without morphologic or functional consequences) were not. Workshop examples highlighted the importance of thoroughly characterizing the biological context of lysosomal effects, including mechanistic data and functional in vitro readouts if available. The information provided here should facilitate greater consistency and transparency in the interpretation of lysosomal effects.

Cannabis: an overview of its adverse acute and chronic effects and their implications.

PubMed

Ford, Talitha C; Hayley, Amie C; Downey, Luke A; Parrott, Andrew C

2017-07-12

In many communities, cannabis is perceived as a low-risk drug, leading to political lobbying to decriminalise its use. However, acute and chronic cannabis use has been shown to be harmful to several aspects of psychological and physical health, such as mood states, psychiatric outcomes, neurocognition, driving and general health. Furthermore, cannabis is highly addictive, and the adverse effects of withdrawal can lead to regular use. These in turn have adverse implications for public safety and health expenditure. Although the cannabinoid cannabidiol (CBD) has been shown to have positive health outcomes with its antioxidant, anticonvulsant, anti-inflammatory and neuroprotective properties, high-potency cannabis is particularly damaging due to its high tetrahydrocannabinol (THC), low CDB concentration. It is this high-potency substance that is readily available recreationally. While pharmaceutical initiatives continue to investigate the medical benefits of CDB, "medicinal cannabis" still contains damaging levels of THC. Altogether, we argue there is insufficient evidence to support the safety of cannabis and its subsequent legalisation for recreational use. Furthermore, its use for medicinal purposes should be done with care. We argue that the public conversation for the legalisation of cannabis must include scientific evidence for its adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Conceptual model for assessing criteria air pollutants in a multipollutant context: A modified adverse outcome pathway approach.

PubMed

Buckley, Barbara; Farraj, Aimen

2015-09-01

Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is difficult since components are present in different combinations and concentrations in ambient air. Recent mechanistic studies have limited utility because of the inability to link measured changes to adverse outcomes that are relevant to risk assessment. New approaches are needed to address this challenge. The purpose of this manuscript is to describe a conceptual model, based on the adverse outcome pathway approach, which connects initiating events at the cellular and molecular level to population-wide impacts. This may facilitate hazard assessment of air pollution mixtures. In the case reports presented here, airway hyperresponsiveness and endothelial dysfunction are measurable endpoints that serve to integrate the effects of individual criteria air pollutants found in inhaled mixtures. This approach incorporates information from experimental and observational studies into a sequential series of higher order effects. The proposed model has the potential to facilitate multipollutant risk assessment by providing a framework that can be used to converge the effects of air pollutants in light of common underlying mechanisms. This approach may provide a ready-to-use tool to facilitate evaluation of health effects resulting from exposure to air pollution mixtures. Published by Elsevier Ireland Ltd.

Adverse conditions at the workplace are associated with increased suicide risk.

PubMed

Baumert, Jens; Schneider, Barbara; Lukaschek, Karoline; Emeny, Rebecca T; Meisinger, Christa; Erazo, Natalia; Dragano, Nico; Ladwig, Karl-Heinz

2014-10-01

The present study addressed potential harms of a negative working environment for employed subjects. The main aim was to evaluate if adverse working conditions and job strain are related to an increase in suicide mortality. The study population consisted of 6817 participants drawn from the MONICA/KORA Augsburg, Germany, surveys conducted in 1984-1995, being employed at baseline examination and followed up on average for 12.6 years. Adverse working conditions were assessed by an instrument of 16 items about chronobiological, physical and psychosocial conditions at the workplace, job strain was assessed as defined by Karasek. Suicide risks were estimated by Cox regression adjusted for suicide-related risk factors. A number of 28 suicide cases were observed within follow-up. High levels of adversity in chronobiological/physical working conditions significantly increased the risk for suicide mortality (HR 3.28, 95% CI 1.43-7.54) compared to low/intermediate levels in a model adjusted for age, sex and survey (p value 0.005). Additional adjustment for living alone, low educational level, smoking, high alcohol consumption, obesity and depressed mood attenuated this effect (HR 2.73) but significance remained (p value 0.022). Adverse psychosocial working conditions and job strain, in contrast, had no impact on subsequent suicide mortality risk (p values > 0.200). A negative working environment concerning chronobiological or physical conditions at the workplace had an unfavourable impact on suicide mortality risk, even after controlling for relevant suicide-related risk factors. Employer interventions aimed to improve workplace conditions might be considered as a suitable means to prevent suicides among employees. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prognostic role of heart-type fatty acid binding protein in pulmonary embolism: a meta-analysis.

PubMed

Liu, Mingjie; Yuan, Xia; Qiu, Xianming; Shan, Xiaoxi; Lin, Dianjie; Zhu, Ling

2015-01-01

Pulmonary embolism (PE) has a high morbidity and mortality. Hence it is important to recognize factors associated with higher risk of adverse outcomes in hemodynamically stable patients. Heart-type fatty acid binding protein (H-FABP) is a novel marker evaluated in recent years for prognosis in acute PE. Our aim was to evaluate the available evidence on the accuracy of H-FABP for predicting the prognosis of adverse clinical outcomes (defined as the occurrence of any of the following: death, cardiopulmonary resuscitation, endotracheal intubation, use of vasopressors, thrombolysis, surgical embolectomy, or admission to the intensive care unit) or mortality in patients with acute PE. Unrestricted searches of PubMed, the Cochrane Library, Web of Science and Science Direct were performed using the terms of "H-FABP" or "heart-type fatty acid binding protein" and ("pulmonary embolism" or "pulmonary thromboembolism"). A random-effect model was used to pool study results; χ(2) and I(2) testing was used to test for heterogeneity. Data of six studies were included in this analysis. 34 of 119(28.57%; 95%CI, 20.42%-36.72%) patients with elevated H-FABP levels had adverse events during follow-up compared with 24 of 475 (5.05%; 95%CI, 3.08%-7.02%) patients with normal levels. High H-FABP levels were associated with a high risk of occurrence of adverse clinical outcome (pooled OR, 10.81; 95%CI, 3.92-29.83). The results of this meta-analysis indicate that H-FABP is a good predictor for adverse outcomes in patients with acute PE. Copyright © 2014 Elsevier Ltd. All rights reserved.

Encouraging CPAP adherence: it is everyone's job.

PubMed

Bollig, Suzanne M

2010-09-01

Obstructive sleep apnea (OSA) is a chronic disease treated effectively with the use of continuous positive airway pressure (CPAP) therapy. Patient adherence to prescribed CPAP is variable, however, leaving the undertreated OSA patient at risk of development or worsening of comorbid medical conditions, including hypertension and cardiovascular disease. The severity of disease and the presence of daytime sleepiness appear to have some predictive quality for subsequent adherence, though a search for consistent predictive factors related to CPAP adherence has proven elusive. Other influences, such as sex, age, socioeconomic status, and personality traits are less robust predictors. The use of sophisticated therapy modalities such as auto-titration or bi-level PAP units has been shown to improve adherence in certain subsets of OSA patients. Adverse effects such as nasal congestion, dry mouth, or skin irritation occur in approximately 50% of CPAP users, and addressing these adverse effects may improve adherence in some patients. More encouraging, studies on the use of intensive patient education and behavioral interventions have shown more positive effects on adherence, leading to the conclusion that improvement in patient adherence to CPAP therapy requires a multi-layered approach, using combined technological, behavioral, and adverse-effect interventions.

Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

PubMed

Kovesdy, Csaba P; Matsushita, Kunihiro; Sang, Yingying; Brunskill, Nigel J; Carrero, Juan J; Chodick, Gabriel; Hasegawa, Takeshi; Heerspink, Hiddo L; Hirayama, Atsushi; Landman, Gijs W D; Levin, Adeera; Nitsch, Dorothea; Wheeler, David C; Coresh, Josef; Hallan, Stein I; Shalev, Varda; Grams, Morgan E

2018-05-01

Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health.

PubMed

Minatoya, Machiko; Naka Jima, Sonomi; Sasaki, Seiko; Araki, Atsuko; Miyashita, Chihiro; Ikeno, Tamiko; Nakajima, Tamie; Goto, Yuko; Kishi, Reiko

2016-09-15

Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23 and 41weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6ng/ml, neonatal TSH and FT4 was 2.20 μU/ml and 2.03ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary. Copyright © 2016. Published by Elsevier B.V.

Interaction between childhood adversity and functional polymorphisms in the dopamine pathway on first-episode psychosis.

PubMed

Trotta, Antonella; Iyegbe, Conrad; Yiend, Jenny; Dazzan, Paola; David, Anthony S; Pariante, Carmine; Mondelli, Valeria; Colizzi, Marco; Murray, Robin M; Di Forti, Marta; Fisher, Helen L

2018-04-10

There is consistent evidence of a cumulative relationship between childhood adversity and psychosis, with number of adversities experienced increasing the probability of psychosis onset. It is possible that genetic factors moderate the association between childhood adversity and psychosis, potentially by influencing how an individual reacts biologically and/or psychologically following exposure to adversity, in such a way as to set them off on the path to psychosis. However, identifying the specific genetic variants involved and how they interact with childhood adversity remains challenging. We examined whether the association between cumulative exposure to childhood adversity and development of psychotic disorder was moderated by the COMT Val 158 Met, AKT1 rs2494732 or DRD2 rs1076560 polymorphisms, known to affect dopamine levels. Participants were 285 first-presentation psychosis cases and 256 geographically-matched controls drawn from the Genetics and Psychosis (GAP) study. Childhood adversity was assessed using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and blood- and cheek-derived genotype data were collected. Our findings revealed no main effect of COMT Val 158 Met, AKT1 rs2494732 and DRD2 rs1076560 polymorphisms on psychosis case status or reports of childhood adversity. Individuals reporting a history of multiple adversities were more likely to be psychosis patients than controls, regardless of their genetic risk. There was no evidence of candidate genotype by childhood adversity interactions in relation to psychosis onset. These findings did not provide evidence of a possible role of COMT Val 158 Met, AKT1 rs2494732 or DRD2 rs1076560 genotypes in modifying the association between childhood adversity and onset of psychosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review.

PubMed

Costello, Michael F; Shrestha, Bhushan; Eden, John; Johnson, Neil P; Sjoblom, Peter

2007-05-01

The object of this review was to compare metformin versus oral contraceptive pill (OCP) treatment in polycystic ovary syndrome. A systematic review and meta-analysis employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was undertaken. Four randomized controlled trials (RCTs) (104 subjects) were included. Limited data demonstrated no evidence of a difference in effect between metformin and the OCP on hirsutism, acne or development of type 2 diabetes mellitus. There were no trials assessing diagnosis of cardiovascular disease or endometrial cancer. Metformin, in comparison with the OCP, was less effective in improving menstrual pattern [Peto odds ratio (OR) 0.08, 95% confidence interval (CI) 0.01-0.45) and in reducing the serum total testosterone level weighted mean difference (WMD) 0.54, 95% CI 0.22-0.86] but more effective in reducing fasting insulin (WMD -3.46, 95% CI - 5.39 to -1.52) and not increasing fasting triglyceride (WMD -0.48, 95% CI - 0.86 to -0.09) levels. Limited data demonstrated no evidence of a difference in effect between the two therapies on reducing fasting glucose or total cholesterol levels and severe adverse events. The limited RCT evidence to date does not show adverse metabolic risk with the use of the OCP compared with metformin. Further long-term RCTs are required.

Review shows that early foetal alcohol exposure may cause adverse effects even when the mother consumes low levels.

PubMed

Sarman, Ihsan

2018-06-01

Studies are increasingly focusing on the effects of prenatal alcohol exposure (PAE) on child health. The aim of this review was to provide paediatricians with new insights to help them communicate key messages about avoiding alcohol during pregnancy. Inspired by the 7th International Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating research, policy and practice, we studied English language papers published since 2010 on how early PAE triggered epigenetic mechanisms that had an impact on the development of some chronic diseases. We also report the findings of a human study using three-dimensional photography of the face to explore associations between PAE and craniofacial phenotyping. Animal models with different alcohol exposure patterns show that early PAE may lead to long-term chronic effects, due to developmental programming for some adult diseases in cardiovascular, metabolic and renal systems. The study with three-dimensional photographing is very promising in helping paediatricians to understand how even small amounts of PAE can affect craniofacial phenotyping. Even low levels of PAE can cause adverse foetal effects and not just in the brain. It is not currently possible to determine a safe period and level when alcohol consumption would not affect the foetus. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Comparison of gene expression changes induced by biguanides in db/db mice liver.

PubMed

Heishi, Masayuki; Hayashi, Koji; Ichihara, Junji; Ishikawa, Hironori; Kawamura, Takao; Kanaoka, Masaharu; Taiji, Mutsuo; Kimura, Toru

2008-08-01

Large-scale clinical studies have shown that the biguanide drug metformin, widely used for type 2 diabetes, to be very safe. By contrast, another biguanide, phenformin, has been withdrawn from major markets because of a high incidence of serious adverse effects. The difference in mode of action between the two biguanides remains unclear. To gain insight into the different modes of action of the two drugs, we performed global gene expression profiling using the livers of obese diabetic db/db mice after a single administration of phenformin or metformin at levels sufficient to cause a significant reduction in blood glucose level. Metformin induced modest expression changes, including G6pc in the liver as previously reported. By contrast, phenformin caused changes in expression level of many additional genes. We used a knowledge-based bioinformatic analysis to study the effects of phenformin. Differentially expressed genes identified in this study constitute a large gene network, which may be related to cell death, inflammation or wound response. Our results suggest that the two biguanides show a similar hypoglycemic effect in db/db mice, but phenformin induces a greater stress on the liver even a short time after a single administration. These findings provide a novel insight into the cause of the relatively high occurrence of serious adverse effect after phenformin treatment.

Establishing the Biological Relevance of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels

EPA Science Inventory

Phthalate esters (PEs) constitute a large class of compounds that are used for many consumer product applications. Many of the C2-C7 di-ortho PEs reduce fetal testicular hormone and gene expression levels in rats resulting in adverse effects seen later in life but it appears that...

Impact of a More Stringent Blood Lead Level Recommendation for Children (Ages 1-5): Vulnerabilities Related to Housing, Food Security, Vitamins, and Environmental Toxicants

EPA Science Inventory

The adverse health effects of lead (Pb) exposure in young children are well known. Non-Hispanic black children historically have higher blood Pb levels (BLL) compared to Mexican-Americans and non- Hispanic white children (CDC-MMWR). In the past, BLL tests below 10 µg/dL m...

Physical Environmental Adversity and the Protective Role of Maternal Monitoring in Relation to Early Child Conduct Problems

ERIC Educational Resources Information Center

Supplee, Lauren H.; Unikel, Emily B.; Shaw, Daniel S.

2007-01-01

Research on the development of externalizing behaviors during early childhood has focused on child and parenting factors. Fewer studies have investigated effects of aversive features of the micro-level physical environment, such as overcrowding and chaos in the home, and the macro-level environment, such as neighborhood quality. This study extends…

A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a ‘hierarchical anatomical classification schema’ which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects. PMID:29494708

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

PubMed

Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

Ultrasonographic evaluation of vincristine-induced gastric hypomotility and the prokinetic effect of mosapride in dogs.

PubMed

Tsukamoto, A; Ohno, K; Tsukagoshi, T; Maeda, S; Nakashima, K; Fukushima, K; Fujino, Y; Takeuchi, A; Tsujimoto, H

2011-01-01

Vincristine induces gastrointestinal motility disorders in humans. Adverse gastrointestinal events are commonly observed in dogs receiving vincristine. To evaluate gastric motility after vincristine administration in dogs and the prophylactic effect of a prokinetic agent, mosapride. Five healthy Beagle dogs. Five dogs received vincristine i.v. at a dosage of 0.75 mg/m(2). The motility index (MI) of the antral contraction was ultrasonographically evaluated 30 minutes postfeeding before administration of vincristine and for 6 days after vincristine treatment. After a 6-week washout period, the dogs received vincristine with mosapride (2 mg/kg p.o., q24h for 6 days), and the MI was re-evaluated. Adverse gastrointestinal events were evaluated according to the Veterinary Co-operative Group Common Terminology Criteria for Adverse Events (VCOG-CTCAE). After vincristine administration, a significant decrease (P < .05) in MI was observed on days 3 (6.64 ± 0.30) and 4 (8.02 ± 0.94), compared with pretreatment levels (10.00 ± 0.62). Gastrointestinal adverse events were observed in 4 dogs (grade 2 decreased appetite: 3 dogs; grade 1 vomiting: 2 dogs; and grade 1 diarrhea and grade 2 hematochezia: 1 dog). When mosapride citrate was administered with vincristine and for the next 5 days, no decrease in MI was observed. Furthermore, adverse gastrointestinal events occurred less frequently (grade 1 vomiting and grade 2 hematochezia in 1 dog each). Vincristine (0.75 mg/m(2)) induces gastric hypomotility in dogs. Preventive administration of mosapride citrate (2.0 mg/kg p.o., q24h) improves hypomotility and may decrease the adverse gastrointestinal effects of vincristine. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Human environmental and occupational exposures to boric acid: reconciliation with experimental reproductive toxicity data.

PubMed

Bolt, Hermann M; Başaran, Nurşen; Duydu, Yalçın

2012-01-01

The reproductive toxicity of boric acid and borates is a matter of current regulatory concern. Based on experimental studies in rats, no-observed-adverse-effect levels (NOAELs) were found to be 17.5 mg boron (B)/kg body weight (b.w.) for male fertility and 9.6 mg B/kg b.w. for developmental toxicity. Recently, occupational human field studies in highly exposed cohorts were reported from China and Turkey, with both studies showing negative results regarding male reproduction. A comparison of the conditions of these studies with the experimental NOAEL conditions are based on reported B blood levels, which is clearly superior to a scaling according to estimated B exposures. A comparison of estimated daily B exposure levels and measured B blood levels confirms the preference of biomonitoring data for a comparison of human field studies. In general, it appears that high environmental exposures to B are lower than possible high occupational exposures. The comparison reveals no contradiction between human and experimental reproductive toxicity data. It clearly appears that human B exposures, even in the highest exposed cohorts, are too low to reach the blood (and target tissue) concentrations that would be required to exert adverse effects on reproductive functions.

Excess dietary cholesterol may have an adverse effect on growth performance of early post-larval Litopenaeus vannamei

PubMed Central

2012-01-01

One experiment was conducted to determine the nutritive value of cholesterol for post-larval shrimp, Litopenaeus vannamei. Four isoenergetic and isonitrogenous diets supplemented with four levels of cholesterol (D1, D2, D3 and D4 with 0, 0.5%, 1% and 2% cholesterol, respectively) were fed to triplicate groups of L. vannamei shrimp (mean initial wet weight 0.8 mg) for 27 days. After the trial, shrimp fed the D1 diet had the best growth performance (final body weights: FBW; weight gain: WG; specific growth rate: SGR), while there was no significant difference between diet treatments with respect to survival. The whole body crude protein level in the shrimp decreased with the increase in dietary cholesterol levels, while the whole body crude lipid level in shrimps in the D4 diet treatment was significantly higher (P < 0.05) than in other diet treatments. Dietary analysis indicated that the D1 diet contained 0.92% cholesterol prior to supplementation, which may have satisfied the dietary cholesterol requirement of post-larval L. vannamei; excess dietary cholesterol may thus lead to adverse effects on the growth performance of post-larval shrimp. PMID:22958647

ANALYSES OF NEUROBEHAVIORAL SCREENING DATA: BENCHMARK DOSE ESTIMATION.

EPA Science Inventory

Analysis of neurotoxicological screening data such as those of the functional observational battery (FOB) traditionally relies on analysis of variance (ANOVA) with repeated measurements, followed by determination of a no-adverse-effect level (NOAEL). The US EPA has proposed the ...

Air Pollution Exposure Model for Individuals (EMI) in Health Studies

EPA Science Inventory

In health studies, traffic-related air pollution is associated with adverse respiratory effects. Due to cost and participant burden of personal measurements, health studies often estimate exposures using local ambient air monitors. Since outdoor levels do not necessarily reflect ...

Tolerability of High-dose Baclofen in the Treatment of Patients with Alcohol Disorders: A Retrospective Study.

PubMed

Rigal, Laurent; Legay Hoang, Léa; Alexandre-Dubroeucq, Constance; Pinot, Juliette; Le Jeunne, Claire; Jaury, Philippe

2015-09-01

The aim of this study was to describe the tolerability of high-dose baclofen taken by patients with alcohol disorders during their first year of treatment. The medical records of all patients prescribed baclofen by one general practitioner were examined and all patients who could be contacted were retrospectively interviewed about adverse effects. Of the 146 eligible patients, 116 (79%) could be interviewed. Ninety (78%) reported at least one adverse effect (mean number per patient: 2.8 ± 2.7). The mean dosage of baclofen at the onset of the first adverse effect was 83 ± 57 mg/day. The most frequent group of adverse effects involved disruption of the wake-sleep cycle and affected 73 patients (63%). Persistent adverse effects occurred in 62 patients (53%). Eight patients (7%) had adverse effects that led them to stop taking baclofen. Their dosages were <90 mg/day at that time. Alertness disorders and depression were the adverse effects that most frequently led to stopping baclofen. Bouts of somnolence and hypomanic episodes were the most potentially dangerous adverse effects. Women reported significantly more adverse effects than men. High-dose baclofen exposes patients with alcohol disorders to many adverse effects. Generally persistent, some adverse effects appear at low doses and may be dangerous. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

PubMed

Sakaida, Isao; Terai, Shuji; Kurosaki, Masayuki; Yasuda, Moriyoshi; Okada, Mitsuru; Bando, Kosuke; Fukuta, Yasuhiko

2017-10-01

Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%). In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained. © 2016 The Japan Society of Hepatology.

Chosen risk level during car-following in adverse weather conditions.

PubMed

Hjelkrem, Odd André; Ryeng, Eirin Olaussen

2016-10-01

This study examines how precipitation, light conditions and surface conditions affect the drivers' risk perception. An indicator CRI (Chosen Risk Index) is defined, which describes the chosen risk level for drivers in a car-following situation. The dataset contains about 70 000 observations of driver behaviour and weather status on a rural road. Based on the theory of risk homeostasis and an assumption that driving behaviour in situations with daylight, dry road and no precipitation reflects drivers' target level of risk, generalised linear models (GLM) were estimated for cars and trucks separately to reveal the effect of adverse weather conditions on risk perception. The analyses show that both car and truck drivers perceive the highest risk when driving on snow covered roads. For car drivers, a snow covered road in combination with moderate rain or light snow are the factors which lowers the CRI the most. For trucks, snow cover and partially covered roads significantly lowers the CRI, while precipitation did not seem to impose any higher risk. Interaction effects were found for car drivers only. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human-relevant Levels of Added Sugar Consumption Increase Female Mortality and Lower Male Fitness in Mice

PubMed Central

Ruff, James S.; Suchy, Amanda K.; Hugentobler, Sara A.; Sosa, Mirtha M.; Schwartz, Bradley L.; Morrison, Linda C.; Gieng, Sin H.; Shigenaga, Mark K.; Potts, Wayne K.

2013-01-01

Consumption of added sugar has increased over recent decades and is correlated with numerous diseases. Rodent models have elucidated mechanisms of toxicity, but only at concentrations beyond typical human exposure. Here we show that comparatively low levels of added sugar consumption have substantial negative effects on mouse survival, competitive ability, and reproduction. Using Organismal Performance Assays (OPAs) – in which mice fed human-relevant concentrations of added sugar (25% Kcal from a mixture of fructose and glucose [F/G]) and control mice compete in seminatural enclosures for territories, resources and mates – we demonstrate that F/G-fed females experience a two-fold increase in mortality while F/G-fed males control 26% fewer territories and produce 25% less offspring. These findings represent the lowest level of sugar consumption shown to adversely affect mammalian health. Clinical defects of F/G-fed mice were decreased glucose clearance and increased fasting cholesterol. Our data highlight that physiological adversity can exist when clinical disruptions are minor, and suggest that OPAs represent a promising technique for unmasking negative effects of toxicants. PMID:23941916

The effects of heat and massage application on autonomic nervous system.

PubMed

Lee, Young-Hee; Park, Bit Na Ri; Kim, Sung Hoon

2011-11-01

The objective of this study is to evaluate the effects of heat and massage application on autonomic nervous system. One hundred thirty-nine subjects volunteered and completed this study. Heat and massage was daily applied for 40 minutes, 5 days a week for 2 weeks. Primary-dependent measures included heart rate variability, sympathetic skin response, and serum cortisol and norepinephrine levels. Serum cortisol levels were significantly decreased at 2 weeks compared to baseline (p=0.003). Plasma norepinephrine levels at 4 weeks were significantly decreased compared to baseline (p=0.010). Heart rate, using the power spectra, increased significantly after 2 weeks compared to baseline. Of autonomic nerve conduction measures, latency was significantly increased at 2 and 4 weeks compared to baseline (p=0.023, 0.012), and amplitude was significantly decreased at 4 weeks compared to baseline (p=0.008). There were no serious adverse events such as burns or other major complications. The results of this study suggest that heat and massage applications provide relaxation to the autonomic nervous system without serious adverse events.

Effects of hospital generic drug substitution on diabetes therapy

PubMed Central

Chen, Hui-Yin; Chang, Hui-Ru; Lang, Hui-Chu

2014-01-01

Objectives To evaluate the effects on physicians’ prescribing behavior and on the therapeutic outcome of non-insulin-dependent diabetes patients of substituting different generic brands of metformin. Methods We adopt a retrospective cohort study involving 280 type-2 diabetes patients who regularly used the outpatient services of one medical center and who had changed metformin brands five times between 2003 and 2008. The aim was to examine the effects of switching brands. The generalized estimating equation was used to determine whether drug brand switching affected patient glycated hemoglobin A1c (HbA1c) levels, their prescribed daily dose, or their adherence to medication with metformin. Results HbA1c levels increased from 7.91 to 8.34 throughout the study period, although it was found that brand switching did not adversely affect HbA1c levels after controlling for patient characteristics and the time course of the study. Furthermore, the prescribed daily dose of metformin was stable throughout the study period, and was approximately 0.8 of the defined daily dose. Finally, although adherence was significantly higher with the original metformin than with the four generic brands, patients still maintained high levels of adherence of >0.8. Conclusion Although switching between different brands of metformin slightly affected the prescribing behavior of the physicians, there was no unfavorable effect on patient HbA1c levels. Thus, the policy of substituting between different generic brands of metformin is a good cost-effective approach that does not adversely affect the quality of diabetes patient care. PMID:24511228

Balneotherapy (or spa therapy) for rheumatoid arthritis.

PubMed

Verhagen, Arianne P; Bierma-Zeinstra, Sita M A; Boers, Maarten; Cardoso, Jefferson R; Lambeck, Johan; de Bie, Rob; de Vet, Henrica C W

2015-04-11

No cure for rheumatoid arthritis (RA) is known at present, so treatment often focuses on management of symptoms such as pain, stiffness and mobility. Treatment options include pharmacological interventions, physical therapy treatments and balneotherapy. Balneotherapy is defined as bathing in natural mineral or thermal waters (e.g. mineral baths, sulphur baths, Dead Sea baths), using mudpacks or doing both. Despite its popularity, reported scientific evidence for the effectiveness or efficacy of balneotherapy is sparse. This review, which evaluates the effects of balneotherapy in patients with RA, is an update of a Cochrane review first published in 2003 and updated in 2008. To perform a systematic review on the benefits and harms of balneotherapy in patients with RA in terms of pain, improvement, disability, tender joints, swollen joints and adverse events. We searched the Cochrane 'Rehabilitation and Related Therapies' Field Register (to December 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1), MEDLIINE (1950 to December 2014), EMBASE (1988 to December 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to December 2014), the Allied and Complementary Medicine Database (AMED) (1985 to December 2014), PsycINFO (1806 to December 2014) and the Physiotherapy Evidence Database (PEDro). We applied no language restrictions; however, studies not reported in English, Dutch, Danish, Swedish, Norwegian, German or French are awaiting assessment. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing and recently completed trials. Studies were eligible if they were randomised controlled trials (RCTs) consisting of participants with definitive or classical RA as defined by the American Rheumatism Association (ARA) criteria of 1958, the ARA/American College of Rheumatology (ACR) criteria of 1988 or the ACR/European League Against Rheumatism (EULAR) criteria of 2010, or by studies using the criteria of Steinbrocker.Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention.The World Health Organization (WHO) and the International League Against Rheumatism (ILAR) determined in 1992 a core set of eight endpoints in clinical trials concerning patients with RA. We considered pain, improvement, disability, tender joints, swollen joints and adverse events among the main outcome measures. We excluded studies when only laboratory variables were reported as outcome measures. Two review authors independently selected trials, performed data extraction and assessed risk of bias. We resolved disagreements by consensus and, if necessary, by third party adjudication. This review includes two new studies and a total of nine studies involving 579 participants. Unfortunately, most studies showed an unclear risk of bias in most domains. Four out of nine studies did not contribute to the analysis, as they presented no data.One study involving 45 participants with hand RA compared mudpacks versus placebo. We found no statistically significant differences in terms of pain on a 0 to 100-mm visual analogue scale (VAS) (mean difference (MD) 0.50, 95% confidence interval (CI) -0.84 to 1.84), improvement (risk ratio (RR) 0.96, 95% CI 0.54 to 1.70) or number of swollen joints on a scale from 0 to 28 (MD 0.60, 95% CI -0.90 to 2.10) (very low level of evidence). We found a very low level of evidence of reduction in the number of tender joints on a scale from 0 to 28 (MD -4.60, 95% CI -8.72 to -0.48; 16% absolute difference). We reported no physical disability and presented no data on withdrawals due to adverse events or on serious adverse events.Two studies involving 194 participants with RA evaluated the effectiveness of additional radon in carbon dioxide baths. We found no statistically significant differences between groups for all outcomes at three-month follow-up (low to moderate level of evidence). We noted some benefit of additional radon at six months in terms of pain frequency (RR 0.6, 95% CI 0.4 to 0.9; 31% reduction; improvement in one or more points (categories) on a 4-point scale; moderate level of evidence) and 9.6% reduction in pain intensity on a 0 to 100-mm VAS (MD 9.6 mm, 95% CI 1.6 to 17.6; moderate level of evidence). We also observed some benefit in one study including 60 participants in terms of improvement in one or more categories based on a 4-point scale (RR 2.3, 95% CI 1.1 to 4.7; 30% absolute difference; low level of evidence). Study authors did not report physical disability, tender joints, swollen joints, withdrawals due to adverse events or serious adverse events.One study involving 148 participants with RA compared balneotherapy (seated immersion) versus hydrotherapy (exercises in water), land exercises or relaxation therapy. We found no statistically significant differences in pain on the McGill Questionnaire or in physical disability (very low level of evidence) between balneotherapy and the other interventions. No data on improvement, tender joints, swollen joints, withdrawals due to adverse events or serious adverse events were presented.One study involving 57 participants with RA evaluated the effectiveness of mineral baths (balneotherapy) versus Cyclosporin A. We found no statistically significant differences in pain intensity on a 0 to 100-mm VAS (MD 9.64, 95% CI -1.66 to 20.94; low level of evidence) at 8 weeks (absolute difference 10%). We found some benefit of balneotherapy in overall improvement on a 5-point scale at eight weeks of 54% (RR 2.35, 95% CI 1.44 to 3.83). We found no statistically significant differences (low level of evidence) in the number of swollen joints, but some benefit of Cyclosporin A in the number of tender joints (MD 8.9, 95% CI 3.8 to 14; very low level of evidence). Physical disability, withdrawals due to adverse events and serious adverse events were not reported. Overall evidence is insufficient to show that balneotherapy is more effective than no treatment, that one type of bath is more effective than another or that one type of bath is more effective than mudpacks, exercise or relaxation therapy.

[ANTHROPOMETRIC INDICATORS AND CARDIOMETABOLIC EVENTS AMONG SCHOOL-AGED CHILDREN FROM SONORA, MEXICO].

PubMed

Peralta Peña, Sandra Lidia; Reséndiz González, Eunice; Rubí Vargas, María; Terrazas Medina, Efraín Alonso; Cupul Uicab, Lea Aurora

2015-10-01

obesity in childhood is predictive of obesity in adulthood and it is associated with adverse health effect apparent since childhood; however, the joint assessment of obesity and adverse events among children in clinical settings is unusual. to assess the association of overweight and obesity, abdominal obesity, and excess body fat with systolic [SBP] and diastolic [DBP] blood pressure, lipid profile and glucose levels; and to identify the best anthropometric indicator of such events. we conducted a cross-sectional study in a sample of 412 schoolchildren. The presence of overweight and obesity, abdominal obesity and excess body fat was determined among all participants; levels of total cholesterol, triglycerides, high and low density lipoproteins, and glucose were measured in a subsample (n = 133). The associations of interest were assessed using adjusted linear and logistic regression models. 33% of the children were overweight or obese. Overall, overweight, obesity, abdominal obesity, and excess body fat were associated with elevated SBP and DBP and with a lipid profile and glucose levels that could indicate health risks among these children. Overweight and obesity were the best predictors of such events. among these school-aged children, we observed that obesity was associated with high odds of having adverse health outcomes such as high blood pressure, lipids and glucose. Such adverse events can be predicted by the presence of obesity measured by BMI, which is a noninvasive, inexpensive and easy to implement measure. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Molecular Effects of Neonicotinoids in Honey Bees (Apis mellifera).

PubMed

Christen, Verena; Mittner, Fabian; Fent, Karl

2016-04-05

Neonicotinoids are implicated in the decline of bee populations. As agonists of nicotinic acetylcholine receptors, they disturb acetylcholine receptor signaling leading to neurotoxicity. Several behavioral studies showed the link between neonicotinoid exposure and adverse effects on foraging activity and reproduction. However, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic levels of three neonicotinoids and nicotine, and compared laboratory studies to field exposures with acetamiprid. We assessed transcriptional alterations of eight selected genes in caged honey bees exposed to different concentrations of the neonicotinoids acetamiprid, clothianidin, imidacloporid, and thiamethoxam, as well as nicotine. We determined transcripts of several targets, including nicotinic acetylcholine receptor α 1 and α 2 subunit, the multifunctional gene vitellogenin, immune system genes apidaecin and defensin-1, stress-related gene catalase and two genes linked to memory formation, pka and creb. Vitellogenin showed a strong increase upon neonicotinoid exposures in the laboratory and field, while creb and pka transcripts were down-regulated. The induction of vitellogenin suggests adverse effects on foraging activity, whereas creb and pka down-regulation may be implicated in decreased long-term memory formation. Transcriptional alterations occurred at environmental concentrations and provide an explanation for the molecular basis of observed adverse effects of neonicotinoids to bees.

Driving monotonous routes in a train simulator: the effect of task demand on driving performance and subjective experience.

PubMed

Dunn, Naomi; Williamson, Ann

2012-01-01

Although monotony is widely recognised as being detrimental to performance, its occurrence and effects are not yet well understood. This is despite the fact that task-related characteristics, such as monotony and low task demand, have been shown to contribute to performance decrements over time. Participants completed one of two simulated train-driving scenarios. Both were highly monotonous and differed only in terms of the level of cognitive demand required (i.e. low demand or high demand). These results highlight the seriously detrimental effects of the combination of monotony and low task demands and clearly show that even a relatively minor increase in cognitive demand can mitigate adverse monotony-related effects on performance for extended periods of time. Monotony is an inherent characteristic of transport industries, including rail, aviation and road transport, which can have adverse impact on safety, reliability and efficiency. This study highlights possible strategies for mitigating these adverse effects. Practitioner Summary: This study provides evidence for the importance of cognitive demand in mitigating monotony-related effects on performance. The results have clear implications for the rapid onset of performance deterioration in low demand monotonous tasks and demonstrate that these detrimental performance effects can be overcome with simple solutions, such as making the task more cognitively engaging.

Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation.

PubMed

Gur, Serap; Kadowitz, Philip J; Hellstrom, Wayne Jg

2013-01-01

Treatment with 5-alpha reductase inhibitors (5ARI) is commonly utilized for the treatment of benign prostatic hyperplasia (BPH). The true prevalence of sexual side effects with 5ARI treatment is currently unknown. The current article reviews the reported adverse effects of 5ARI in regard to erectile function, sexual desire and ejaculation. A PubMed search was performed of all articles from 1990 to present, which reported any sexual side effects with finasteride or dutasteride. Preference was given to more recent and human studies where available. Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5 - 9%. Decreased circulating dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARI. Patients receiving therapy with 5ARI should be counseled as to potential sexual and psychological adverse effects. Future clinical studies are needed to further investigate the sexual side effects associated with this class of drugs.

[Synthesis and physico-chemical characterisation of some new derivatives of rutoside and clofibric acid].

PubMed

Lupaşcu, D; Profire, Lenuţa; Dănilă, Gh

2006-01-01

Fibrates are drugs with efficacy in reducing blood cholesterol levels and especially, triglyceride plasma levels. Unfortunately, fibrates have a poor water-solubility and showed some adverse reactions at long treatment. The objective of this study was to obtain some new clofibric acid derivatives with rutin; some of these compounds contain a guanidine moiety, known as effective at cardiovascular level. All the compounds are soluble in water.

Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.

PubMed

Meaney, Calvin J; Arabi, Ziad; Venuto, Rocco C; Consiglio, Joseph D; Wilding, Gregory E; Tornatore, Kathleen M

2014-06-12

After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy. The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation. A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse effects (p=0.008) in renal transplant recipients receiving tacrolimus and mycophenolic acid compared to the cyclosporine regimen. This finding demonstrated construct validity. Intra-class correlation was 0.81 (95% confidence interval: 0.65-0.90) and Kappa statistic of 0.68 ± 0.25 for all 18 adverse effects and verified substantial inter-rater reliability. This immunosuppressive adverse effects scoring system in stable renal transplant recipients was evaluated and substantiated face, content and construct validity with inter-rater reliability. The scoring system may facilitate prospective, standardized clinical monitoring of immunosuppressive adverse drug effects in stable renal transplant recipients and improve medication adherence.

Effects of consanguineous marriage on reproductive behaviour, adverse pregnancy outcomes and offspring mortality in Oman.

PubMed

Islam, M Mazharul

2013-05-01

The long tradition of high prevalence of consanguineous marriages in Omani society may have ramifications for reproductive behaviour and health of offspring. To examine the relevance of consanguinity to reproductive behaviour, adverse pregnancy outcome and offspring mortality in Oman. The data analysed came from the 2000 Oman National Health Survey. Selected indicators that are related to reproductive behaviour, adverse pregnancy outcome and offspring mortality were considered as explanatory variables. Various statistical methods and tests were used for data analysis. Consanguineous marriage was found to be associated with lower age at first birth, higher preference for larger family size, lower level of husband-wife communication about use of family planning methods and lower rate of contraceptive use. Although bivariate analysis showed elevated fertility and childhood mortality among the women with consanguineous marriage, after controlling for relevant socio-demographic factors in multivariate analysis, fertility, childhood mortality and foetal loss showed no significant association with consanguinity in Oman. Consanguinity plays an important role in determining some of the aspects of reproduction and health of newborns, but did not show any detrimental effects on fertility and offspring mortality. The high level of consanguinity and its relevance to reproduction in Oman need to be considered in its public health strategy in a culturally acceptable manner.

The application of high-pressure treatment in the reduction of salt levels in reduced-phosphate breakfast sausages.

PubMed

O'Flynn, Claire C; Cruz-Romero, Malco C; Troy, Declan; Mullen, Anne M; Kerry, Joe P

2014-03-01

This study investigated the effects of high pressure (HP) treatment of pork meat before manufacturing sausages with reduced salt levels and compared them to sausages manufactured with untreated meat (control sausages). A 2×5 factorial design was set up incorporating two pressure levels (0 or 150 MPa) and five salt levels (0.5, 1.0, 1.5, 2.0 and 2.5%). Most quality attributes were affected when salt levels were reduced below 1.5%. Fat loss (FL) was (P<0.05) affected by salt level; samples with <1.5% salt had the highest FL. HP treatment increased emulsion stability and reduced cook loss (CL) compared to control sausages. Increased CL was observed when salt was reduced below 2.0%. Salt reduction below 1.5% adversely affected colour, sensory and texture attributes. Independent of salt, HP treatment affected adversely juiciness and cohesiveness while adhesiveness was improved. Overall, there is potential to manufacture sausages maintaining organoleptic and functional properties traditionally associated with sausages using HP treated meat. Copyright © 2013 Elsevier Ltd. All rights reserved.

Family Adversity, Positive Peer Relationships, and Children's Externalizing Behavior: A Longitudinal Perspective on Risk and Resilience

PubMed Central

Criss, Michael M.; Pettit, Gregory S.; Bates, John E.; Dodge, Kenneth A.; Lapp, Amie L.

2009-01-01

Peer acceptance and friendships were examined as moderators in the link between family adversity and child externalizing behavioral problems. Data on family adversity (i.e., ecological disadvantage, violent marital conflict, and harsh discipline) and child temperament and social information processing were collected during home visits from 585 families with 5-year-old children. Children's peer acceptance, friendship, and friends' aggressiveness were assessed with sociometric methods in kindergarten and grade 1. Teachers provided ratings of children's externalizing behavior problems in grade 2. Peer acceptance served as a moderator for all three measures of family adversity, and friendship served as a moderator for harsh discipline. Examination of regression slopes indicated that family adversity was not significantly associated with child externalizing behavior at high levels of positive peer relationships. These moderating effects generally were not qualified by child gender, ethnicity, or friends' aggressiveness, nor were they accounted for by child temperament or social information-processing patterns. The need for process-oriented studies of risk and protective factors is stressed. PMID:12146744

Childhood adversity and traumatic exposures during deployment as predictors of mental health in Australian military veterans.

PubMed

Zheng, Wu Yi; Kanesarajah, Jeeva; Waller, Michael; McGuire, Annabel C; Treloar, Susan A; Dobson, Annette J

2016-02-01

To examine whether the relationship between traumatic exposure on deployment and poor mental health varies by the reported level of childhood adversity experienced in Australian military veterans deployed to the Bougainville or East Timor military operations. Cross-sectional self-reported survey data were collected in 2008 from 3,564 Australian military veterans who deployed to East Timor or Bougainville on their deployment experiences, health and recall of childhood events. Multivariable logistic regression was used to investigate the association between childhood adversity, deployment exposures and mental health. The most common childhood adversity reported was 'not having a special teacher, youth worker or family friend who looked out for them while growing up'. On average, responders reported experiencing 3.5 adverse childhood experiences (SD 2.7) and averaged 5.3 (SD 4.9) traumatic exposures on deployment. Both childhood adversity and traumatic exposures on deployment were associated with higher odds of poorer mental health. However, there was no evidence that level of childhood adversity modified the association between traumatic exposure and mental health. These findings suggest that military personnel who recalled a higher level of childhood adversity may need to be monitored for poor mental health and, if required, provided with appropriate support. © 2015 Public Health Association of Australia.

Toxicity of inhaled traffic related particulate matter

NASA Astrophysics Data System (ADS)

Gerlofs-Nijland, Miriam E.; Campbell, Arezoo; Miller, Mark R.; Newby, David E.; Cassee, Flemming R.

2009-02-01

Traffic generated ultrafine particulates may play a major role in the development of adverse health effects. However, little is known about harmful effects caused by recurring exposure. We hypothesized that repeated exposure to particulate matter results in adverse pulmonary and systemic toxic effects. Exposure to diesel engine exhaust resulted in signs of oxidative stress in the lung, impaired coagulation, and changes in the immune system. Pro-inflammatory cytokine levels were decreased in some regions of the brain but increased in the striatum implying that exposure to diesel engine exhaust may selectively aggravate neurological impairment. Data from these three studies suggest that exposure to traffic related PM can mediate changes in the vasculature and brain of healthy rats. To what extent these changes may contribute to chronic neurodegenerative or vascular diseases is at present unclear.

Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice

PubMed Central

Zhang, Zhaobin; Hu, Ying; Guo, Jilong; Yu, Tong; Sun, Libei; Xiao, Xuan; Zhu, Desheng; Nakanishi, Tsuyoshi; Hiromori, Youhei; Li, Junyu; Fan, Xiaolin; Wan, Yi; Cheng, Siyu; Li, Jun; Guo, Xuan; Hu, Jianying

2017-01-01

Bisphenol A (BPA) is used in the production of plastic but has oestrogenic activity. Therefore, BPA substitutes, such as fluorene-9-bisphenol (BHPF), have been introduced for the production of so-called ‘BPA-free' plastics. Here we show that BHPF is released from commercial ‘BPA-free' plastic bottles into drinking water and has anti-oestrogenic effects in mice. We demonstrate that BHPF has anti-oestrogenic activity in vitro and, in an uterotrophic assay in mice, induces low uterine weight, atrophic endometria and causes adverse pregnancy outcomes, even at doses lower than those of BPA for which no observed adverse effect have been reported. Female mice given water containing BHPF released from plastic bottles, have detectable levels of BHPF in serum, low uterine weights and show decreased expressions of oestrogen-responsive genes. We also detect BHPF in the plasma of 7/100 individuals, who regularly drink water from plastic bottles. Our data suggest that BPA substitutes should be tested for anti-oestrogenic activity and call for further study of the toxicological effects of BHPF on human health. PMID:28248286

Coastal surface sediment quality assessment in Leizhou Peninsula (South China Sea) based on SEM-AVS analysis.

PubMed

Li, Feng; Lin, Jin-qin; Liang, Yan-yan; Gan, Hua-yang; Zeng, Xiang-yun; Duan, Zhi-peng; Liang, Kai; Liu, Xing; Huo, Zhen-hai; Wu, Chang-hua

2014-07-15

Surface sediments from the coastal area of the Leizhou Peninsula in the South China Sea were collected and analyzed and the potential ecological risks in the area were assessed based on acid-volatile sulfide (AVS) model. The AVS levels are between 0.109 and 55.6 μmol g(-1), with the average at 4.45 μmol g(-1). The high AVS-concentration zones include the aquaculture areas of Liusha Bay and the densely populated areas of Zhanjiang Bay. The simultaneously extracted metals (SEM) range from 0.026 μmol g(-1) to 8.61 μmol g(-1), with the average at 0.843 μmol g(-1). Most of high SEM-concentration stations were located in ports or aquaculture zones. Most of the coastal surface sediments of the Leizhou Peninsula (90%) had no adverse biological effects according to the criterion proposed by USEPA (2005); while adverse effects were uncertain in some stations (8%); even in 2 stations (2%) adverse biological effects may be expected. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nebivolol Induced Hyperkalemia: Case Report

PubMed

Altabas, Karmela; Altabas, Velimir; Gulin, Tonko

2016-12-01

In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation. Our patient, a 47-year-old woman taking nebivolol for hypertension developed persistent hyperkalemia, with serum potassium levels up to 6.4 mmol/L. After extensive diagnostic evaluation and exclusion of other known conditions leading to hyperkalemia, its cause remained occult. Since hyperkalemia coincided with increased doses of nebivolol, dose reduction and discontinuation were attempted, resulting in normalized serum potassium. Poor drug metabolism could not explain this adverse effect, since pharmacogenetic testing showed no relevant aberrations. In conclusion, hyperkalemia is a harmful adverse event with possible lethal outcome, and it may be caused by nebivolol. Therefore, medical professionals have to be aware of this side effect and hyperkalemia should be listed as an adverse event in nebivolol SmPC.

SITE SITE DISTURBANCE EFFECTS ON A CLAY SOIL UNDER PINUS RADIATA - ROOT BIOMASS, MYCORRHIZAL COLONISATION, 15AMMONIUM UPTAKE, AND FOLIAR NUTRIENT LEVELS

EPA Science Inventory

Timber harvesting can result in adverse physical, chemical and biological alterations to soil. The objective of this study was to examine the effects of site disturbance to determine the extent and duration of possible harvesting impacts on soil chemical and biological propertie...

The Effects of Poverty on Children's Socioemotional Development: An Ecological Systems Analysis.

ERIC Educational Resources Information Center

Eamon, Mary Keegan

2001-01-01

Bronfenbrenner's process-person-context-time model is used to examine theories that explain adverse effects of economic deprivation on children's socioemotional development. Processes of not only the family, but also those of the peer group and school, and in other levels of the ecological environment may also explain the relation between economic…

Effects of an Early Family Intervention on Children's Memory: The Mediating Effects of Cortisol Levels

ERIC Educational Resources Information Center

Bugental, Daphne Blunt; Schwartz, Alex; Lynch, Colleen

2010-01-01

Developmental psychologists have long been concerned with the ways that early adversity influences children's long-term outcomes. In the current study, activity of the hypothalamic-pituitary-adrenal axis of medically at-risk (e.g., preterm) infants was measured as a result of maternal participation in a novel cognitively based home visitation…

Social Support Buffers the Effects of Terrorism on Adolescent Depression: Findings from Sderot, Israel

ERIC Educational Resources Information Center

Henrich, Christopher C.; Shahar, Golan

2008-01-01

A prospective study of 29 Israeli middle school students experiencing rocket attacks in Sderot, Israel, examined if higher levels of baseline social support acted as a buffer against the adverse psychological effects of terrorism on adolescent depression. Results demonstrate the importance of community mental health efforts to promote family,…

Distribution and Biological Effects of Nanoparticles in the Reproductive System.

PubMed

Liu, Ying; Li, Hongxia; Xiao, Kai

2016-01-01

Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our understanding of biological effects of nanoparticles on the reproductive system.

HAZARD ASSESSMENT OF METALS AND METAL COMPOUNDS IN TERRESTRIAL SYSTEMS

EPA Science Inventory

Metal accumulation in soil can result in adverse effects on soil biota, and may concentrate metals in food chains to levels detrimental to humans and wildlife. A SETAC Pellston Workshop entitled " Hazard Identification Approach For Metals And Inorganic Metal Substances" examined...

A BIOLOGICALLY BASED MODEL FOR THE HORMONAL CONTROL OF THE MENSTRUAL CYCLE

EPA Science Inventory

Recent studies suggest that environmental substances that mimic endogenous estrogens (eg. estradiol) may disrupt the endocrine system. While high-level exposures to estrogenic substances are believed to contribute to such adverse effects as cancer, developmental disorders, and fe...

The effects of low levels of herbicides on simple plant communities

EPA Science Inventory

In the United States, the US Environmental Protection Agency has the responsibility for the registration of pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act. Prior to registration applicants must demonstrate that their product will not adversely affect hu...

CRITICAL HEALTH ISSUES OF CRITERIA AIR POLLUTANTS

EPA Science Inventory

This chapter summarizes the key health information on ubiquitous outdoor air pollutants that can cause adverse health effects at current or historical ambient levels in the United States. Of the thousands of air pollutants, very few meet this definition. The Clean Air Act (CA...

Quantifying the Effects of Pesticide Exposure on Seasonal Fecundity Rates of Birds

EPA Science Inventory

Current risk assessment practice uses the results of avian reproduction tests in risk quotients to classify the potential for pesticide use to adversely affect avian reproductive success. However, as risk assessors move toward better understanding the population-level consequenc...

H295R Human Adrenocortical Carcinoma Cells as a Screening Platform for Steroidogenesis (NC SOT)

EPA Science Inventory

Proper biosynthesis and metabolism of steroid hormones is essential for development and reproduction. Disruption of steroidogenesis by environmental toxicants results in altered hormone levels causing adverse reproductive and developmental effects. H295R human adrenocortical carc...

The association of shift-level nurse staffing with adverse patient events.

PubMed

Patrician, Patricia A; Loan, Lori; McCarthy, Mary; Fridman, Moshe; Donaldson, Nancy; Bingham, Mona; Brosch, Laura R

2011-02-01

The objective of this study was to demonstrate the association between nurse staffing and adverse events at the shift level. Despite a growing body of research linking nurse staffing and patient outcomes, the relationship of staffing to patient falls and medication errors remains equivocal, possibly due to dependence on aggregated data. Thirteen military hospitals participated in creating a longitudinal nursing outcomes database to monitor nurse staffing, patient falls and medication errors, and other outcomes. Unit types were analyzed separately to stratify patient and nurse staffing characteristics. Bayesian hierarchical logistic regression modeling was used to examine associations between staffing and adverse events. RN skill mix, total nursing care hours, and experience, measured by a proxy variable, were associated with shift-level adverse events. Consideration must be given to nurse staffing and experience levels on every shift.

Operation and Maintence, Vermilion Harbor, Erie County, Ohio.

DTIC Science & Technology

1976-03-01

channel and structural maintenance activities at Vermilion Harbor. Although 6 ...- this alternative would eliminate temporary adverse ecological effects of...of dredging on water quality, aquatic ecology , and harbor recreation and related 4 businesses wbuld be reduced to a level commensurate with reduced...effects on aquatic ecology but would have long- term, beneficial effects on shoreline erosion and beach areas. There have been no specific requests from

Serum placental growth factor, vascular endothelial growth factor, soluble vascular endothelial growth factor receptor-1 and -2 levels in periodontal disease, and adverse pregnancy outcomes.

PubMed

Sert, Tuba; Kırzıoğlu, F Yeşim; Fentoğlu, Ozlem; Aylak, Firdevs; Mungan, Tamer

2011-12-01

The aim of this study is the evaluation of levels of serum interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and soluble VEGF receptor (sVEGFR)-1 and -2 in the association between periodontal disease and adverse pregnancy outcomes. One hundred and nine mothers, who recently gave birth, and 51 women who were not recently pregnant, aged 18 to 35 years, were included in this study. The mothers were classified as term birth, preterm birth (PTB), and preterm low birth weight (PLBW) in respect to their gestational age and baby's birth weight. The birth mothers were grouped as having gingivitis or periodontitis. The non-pregnant group also included periodontally healthy patients. Venous blood samples were collected to evaluate serum IL-1β, IL-6, IL-10, TNF-α, VEGF, PIGF, and sVEGFR-1 and -2 levels. Mother's weight, education, and income level were significantly associated with pregnancy outcomes. Serum levels of IL-1β, TNF-α, IL-6, VEGF, and sVEGFR-1 and -2 showed an increase in significance when related to pregnancy. Whereas in the PLBW group IL-1β, VEGF, and sVEGFR-2 levels were increased, in the PTB group sVEGFR-1 levels were increased. Additionally, the patients in the PLBW group with periodontitis had higher serum levels of IL-1β, VEGF, sVEGFR-2, and IL-1β/IL-10. The serum levels of IL-1β, VEGF, and sVEGFR-1 and -2 may have a potential effect on the mechanism of the association between periodontal disease and adverse pregnancy outcomes.

Effects of road traffic noise and the benefit of access to quietness

NASA Astrophysics Data System (ADS)

Öhrström, E.; Skånberg, A.; Svensson, H.; Gidlöf-Gunnarsson, A.

2006-08-01

Socio-acoustic surveys were carried out as part of the Soundscape Support to Health research programme to assess the health effects of various soundscapes in residential areas. The study was designed to test whether having access to a quiet side of one's dwelling enhances opportunities for relaxation and reduces noise annoyance and other adverse health effects related to noise. The dwellings chosen were exposed to sound levels from road traffic ranging from about L=45-68 dB at the most-exposed side. The study involved 956 individuals aged 18-75 years. The results demonstrate that access to quiet indoor and outdoor sections of one's dwelling supports health; it produces a lower degree and extent of annoyance and disturbed daytime relaxation, improves sleep and contributes to physiological and psychological well-being. Having access to a quiet side of one's dwelling reduces disturbances by an average of 30-50% for the various critical effects, and corresponds to a reduction in sound levels of ( LAeq,24h) 5 dB at the most-exposed side. To protect most people (80%) from annoyance and other adverse effects, sound levels from road traffic should not exceed ( LAeq,24h) 60 dB at the most-exposed side, even if there is access to a quiet side of one's dwelling ( LAeq,24h⩽45 dB).

Adverse health effects due to arsenic exposure: modification by dietary supplementation of jaggery in mice.

PubMed

Singh, Nrashant; Kumar, D; Lal, Kewal; Raisuddin, S; Sahu, Anand P

2010-02-01

Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic. Copyright 2009 Elsevier Inc. All rights reserved.

Estimating the Potential Impact of Tobacco Control Policies on Adverse Maternal and Child Health Outcomes in the United States Using the SimSmoke Tobacco Control Policy Simulation Model.

PubMed

Levy, David; Mohlman, Mary Katherine; Zhang, Yian

2016-05-01

Numerous studies document the causal relationship between prenatal smoking and adverse maternal and child health (MCH) outcomes. Studies also reveal the impact that tobacco control policies have on prenatal smoking. The purpose of this study is to estimate the effect of tobacco control policies on prenatal smoking prevalence and adverse MCH outcomes. The US SimSmoke simulation model was extended to consider adverse MCH outcomes. The model estimates prenatal smoking prevalence and, applying standard attribution methods, uses estimates of MCH prevalence and relative smoking risks to estimate smoking-attributable MCH outcomes over time. The model then estimates the effect of tobacco control policies on adverse birth outcomes averted. Different tobacco control policies have varying impacts on the number of smoking-attributable adverse MCH birth outcomes. Higher cigarette taxes and comprehensive marketing bans individually have the biggest impact with a 5% to 10% reduction across all outcomes for the period from 2015 to 2065. The policies with the lowest impact (2%-3% decrease) during this period are cessation treatment, health warnings, and complete smoke-free laws. Combinations of all policies with each tax level lead to 23% to 28% decreases across all outcomes. Our findings demonstrate the substantial impact of strong tobacco control policies for preventing adverse MCH outcomes, including long-term health implications for children exposed to low birth weight and preterm birth. These benefits are often overlooked in discussions of tobacco control. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory.

PubMed

Levens, Sara M; Armstrong, Laura Marie; Orejuela-Dávila, Ana I; Alverio, Tabitha

2017-09-01

Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity.

Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials

PubMed Central

Derry, Sheena; Kong Loke, Yoon; Aronson, Jeffrey K

2001-01-01

Background We would expect information on adverse drug reactions in randomised clinical trials to be easily retrievable from specific searches of electronic databases. However, complete retrieval of such information may not be straightforward, for two reasons. First, not all clinical drug trials provide data on the frequency of adverse effects. Secondly, not all electronic records of trials include terms in the abstract or indexing fields that enable us to select those with adverse effects data. We have determined how often automated search methods, using indexing terms and/or textwords in the title or abstract, would fail to retrieve trials with adverse effects data. Methods We used a sample set of 107 trials known to report frequencies of adverse drug effects, and measured the proportion that (i) were not assigned the appropriate adverse effects indexing terms in the electronic databases, and (ii) did not contain identifiable adverse effects textwords in the title or abstract. Results Of the 81 trials with records on both MEDLINE and EMBASE, 25 were not indexed for adverse effects in either database. Twenty-six trials were indexed in one database but not the other. Only 66 of the 107 trials reporting adverse effects data mentioned this in the abstract or title of the paper. Simultaneous use of textword and indexing terms retrieved only 82/107 (77%) papers. Conclusions Specific search strategies based on adverse effects textwords and indexing terms will fail to identify nearly a quarter of trials that report on the rate of drug adverse effects. PMID:11591220

The effect of age and comedication on lamotrigine clearance, tolerability, and efficacy.

PubMed

Arif, Hiba; Svoronos, Alexandra; Resor, Stanley R; Buchsbaum, Richard; Hirsch, Lawrence J

2011-10-01

To compare pharmacokinetics, tolerability, and efficacy of lamotrigine (LTG) in older versus younger adults. We studied 686 adult outpatients seen at our center over 5 years. We compared apparent clearance (CL) of LTG in the youngest (16-36 years; n = 247) and oldest (55-92 years; n = 155) tertiles. We analyzed one-year retention for younger and older adults newly started on LTG, frequency of adverse effects causing intolerability, and rates of specific adverse effects. We also investigated 6-month seizure freedom. Median LTG CL of older adults taking LTG in monotherapy was approximately 22% lower compared to younger adults (28.8 vs. 36.5 ml/h/kg; p < 0.001). LTG CL in older adults was lower compared to younger adults in patients on polytherapy and on polytherapy without enzyme inducers or valproate. One-year retention for LTG was comparable in older (78.1%, 121/155) and younger (72.4%, 179/247) adults. Intolerability to LTG was higher in older (34.8%) versus younger adults (24.2%; p = 0.005). Imbalance, drowsiness, and dizziness were common intolerable side effects in both groups. Older patients had higher rates of intolerability due to imbalance (16% vs. 4%), drowsiness (13% vs. 7%), and tremor (5% vs. 2%) compared with younger patients. Rates of 6-month seizure freedom were comparable, and small numbers of each group benefited from very high levels of LTG (>15 μg/ml). LTG CL in monotherapy in older adults is approximately 20% lower than in younger adults. For a given serum LTG level, older adults are twice as likely to have significant adverse effects compared to younger adults. Older patients are more likely to experience imbalance, drowsiness, and tremor than younger patients. Younger adults tolerate LTG better than older adults, but one-year retention is comparable. Some patients may benefit from high serum levels of LTG. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Relevance of risk predictions derived from a chronic species sensitivity distribution with cadmium to aquatic populations and ecosystems

USGS Publications Warehouse

Mebane, C.A.

2010-01-01

Criteria to protect aquatic life are intended to protect diverse ecosystems, but in practice are usually developed from compilations of single-species toxicity tests using standard test organisms that were tested in laboratory environments. Species sensitivity distributions (SSDs) developed from these compilations are extrapolated to set aquatic ecosystem criteria. The protectiveness of the approach was critically reviewed with a chronic SSD for cadmium comprising 27 species within 21 genera. Within the data set, one genus had lower cadmium effects concentrations than the SSD fifth percentile-based criterion, so in theory this genus, the amphipod Hyalella, could be lost or at least allowed some level of harm by this criteria approach. However, population matrix modeling projected only slightly increased extinction risks for a temperate Hyalella population under scenarios similar to the SSD fifth percentile criterion. The criterion value was further compared to cadmium effects concentrations in ecosystem experiments and field studies. Generally, few adverse effects were inferred from ecosystem experiments at concentrations less than the SSD fifth percentile criterion. Exceptions were behavioral impairments in simplified food web studies. No adverse effects were apparent in field studies under conditions that seldom exceeded the criterion. At concentrations greater than the SSD fifth percentile, the magnitudes of adverse effects in the field studies were roughly proportional to the laboratory-based fraction of species with adverse effects in the SSD. Overall, the modeling and field validation comparisons of the chronic criterion values generally supported the relevance and protectiveness of the SSD fifth percentile approach with cadmium. ?? 2009 Society for Risk Analysis.

Exposure to medium and high ambient levels of ozone causes adverse systemic inflammatory and cardiac autonomic effects

PubMed Central

Wong, Hofer; Donde, Aneesh; Frelinger, Jessica; Dalton, Sarah; Ching, Wendy; Power, Karron; Balmes, John R.

2015-01-01

Epidemiological evidence suggests that exposure to ozone increases cardiovascular morbidity. However, the specific biological mechanisms mediating ozone-associated cardiovascular effects are unknown. To determine whether short-term exposure to ambient levels of ozone causes changes in biomarkers of cardiovascular disease including heart rate variability (HRV), systemic inflammation, and coagulability, 26 subjects were exposed to 0, 100, and 200 ppb ozone in random order for 4 h with intermittent exercise. HRV was measured and blood samples were obtained immediately before (0 h), immediately after (4 h), and 20 h after (24 h) each exposure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 20 h after exposure. Regression modeling was used to examine dose-response trends between the endpoints and ozone exposure. Inhalation of ozone induced dose-dependent adverse changes in the frequency domains of HRV across exposures consistent with increased sympathetic tone [increase of (parameter estimate ± SE) 0.4 ± 0.2 and 0.3 ± 0.1 in low- to high-frequency domain HRV ratio per 100 ppb increase in ozone at 4 h and 24 h, respectively (P = 0.02 and P = 0.01)] and a dose-dependent increase in serum C-reactive protein (CRP) across exposures at 24 h [increase of 0.61 ± 0.24 mg/l in CRP per 100 ppb increase in ozone (P = 0.01)]. Changes in HRV and CRP did not correlate with ozone-induced local lung inflammatory responses (BAL granulocytes, IL-6, or IL-8), but changes in HRV and CRP were associated with each other after adjustment for age and ozone level. Inhalation of ozone causes adverse systemic inflammatory and cardiac autonomic effects that may contribute to the cardiovascular mortality associated with short-term exposure. PMID:25862833

A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.

PubMed

Wolff, Andy; Joshi, Revan Kumar; Ekström, Jörgen; Aframian, Doron; Pedersen, Anne Marie Lynge; Proctor, Gordon; Narayana, Nagamani; Villa, Alessandro; Sia, Ying Wai; Aliko, Ardita; McGowan, Richard; Kerr, Alexander Ross; Jensen, Siri Beier; Vissink, Arjan; Dawes, Colin

2017-03-01

Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.

Impact of time to return of spontaneous circulation on neuroprotective effect of targeted temperature management at 33 or 36 degrees in comatose survivors of out-of hospital cardiac arrest.

PubMed

Kjaergaard, Jesper; Nielsen, Niklas; Winther-Jensen, Matilde; Wanscher, Michael; Pellis, Tommaso; Kuiper, Michael; Hartvig Thomsen, Jakob; Wetterslev, Jørn; Cronberg, Tobias; Bro-Jeppesen, John; Erlinge, David; Friberg, Hans; Søholm, Helle; Gasche, Yvan; Horn, Janneke; Hovdenes, Jan; Stammet, Pascal; Wise, Matthew P; Åneman, Anders; Hassager, Christian

2015-11-01

Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC. In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days. Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM. Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of new chlorhexidine- and cetylpyridinium chloride-based mouthrinse formulations adjunctive to scaling and root planing: pilot study.

PubMed

García-Gargallo, M; Zurlohe, M; Montero, E; Alonso, B; Serrano, J; Sanz, M; Herrera, D

2017-11-01

To compare the effect of two newly formulated chlorhexidine (CHX) and cetylpyridinium chloride (CPC) mouthrinses after scaling and root planing (SRP) in terms of clinical, microbiological, patient-based variables and adverse events, with a positive control with the same active components, already marketed and tested. A pilot, randomized clinical trial, double-blind, parallel design with 1-month follow-up was conducted. Chronic periodontitis patients requiring non-surgical periodontal therapy were enrolled and randomly assigned to: (i) SRP and test-1 (new reformulation: 0.12% CHX and 0.05% CPC); (ii) SRP and test-2 (new formulation: 0.03% CHX and 0.05% CPC); or (iii) SRP and positive control (commercial product: 0.12% CHX and 0.05% CPC). All variables were evaluated at baseline and 1 month after SRP. Quantitative variables were compared by means of anova or Kruskal-Wallis test and qualitative variables by chi-square or McNemar tests. Thirty patients (10 per group) were included. After 1 month, there were significant differences among groups in plaque levels (P = 0.016) as test-1 showed less sites with plaque than test-2 (31.15% [standard error-SE 2.21%] versus 49.39% [SE 4.60%), respectively). No significant differences were found for global patient perception of the product or in adverse effects. Test groups showed better results in levels and proportions (P = 0.022) of Capnocytophaga spp. Within the limitations of this pilot study, it can be concluded that the newly formulated 0.12% CHX and 0.05% CPC mouthrinse showed larger plaque level reductions, without showing more adverse effects, when compared to the other two mouthrinses, after SRP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of DDT on bobwhite quail adrenal gland

USGS Publications Warehouse

Lehman, J.W.; Peterle, T.J.; Mulls, C.M.

1974-01-01

A wide range of responses to sublethal levels of DDT exist, many of which are species specific and vary within each species depending upon age, sex, and physiological state. Sublethal levels of DDT do cause an increase in the adrenal cortical tissue of bobwhite quail, which may cause increased secretion of corticosteroids, and in turn affect reproduction. A delicate homeostatic balance exists within the avian endocrine system which may be disturbed by feeding sublethal levels of chlorinated hydrocarbon pesticides. This adverse effect on the endocrine system may cause subtle reproductive failures which go unnoticed until the population is greatly reduced.

The Personality and Psychological Stress Predict Major Adverse Cardiovascular Events in Patients With Coronary Heart Disease After Percutaneous Coronary Intervention for Five Years

PubMed Central

Du, Jinling; Zhang, Danyang; Yin, Yue; Zhang, Xiaofei; Li, Jifu; Liu, Dexiang; Pan, Fang; Chen, Wenqiang

2016-01-01

Abstract To investigate the effects of personality type and psychological stress on the occurrence of major adverse cardiovascular events (MACEs) at 5 years in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Two hundred twenty patients with stable angina (SA) or non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with PCI completed type A behavioral questionnaire, type D personality questionnaire, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Trait Coping Style Questionnaire (TCSQ), and Symptom Checklist 90 (SCL-90) at 3 days after PCI operation. Meanwhile, biomedical markers (cTnI, CK-MB, LDH, LDH1) were assayed. MACEs were monitored over a 5-year follow-up. NSTE-ACS group had higher ratio of type A behavior, type A/D behavior, and higher single factor scores of type A personality and type D personality than control group and SAP group. NSTE-ACS patients had more anxiety, depression, lower level of mental health (P < 0.05; P < 0.01), more negative coping styles and less positive coping styles. The plasma levels of biomedical predictors had positive relation with anxiety, depression, and lower level of mental health. Type D patients were at a cumulative increased risk of adverse outcome compared with non-type D patients (P < 0.05). Patients treated with PCI were more likely to have type A and type D personality and this tendency was associated with myocardial injury. They also had obvious anxiety, depression emotion, and lower level of mental health, which were related to personality and coping style. Type D personality was an independent predictor of adverse events. PMID:27082597

[The problems of assessment of the high noise impact on the experts of the Air Force].

PubMed

Zinkin, V N; Sheshegov, P M

2012-01-01

Air Force specialists are exposed to high intensity noise levels exceeded the maximum permissible levels. Infrasound as a productive factor in accordance with the general technical requirements (OTT) Air Force-86 is not included in the list of standardized factors. The adverse acoustic environment makes the risk of occupational (sensorineural deafness) and professionally-related diseases of the nervous and cardiovascular systems. The system of physical fitness for military service in the Air Force and serving in the Air Force with high-intensity sources of noise, the system of treatment and preventive measures for adverse effects of noise and the procedure for examination of persons with diseases caused by the influence of noise are needed to be reviewed in accordance with the existing state legislative frameworks.

Safety of phase I clinical trials with monoclonal antibodies in Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster.

PubMed

Liedert, B; Bassus, S; Schneider, C K; Kalinke, U; Löwer, J

2007-01-01

This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only. The adverse effects associated with the TGN1412 Phase I trial indicate that the predictive value of pre-clinical animal models requires reevaluation and that, in certain cases, some issues of clinical trial protocols such as dose fixing may need refinement or redesign. Concrete safety measures, which have been proposed as a consequence of the TGN1412 event include introduction of criteria for high-risk antibodies, sequential inclusion of trial participants and implementation of pre-Phase I studies where dose calculation is based on the pre-clinical No Effect Level instead of the No Observed Adverse Effect Level. The recently established European clinical trials database (EUDRACT Database) is a further safety tool to expedite the sharing of relevant information between scientific authorities.

Estimating human-equivalent no observed adverse-effect levels for VOCs (volatile organic compounds) based on minimal knowledge of physiological parameters. Technical paper

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

Overton, J.H.; Jarabek, A.M.

1989-01-01

The U.S. EPA advocates the assessment of health-effects data and calculation of inhaled reference doses as benchmark values for gauging systemic toxicity to inhaled gases. The assessment often requires an inter- or intra-species dose extrapolation from no observed adverse effect level (NOAEL) exposure concentrations in animals to human equivalent NOAEL exposure concentrations. To achieve this, a dosimetric extrapolation procedure was developed based on the form or type of equations that describe the uptake and disposition of inhaled volatile organic compounds (VOCs) in physiologically-based pharmacokinetic (PB-PK) models. The procedure assumes allometric scaling of most physiological parameters and that the value ofmore » the time-integrated human arterial-blood concentration must be limited to no more than to that of experimental animals. The scaling assumption replaces the need for most parameter values and allows the derivation of a simple formula for dose extrapolation of VOCs that gives equivalent or more-conservative exposure concentrations values than those that would be obtained using a PB-PK model in which scaling was assumed.« less

Estimation of southern resident killer whale exposure to exhaust emissions from whale-watching vessels and potential adverse health effects and toxicity thresholds.

PubMed

Lachmuth, Cara L; Barrett-Lennard, Lance G; Steyn, D Q; Milsom, William K

2011-04-01

Southern resident killer whales in British Columbia and Washington are exposed to heavy vessel traffic. This study investigates their exposure to exhaust gases from whale-watching vessels by using a simple dispersion model incorporating data on whale and vessel behavior, atmospheric conditions, and output of airborne pollutants from the whale-watching fleet based on emissions data from regulatory agencies. Our findings suggest that current whale-watching guidelines are usually effective in limiting pollutant exposure to levels at or just below those at which measurable adverse health effects would be expected in killer whales. However, safe pollutant levels are exceeded under worst-case conditions and certain average-case conditions. To reduce killer whale exposure to exhaust we recommend: vessels position on the downwind side of whales, a maximum of 20 whale-watching vessels should be within 800 m at any given time, viewing periods should be limited, and current whale-watch guidelines and laws should be enforced. Copyright © 2011. Published by Elsevier Ltd.

Two cases of cutaneous leishmaniasis in Dutch military personnel treated with oral miltefosine.

PubMed

van der Snoek, Eric Martin; Couwenberg, S M; Stijnis, C; Kortbeek, L M; Schadd, E M

2017-02-01

In the Netherlands, cutaneous leishmaniasis is most commonly seen in military personnel deployed on a mission or training abroad. The treatment of two Dutch soldiers who acquired cutaneous leishmaniasis with oral miltefosine was evaluated. Adverse effects were monitored and the improvement of skin lesions was assessed. A military nurse with a painless Chiclero's ulcer due to Leishmania (Viannia) braziliensis acquired in Belize and a military physical training instructor with itchy swelling and small ulcer of the back of his left elbow due to L. donovani/infantum complex acquired in Ibiza were treated with oral miltefosine 50 mg three times a day for 28 days. Both patients responded well to oral miltefosine. Adverse effects were mild. Increase of creatinine levels was seen while liver transaminase levels were unremarkable. Miltefosine proved to be a convenient, effective and well-tolerated treatment option in the treatment of cutaneous leishmaniasis in Dutch military personnel. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Nonsteroidal Anti-inflammatory Drugs for Sciatica: An Updated Cochrane Review.

PubMed

Rasmussen-Barr, Eva; Held, Ulrike; Grooten, Wilhelmus J A; Roelofs, Pepijn D D M; Koes, Bart W; van Tulder, Maurits W; Wertli, Maria M

2017-04-15

Systematic review and meta-analysis. To determine the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on pain reduction, overall improvement, and reported adverse effects in people with sciatica. NSAIDs are one of the most frequently prescribed drugs for sciatica. We updated a 2008 Cochrane Review through June 2015. Randomized controlled trials that compared NSAIDs with placebo, with other NSAIDs, or with other medication were included. Outcomes included pain using mean difference (MD, 95% confidence intervals [95% CI]). For global improvement and adverse effects risk ratios (RR, 95% CI) were used. We assessed level of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Ten trials were included (N = 1651). Nine out of 10 trials were assessed at high risk of bias. For pain reduction (visual analog scale, 0 to 100) NSAIDs were no more effective than placebo (MD -4.56, 95% CI -11.11 to 1.99, quality of evidence: very low). For global improvement NSAIDs were more effective than placebo (RR 1.14 [95% CI 1.03 to 1.27], low quality of evidence). One trial reported the effect of NSAIDs on disability with very low-quality evidence that NSAIDs are no more effective than placebo. There was low-quality evidence that the risk for adverse effects is higher for NSAID than placebo (RR 1.40, 95% CI 1.02 to 1.93). Our findings show very low-quality evidence that the efficacy of NSAIDs for pain reduction is comparable with that of placebo, low-quality evidence that NSAIDs is better than placebo for global improvement and low-quality evidence for higher risk of adverse effects using NSAIDs compared with placebo. The findings must be interpreted with caution, due to small study samples, inconsistent results, and a high risk of bias in the included trials. 1.

Transformation of Air Quality Monitor Data from the International Space Station into Toxicological Effect Groups

NASA Technical Reports Server (NTRS)

James, John T.; Zalesak, Selina M.

2011-01-01

The primary reason for monitoring air quality aboard the International Space Station (ISS) is to determine whether air pollutants have collectively reached a concentration where the crew could experience adverse health effects. These effects could be near-real-time (e.g. headache, respiratory irritation) or occur late in the mission or even years later (e.g. cancer, liver toxicity). Secondary purposes for monitoring include discovery that a potentially harmful compound has leaked into the atmosphere or that air revitalization system performance has diminished. Typical ISS atmospheric trace pollutants consist of alcohols, aldehydes, aromatic compounds, halo-carbons, siloxanes, and silanols. Rarely, sulfur-containing compounds and alkanes are found at trace levels. Spacecraft Maximum Allowable Concentrations (SMACs) have been set in cooperation with a subcommittee of the National Research Council Committee on Toxicology. For each compound and time of exposure, the limiting adverse effect(s) has been identified. By factoring the analytical data from the Air Quality Monitor (AQM), which is in use as a prototype instrument aboard the ISS, through the array of compounds and SMACs, the risk of 16 specific adverse effects can be estimated. Within each adverse-effect group, we have used an additive model proportioned to each applicable 180-day SMAC to estimate risk. In the recent past this conversion has been performed using archival data, which can be delayed for months after an air sample is taken because it must be returned to earth for analysis. But with the AQM gathering in situ data each week, NASA is in a position to follow toxic-effect groups and correlate these with any reported crew symptoms. The AQM data are supplemented with data from real-time CO2 instruments aboard the ISS and from archival measurements of formaldehyde, which the AQM cannot detect.

Prenatal organochlorine and methylmercury exposure and memory and learning in school-age children in communities near the New Bedford Harbor Superfund site, Massachusetts.

PubMed

Orenstein, Sara T C; Thurston, Sally W; Bellinger, David C; Schwartz, Joel D; Amarasiriwardena, Chitra J; Altshul, Larisa M; Korrick, Susan A

2014-11-01

Polychlorinated biphenyls (PCBs), organochlorine pesticides, and methylmercury (MeHg) are environmentally persistent with adverse effects on neurodevelopment. However, especially among populations with commonly experienced low levels of exposure, research on neurodevelopmental effects of these toxicants has produced conflicting results. We assessed the association of low-level prenatal exposure to these contaminants with memory and learning. We studied 393 children, born between 1993 and 1998 to mothers residing near a PCB-contaminated harbor in New Bedford, Massachusetts. Cord serum PCB, DDE (dichlorodiphenyldichloroethylene), and maternal peripartum hair mercury (Hg) levels were measured to estimate prenatal exposure. Memory and learning were assessed at 8 years of age (range, 7-11 years) using the Wide Range Assessment of Memory and Learning (WRAML), age-standardized to a mean ± SD of 100 ± 15. Associations with each WRAML index-Visual Memory, Verbal Memory, and Learning-were examined with multivariable linear regression, controlling for potential confounders. Although cord serum PCB levels were low (sum of four PCBs: mean, 0.3 ng/g serum; range, 0.01-4.4), hair Hg levels were typical of the U.S. fish-eating population (mean, 0.6 μg/g; range, 0.3-5.1). In multivariable models, each microgram per gram increase in hair Hg was associated with, on average, decrements of -2.8 on Visual Memory (95% CI: -5.0, -0.6, p = 0.01), -2.2 on Learning (95% CI: -4.6, 0.2, p = 0.08), and -1.7 on Verbal Memory (95% CI: -3.9, 0.6, p = 0.14). There were no significant adverse associations of PCBs or DDE with WRAML indices. These results support an adverse relationship between low-level prenatal MeHg exposure and childhood memory and learning, particularly visual memory.

Experimental Study of a Three-Dimensional Shear-Driven Turbulent Boundary Layer with Streamwise Adverse Pressure Gradient

NASA Technical Reports Server (NTRS)

Driver, David M.; Johnston, James P.

1990-01-01

The effects of a strong adverse pressure gradient on a three-dimensional turbulent boundary layer are studied in an axisymmetric spinning cylinder geometry. Velocity measurements made with a three-component laser Doppler velocimeter include all three mean flow components, all six Reynolds stress components, and all ten triple-product correlations. Reynolds stress diminishes as the flow becomes three-dimensional. Lower levels of shear stress were seen to persist under adverse pressure gradient conditions. This low level of stress was seen to roughly correlate with the magnitude of cross-flow (relative to free stream flow) for this experiment as well as most of the other experiments in the literature. Variations in pressure gradient do not appear to alter this correlation. For this reason, it is hypothesized that a three-dimensional boundary layer is more prone to separate than a two-dimensional boundary layer, although it could not be directly shown here. None of the computations performed with either a Prandtl mixing length, k-epsilon, or a Launder-Reece-Rodi full Reynolds-stress model were able to predict the reduction in Reynolds stress.

IS THERE A VIABILITY-VULNERABILITY TRADEOFF? SEX DIFFERENCES IN FETAL PROGRAMMING

PubMed Central

SANDMAN, CURT A; GLYNN, LAURA M; DAVIS, ELYSIA POGGI

2013-01-01

OBJECTIVE In this paper we evaluate the evidence for sex differences in fetal programming within the context of the proposed viability-vulnerability tradeoff. METHODS We briefly review the literature on the factors contributing to primary and secondary sex ratios. Sex differences in fetal programming are assessed by summarizing previously published sex difference findings from our group (6 studies) and also new analyses of previously published findings in which sex differences were not reported (6 studies). RESULTS The review and reanalysis of studies from our group are consistent with the overwhelming evidence of increasing risk for viability among males exposed to environmental adversity early in life. New evidence reported here support the argument that females, despite their adaptive agility, also are influenced by exposure to early adversity. Two primary conclusions are (i) female fetal exposure to psychobiological stress selectively influences fear/anxiety, and (ii) the effects of female fetal exposure to stress persist into preadolescence. These persisting effects are reflected in increased levels of anxiety, impaired executive function and neurological markers associated with these behaviors. CONCLUSIONS A tacit assumption is that females, with their adaptive flexibility early in gestation, escape the consequences of early life exposure to adversity. We argue that the consequences of male exposure to early adversity threatens their viability, effectively culling the weak and the frail and creating a surviving cohort of the fittest. Females adjust to early adversity with a variety of strategies, but their escape from the risk of early mortality and morbidity has a price of increased vulnerability expressed later in development. PMID:24119938

Early-Life Effects on Adult Physical Activity: Concepts, Relevance, and Experimental Approaches.

PubMed

Garland, Theodore; Cadney, Marcell D; Waterland, Robert A

Locomotion is a defining characteristic of animal life and plays a crucial role in most behaviors. Locomotion involves physical activity, which can have far-reaching effects on physiology and neurobiology, both acutely and chronically. In human populations and in laboratory rodents, higher levels of physical activity are generally associated with positive health outcomes, although excessive exercise can have adverse consequences. Whether and how such relationships occur in wild animals is unknown. Behavioral variation among individuals arises from genetic and environmental factors and their interactions as well as from developmental programming (persistent effects of early-life environment). Although tremendous progress has been made in identifying genetic and environmental influences on individual differences in behavior, early-life effects are not well understood. Early-life effects can in some cases persist across multiple generations following a single exposure and, in principle, may constrain or facilitate the rate of evolution at multiple levels of biological organization. Understanding the mechanisms of such transgenerational effects (e.g., exposure to stress hormones in utero, inherited epigenetic alterations) may prove crucial to explaining unexpected and/or sex-specific responses to selection as well as limits to adaptation. One area receiving increased attention is early-life effects on adult physical activity. Correlational data from epidemiological studies suggest that early-life nutritional stress can (adversely) affect adult human activity levels and associated physiological traits (e.g., body composition, metabolic health). The few existing studies of laboratory rodents demonstrate that both maternal and early-life exercise can affect adult levels of physical activity and related phenotypes. Going forward, rodents offer many opportunities for experimental studies of (multigenerational) early-life effects, including studies that use maternal exposures and cross-fostering designs.

Mindfulness as a mediator of the association between adverse childhood experiences and alcohol use and consequences.

PubMed

Brett, Emma I; Espeleta, Hannah C; Lopez, Susanna V; Leavens, Eleanor L S; Leffingwell, Thad R

2018-09-01

One-third of college students report past-year heavy episodic drinking, making college student alcohol use an important area for continued research. Research has consistently linked early experiences of adversity to problematic substance use in adolescence and adulthood. Given the negative health consequences associated with heavy episodic drinking, it is imperative to identify mechanisms that contribute to this relation. Low levels of mindfulness have been linked to early adversity as well as impulsivity and alcohol use, therefore, the current study aims to examine the mediating role of mindfulness in the relation between early adversity and current alcohol use and consequences. Undergraduate students (N = 385) at a Midwestern university completed an online questionnaire assessing experiences of childhood adversity, trait mindfulness, and current alcohol use and related consequences. Results indicated that increased adverse experiences and lower levels of mindfulness predicted both increased alcohol consumption and consequences (ps < 0.025), with mindfulness mediating the relationships. Mindfulness is a predictor of alcohol outcomes and appears to mediate the relation between early adversity and alcohol use and consequences. Findings suggest that students with a history of adversity are more likely to exhibit lower levels of mindfulness, which may lead to an increase in alcohol consumption and consequences in early adulthood. Targeted alcohol intervention efforts that incorporate mindfulness skills may be particularly beneficial for those who have experienced early adversity. Copyright © 2018. Published by Elsevier Ltd.

Testing quantitative adverse outcome pathway predictions using aromatase inhibitors in female fathead minnows

EPA Science Inventory

To become more efficient and cost effective regulatory toxicology is increasingly averting from whole animal testing toward collecting data at lower levels of biological organization, through such means as in vitro high throughput screening (HTS) assays. When anchored to relevant...

Practical examples of modeling choices and their consequences for risk assessment

EPA Science Inventory

Although benchmark dose (BMD) modeling has become the preferred approach to identifying a point of departure (POD) over the No Observed Adverse Effect Level, there remain challenges to its application in human health risk assessment. BMD modeling, as currently implemented by the...

Current State of the Evidence: Air Pollution Impacts on Human Health

EPA Science Inventory

Epidemiologic studies have demonstrated a consistent association between ambient levels of air pollution and adverse human health effects, including mortality and morbidity. Many of these studies have relied on the US Air Quality System (AQS) for exposure assessment. The AQS is a...

15 CFR 923.25 - Shoreline erosion/mitigation planning.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL... effects of, and studying and evaluating ways to control, or lessen the impact of, shoreline erosion, including potential impacts of sea level rise, and to restore areas adversely affected by such erosion. This...

15 CFR 923.25 - Shoreline erosion/mitigation planning.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL... effects of, and studying and evaluating ways to control, or lessen the impact of, shoreline erosion, including potential impacts of sea level rise, and to restore areas adversely affected by such erosion. This...

15 CFR 923.25 - Shoreline erosion/mitigation planning.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL... effects of, and studying and evaluating ways to control, or lessen the impact of, shoreline erosion, including potential impacts of sea level rise, and to restore areas adversely affected by such erosion. This...

DEVELOPMENT OF EXPOSURE-RESPONSE RELATIONSHIPS BETWEEN INDICATORS OF WATER QUALITY AND SWIMMING-ASSOCIATED ILLNESS

EPA Science Inventory

Exposure to contaminated water during recreational swimming has long been associated with adverse health effects. Swimming in rivers, streams and lakes with high levels of fecal contamination are regularly linked to outbreaks of gastrointestinal illness and related infections. Wh...

IDENTIFICATION OF CHLORINE DIOXIDE DRINKING WATER DISINFECTION BY-PRODUCTS FORMED AT HIGH BROMIDE LEVELS

EPA Science Inventory

Due to concern over the potential adverse health effects of trihalomethanes (THMs), haloacetic acids, and other chlorinated by-products in chlorinated drinking water, alternative disinfection methods are being explored. Chlorine dioxide is a popular alternative, with over 500 dri...

Silage review: Mycotoxins in silage: Occurrence, effects, prevention, and mitigation.

PubMed

Ogunade, I M; Martinez-Tuppia, C; Queiroz, O C M; Jiang, Y; Drouin, P; Wu, F; Vyas, D; Adesogan, A T

2018-05-01

Ensiled forage, particularly corn silage, is an important component of dairy cow diets worldwide. Forages can be contaminated with several mycotoxins in the field pre-harvest, during storage, or after ensiling during feed-out. Exposure to dietary mycotoxins adversely affects the performance and health of livestock and can compromise human health. Several studies and surveys indicate that ruminants are often exposed to mycotoxins such as aflatoxins, trichothecenes, ochratoxin A, fumonisins, zearalenone, and many other fungal secondary metabolites, via the silage they ingest. Problems associated with mycotoxins in silage can be minimized by preventing fungal growth before and after ensiling. Proper silage management is essential to reduce mycotoxin contamination of dairy cow feeds, and certain mold-inhibiting chemical additives or microbial inoculants can also reduce the contamination levels. Several sequestering agents also can be added to diets to reduce mycotoxin levels, but their efficacy varies with the type and level of mycotoxin contamination. This article gives an overview of the types, prevalence, and levels of mycotoxin contamination in ensiled forages in different countries, and describes their adverse effects on health of ruminants, and effective prevention and mitigation strategies for dairy cow diets. Future research priorities discussed include research efforts to develop silage additives or rumen microbial innocula that degrade mycotoxins. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Noise-induced hearing loss in children and youth: causes and prevention].

PubMed

Sułkowski, Wiesław J

2009-01-01

The populations at risk of adverse effects of noise include, in addition to adults, also children and juveniles, the two groups considered to be particularly vulnerable to noise-induced hearing loss and numerous other adverse systemic effects of exposure to noise. Major sources of noise exposure in children's and youth's environments include incubators at neonate intensive care wards, toys (such as e.g. rattles, squeeze toys, percussion cap toys, pistols), fireworks, pop and rock music concerts, aerobic courses and personal portable music players. This paper reports dB-A noise levels associated with those noise sources, and also combined dB-A levels of noise from external and internal sources prevailing at schools. The suggested preventive steps specified in the CE-HAPE (Children's Environment and Health Action Plan for Europe) and PINCHE (Policy Interpretation Network on Children's Health and Environment) include legislative measures to limit the intensity and time of exposure to noise and classes/education actions for youths and parents.

Risk assessment derived from migrants identified in several adhesives commonly used in food contact materials.

PubMed

Canellas, E; Vera, P; Nerín, C

2015-01-01

Adhesives are used to manufacture multilayer materials, where their components pass through the layers and migrate to the food. Nine different adhesives (acrylic, vinyl and hotmelt) and their migration in 21 laminates for future use as market samples have been evaluated and risk assessment has been carried out. A total of 75 volatiles and non volatile compounds were identified by gas chromatography-mass spectrometry and ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Most of the compounds migrated below their specific migration limit (SML), lowest observed adverse effect level (LOAEL), no observed adverse effect level (NOAEL) and values recommended by Cramer. Six compounds classified as high toxicity class III according to Cramer classification, migrated over their SML and exposure values recommended by Cramer, when they were applied in the full area of the packaging. Nevertheless, these adhesives fulfill the threshold in the real application as they are applied in a small area of the packaging. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-invasive subcutaneous fat reduction: a review.

PubMed

Kennedy, J; Verne, S; Griffith, R; Falto-Aizpurua, L; Nouri, K

2015-09-01

The risks, financial costs and lengthy downtime associated with surgical procedures for fat reduction have led to the development of a number of non-invasive techniques. Non-invasive body contouring now represents the fastest growing area of aesthetic medicine. There are currently four leading non-invasive techniques for reducing localized subcutaneous adipose tissue: low-level laser therapy (LLLT), cryolipolysis, radio frequency (RF) and high-intensity focused ultrasound (HIFU). To review and compare leading techniques and clinical outcomes of non-invasive subcutaneous fat reduction. The terms 'non-invasive', 'low-level laser', 'cryolipolysis', 'ultrasound' and 'radio frequency' were combined with 'lipolysis', 'fat reduction' or 'body contour' during separate searches in the PubMed database. We identified 31 studies (27 prospective clinical studies and four retrospective chart reviews) with a total of 2937 patients that had been treated with LLLT (n = 1114), cryolipolysis (n = 706), HIFU (n = 843) or RF (n = 116) or other techniques (n = 158) for fat reduction or body contouring. A majority of these patients experienced significant and satisfying results without any serious adverse effects. The studies investigating these devices have all varied in treatment regimen, body locations, follow-up times or outcome operationalization. Each technique differs in offered advantages and severity of adverse effects. However, multiple non-invasive devices are safe and effective for circumferential reduction in local fat tissue by 2 cm or more across the abdomen, hips and thighs. Results are consistent and reproducible for each device and none are associated with any serious or permanent adverse effects. © 2015 European Academy of Dermatology and Venereology.

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. (1...

Chronic effects of air pollution on respiratory health in Southern California children: findings from the Southern California Children’s Health Study

PubMed Central

Chen, Zhanghua; Salam, Muhammad T.; Eckel, Sandrah P.; Breton, Carrie V.

2015-01-01

Outdoor air pollution is one of the leading contributors to adverse respiratory health outcomes in urban areas around the world. Children are highly sensitive to the adverse effects of air pollution due to their rapidly growing lungs, incomplete immune and metabolic functions, patterns of ventilation and high levels of outdoor activity. The Children’s Health Study (CHS) is a continuing series of longitudinal studies that first began in 1993 and has focused on demonstrating the chronic impacts of air pollution on respiratory illnesses from early childhood through adolescence. A large body of evidence from the CHS has documented that exposures to both regional ambient air and traffic-related pollutants are associated with increased asthma prevalence, new-onset asthma, risk of bronchitis and wheezing, deficits of lung function growth, and airway inflammation. These associations may be modulated by key genes involved in oxidative-nitrosative stress pathways via gene-environment interactions. Despite successful efforts to reduce pollution over the past 40 years, air pollution at the current levels still brings many challenges to public health. To further ameliorate adverse health effects attributable to air pollution, many more toxic pollutants may require regulation and control of motor vehicle emissions and other combustion sources may need to be strengthened. Individual interventions based on personal susceptibility may be needed to protect children’s health while control measures are being implemented. PMID:25694817

Noise monitoring and adverse health effects in residents in different functional areas of Luzhou, China.

PubMed

Han, Zhi-Xia; Lei, Zhang-Heng; Zhang, Chun-Lian; Xiong, Wei; Gan, Zhong-Lin; Hu, Ping; Zhang, Qing-Bi

2015-03-01

The purpose of the study was to investigate the noise pollution situation and the resulting adverse effect on residents' health in Luzhou, China, to provide data for noise pollution prevention policies and interventions. Four different functional areas (commercial, construction, residential, and transportation hub areas) were chosen to monitor noise level for 3 months. The survey was performed by questionnaire on the spot on randomly selected individuals; it collected data on the impact of noise on residents' health (quality of sleep, high blood pressure, subjective feeling of nervous system damage, and attention) as well as the knowledge of noise-induced health damage, the degree of adaptation to noise, and their solutions. The noise levels of residential, commercial, transportation, and construction areas exceeded the national standards (P < .001). Sleep quality, prevalence of hypertension, and attention in transportation hub areas were significantly different from those in the other 3 areas (P < .05); only 24.46% of people knew the health hazards associated with noise; 64.57% of residents have adapted to the current noise environment. Most of them have to close the doors and windows to reduce noise. The noise pollution situation in Luzhou, China, is serious, especially the traffic noise pollution. Residents pay less attention to it and adopt single measures to reduce the noise. We should work toward the prevention and control of traffic noise and improve the residents' awareness to reduce the adverse health effects of noise. © 2014 APJPH.

Silver oxysalts promote cutaneous wound healing independent of infection.

PubMed

Thomason, Helen A; Lovett, Jodie M; Spina, Carla J; Stephenson, Christian; McBain, Andrew J; Hardman, Matthew J

2018-03-12

Chronic wounds often exist in a heightened state of inflammation whereby excessive inflammatory cells release high levels of proteases and reactive oxygen species (ROS). While low levels of ROS play a fundamental role in the regulation of normal wound healing, their levels need to be tightly regulated to prevent a hostile wound environment resulting from excessive levels of ROS. Infection amplifies the inflammatory response, augmenting levels of ROS which creates additional tissue damage that supports microbial growth. Antimicrobial dressings are used to combat infection; however, the effects of these dressing on the wound environment and healing independent of infection are rarely assessed. Cytotoxic or adverse effects on healing may exacerbate the hostile wound environment and prolong healing. Here we assessed the effect on healing independent of infection of silver oxysalts which produce higher oxidative states of silver (Ag 2+ /Ag 3+ ). Silver oxysalts had no adverse effect on fibroblast scratch wound closure whilst significantly promoting closure of keratinocyte scratch wounds (34% increase compared with control). Furthermore, dressings containing silver oxysalts accelerated healing of full-thickness incisional wounds in wild-type mice, reducing wound area, promoting reepithelialization, and dampening inflammation. We explored the mechanisms by which silver oxysalts promote healing and found that unlike other silver dressings tested, silver oxysalt dressings catalyze the breakdown of hydrogen peroxide to water and oxygen. In addition, we found that silver oxysalts directly released oxygen when exposed to water. Collectively, these data provide the first indication that silver oxysalts promote healing independent of infection and may regulate oxidative stress within a wound through catalysis of hydrogen peroxide. © 2018 by the Wound Healing Society.

The lack of knowledge about the voluntary reporting system of adverse drug reactions as a major cause of underreporting: direct survey among health professionals.

PubMed

Pérez García, Mariley; Figueras, Albert

2011-12-01

Underreporting suspected adverse drug reactions (ADRs) is one of the main problems that face the pharmacovigilance (PhV) systems based on yellow card schemes. To measure the knowledge level on the suspected ADR voluntary reporting system among physicians and pharmacists in Venezuela and to study its relationship with different variables. A population-based, anonymous, and self-administered questionnaire was addressed to health professionals along the national territory of Venezuela. An algorithm was developed to classify the knowledge level on the voluntary reporting system. Taken as a whole, the level of knowledge on the voluntary reporting system was "poor." Among the 515 participant physicians, 62.3% (95%CI = 58.0-66.5%) had a "poor" level of knowledge; PhV was associated with "control" of medicines use, and only 24.7% had ever reported a suspected ADR. "Medical specialty" was the only variable that showed a relationship with the knowledge level (p = 0.0041). Among the 78 participant pharmacists, 66.7% had a "poor" knowledge level (95%CI = 55.1-76.9%). The knowledge level on the voluntary reporting system among physicians and pharmacists in Venezuela is poor. These results strengthen the hypothesis that being unaware of the adverse effects of medicines and not knowing the existence of a PhV system is a major cause of underreporting. A careful study of the actual knowledge of PhV could be the basis to set up interventions specifically designed to overcome misleading concepts and to improve the reporting rate at a national level. Copyright © 2011 John Wiley & Sons, Ltd.

Contrast Media Use in Radiation Oncology: A Prospective, Controlled Educational Intervention Study with Retrospective Analysis of Patient Outcomes

PubMed Central

Barker, Christopher A.; Mutter, Robert W.; Shapiro, Lauren Q.; Zhang, Zhigang; Wolden, Suzanne L.; Yahalom, Joachim

2016-01-01

Purpose Intravenous contrast media (ICM) administration is recommended as part of radiation therapy (RT) simulation in a variety of clinical scenarios, but can cause adverse events. We sought to assess radiation oncology resident knowledge about ICM, and to determine if an educational intervention (EI) could improve this level of knowledge. In conjunction, we retrospectively analyzed risk factors and adverse events related to ICM use before and after the EI to determine whether any improvements in patient outcomes could be realized. Methods Over 2 years, 21 residents in radiation oncology at Memorial Sloan-Kettering Cancer Center (MSKCC) participated in a pretest-EI-posttest study based on the ACR’s Manual on Contrast Media. Medical and RT records were reviewed, and ICM use, risk factors and adverse events were recorded. Results There was no significant difference in resident understanding of ICM use in residents of different years of training (p=0.85). Understanding of ICM use increased in residents that attended the EI (p<0.05), but this was not sustained 1 year after the EI (p=0.48). Of the 6852 RT simulations that were performed at MSKCC, 1350 (19.7%) involved ICM. Mild adverse events occurred in a few patients (<5%) simulated with ICM, but there was no difference in the number of risk factors or adverse events before and after the EI. Conclusions The EI effectively improved short-term understanding of ICM use. However, the effect was not sustained. The frequency of adverse events related to ICM use was small and not significantly impacted by the EI. PMID:21129689

Adverse adolescent relationship histories and young adult health: Cumulative effects of loneliness, low parental support, relationship instability, intimate partner violence and loss

PubMed Central

Adam, Emma K.; Chyu, Laura; Hoyt, Lindsay; Doane, Leah D.; Boisjoly, Johanne; Duncan, Greg; Chase-Lansdale, Lindsay; McDade, Thomas W.

2011-01-01

Purpose To examine the associations between adverse interpersonal relationship histories experienced during adolescence and health in young adulthood in a large, nationally representative sample. Methods Using data from Waves I, II and III of the National Longitudinal Study of Adolescent Health, multiple adverse relationship experiences are examined, including high loneliness, low perceived parental support, frequent transitions in romantic relationships (relationship instability), exposure to intimate partner violence, and loss by death of important relationship figures. These histories are assessed, both individually and in a relationship risk index, as predictors of self-reported general health and depressive symptoms at Wave III (ages 18 to 27), controlling for baseline (Wave I) health and for demographic and health behavior covariates. Results Net of baseline health and covariates, each type of relationship risk (experienced between Wave I and Wave III) was related to either depression or general health at Wave III, with the strongest effects seen for exposure to intimate partner violence. In addition, a cumulative relationship risk index examining the extent to which youth experienced high levels of multiple relationship risk factors revealed that each additional adverse relationship experience increased the odds of reporting poor mental and general health at Wave III, with increases occurring in an additive manner. Conclusions Multiple types of adverse relationship experiences predicted increases in poor general health and depressive symptoms from adolescence to early adulthood. Consistent with a cumulative risk hypothesis, the more types of adverse relationship experiences a youth experienced, the worse their young adult health outcomes. PMID:21856520

Mercury, Lead, Cadmium, Cobalt, Arsenic and Selenium in the Blood of Semipalmated Sandpipers (Calidris pusilla) from Suriname, South America: Age-related Differences in Wintering Site and Comparisons with a Stopover Site in New Jersey, USA.

PubMed

Burger, Joanna; Mizrahi, David; Tsipoura, Nellie; Jeitner, Christian; Gochfeld, Michael

2018-05-09

It is essential to understand contaminant exposure and to compare levels of contaminants in organisms at different ages to determine if there is bioaccumulation, and to compare levels encountered in different geographical areas. In this paper, we report levels of mercury, lead, cadmium, cobalt, arsenic and selenium in the blood of semipalmated sandpipers ( Calidris pusilla ) wintering in Suriname as a function of age, and compare them to blood levels in northbound migrants at a stopover in Delaware Bay, New Jersey. We found (1) young birds had higher levels of cadmium, cobalt, and lead than adults (after second year birds); (2) there were no age-related differences for arsenic, mercury and selenium; (3) only four of the possible 16 inter-metal correlations were significant, at the 0.05 level; (4) the highest correlation was between cadmium and lead (Kendall tau = 0.37); and (5) the adult sandpipers had significantly higher levels of cadmium, mercury and selenium in Suriname than in New Jersey, while the New Jersey birds had significantly higher levels of arsenic. Suriname samples were obtained in April, after both age classes had spent the winter in Suriname, which suggests that sandpipers are accumulating higher levels of trace elements in Suriname than in Delaware Bay. The levels of selenium may be within a range of concern for adverse effects, but little is known about adverse effect levels of trace elements in the blood of wild birds.

Significance of the DNA-Histone Complex Level as a Predictor of Major Adverse Cardiovascular Events in Hemodialysis Patients: The Effect of Uremic Toxin on DNA-Histone Complex Formation.

PubMed

Jeong, Jong Cheol; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Ryu, Ji Won; Kim, Dong Ki; Joo, Kwon Wook; Kim, Hyun Kyung

2016-01-01

Neutrophils can release the DNA-histone complex into circulation following exposure to inflammatory stimuli. This prospective study investigated whether the DNA-histone complex and other biomarkers could predict major cardiovascular adverse events (MACEs) in hemodialysis (HD) patients. The levels of circulating DNA-histone complexes, cell-free DNA, interleukin (IL)-6, and neutrophil elastase were measured in 60 HD patients and 28 healthy controls. MACE was assessed at 24 months. Uremic toxin-induced neutrophil released contents were measured in vitro. Compared with controls, HD patients showed higher levels of DNA-histone complexes and IL-6. The DNA-histone complex level was inversely associated with the Kt/V. In a multivariable Cox analysis, the high level of DNA-histone complexes was a significant independent predictor of MACE. The uremic toxins induced DNA-histone complex formation in normal neutrophils in vitro. The DNA-histone complex is a potentially useful marker to predict MACE in HD patients. Uremic toxins induced DNA-histone complex formation in vitro. © 2015 S. Karger AG, Basel.

Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes

PubMed Central

Kundakovic, Marija; Lim, Sean; Gudsnuk, Kathryn; Champagne, Frances A.

2013-01-01

Early life adversity can have a significant long-term impact with implications for the emergence of psychopathology. Disruption to mother-infant interactions is a form of early life adversity that may, in particular, have profound programing effects on the developing brain. However, despite converging evidence from human and animal studies, the precise mechanistic pathways underlying adversity-associated neurobehavioral changes have yet to be elucidated. One approach to the study of mechanism is exploration of epigenetic changes associated with early life experience. In the current study, we examined the effects of postnatal maternal separation (MS) in mice and assessed the behavioral, brain gene expression, and epigenetic effects of this manipulation in offspring. Importantly, we included two different mouse strains (C57BL/6J and Balb/cJ) and both male and female offspring to determine strain- and/or sex-associated differential response to MS. We found both strain-specific and sex-dependent effects of MS in early adolescent offspring on measures of open-field exploration, sucrose preference, and social behavior. Analyses of cortical and hippocampal mRNA levels of the glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf) genes revealed decreased hippocampal Bdnf expression in maternally separated C57BL/6J females and increased cortical Bdnf expression in maternally separated male and female Balb/cJ offspring. Analyses of Nr3c1and Bdnf (IV and IX) CpG methylation indicated increased hippocampal Nr3c1 methylation in maternally separated C57BL/6J males and increased hippocampal Bdnf IX methylation in male and female maternally separated Balb/c mice. Overall, though effect sizes were modest, these findings suggest a complex interaction between early life adversity, genetic background, and sex in the determination of neurobehavioral and epigenetic outcomes that may account for differential vulnerability to later-life disorder. PMID:23914177

Mefloquine adverse effects with atypical facial lesions in an overweight patient.

PubMed

Descloux, Elodie; De Monbrison, Frédérique; Basselin, Cécile; Vial, Thierry; Peyron, François

2010-09-01

The recommended dosage of mefloquine to treat Plasmodium falciparum infection is 25 mg/kg, with no recommendation for dosage exceeding 1500 mg. We describe an original case of adverse reaction to mefloquine in an overweight patient. Case report. A 32-year-old woman weighing 139 kg presented with uncomplicated P. falciparum infection after returning from Cameroon. She received 3250 mg of mefloquine (i.e. 23 mg/kg) administered in four doses. On day 2, she developed neuropsychiatric disorders and facial lesions. Nasal mucocutaneous vesicles and bullae, depressive mood, mild thrombocytopenia and hepatic cytolysis were evidenced. Parasitemia was negative. Recovery was complete on day 17. High mefloquine serum levels were measured (8.030 mg/L on day 3, 6.880 mg/L on day 8, and 3.370 mg/L on day 17). The causal relationship between mefloquine and the occurrence of these adverse effects is probable. However, as no viral or bacteriological investigations were performed, the drug responsibility remains uncertain. Mefloquine-induced bullous and facial lesions reversible upon drug withdrawal have already been described. The associated neuropsychiatric symptoms were strongly suggestive of mefloquine adverse effects, as such events are more frequently observed in cases of overdosage. Our case emphasizes the difficulties of dosage adaptation in overweight patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Milk--the promoter of chronic Western diseases.

PubMed

Melnik, Bodo C

2009-06-01

Common chronic diseases of Western societies, such as coronary heart disease, diabetes mellitus, cancer, hypertension, obesity, dementia, and allergic diseases are significantly influenced by dietary habits. Cow's milk and dairy products are nutritional staples in most Western societies. Milk and dairy product consumption is recommended by most nutritional societies because of their beneficial effects for calcium uptake and bone mineralization and as a source of valuable protein. However, the adverse long-term effects of milk and milk protein consumption on human health have been neglected. A hypothesis is presented, showing for the first time that milk protein consumption is an essential adverse environmental factor promoting most chronic diseases of Western societies. Milk protein consumption induces postprandial hyperinsulinaemia and shifts the growth hormone/insulin-like growth factor-1 (IGF-1) axis to permanently increased IGF-1 serum levels. Insulin/IGF-1 signalling is involved in the regulation of fetal growth, T-cell maturation in the thymus, linear growth, pathogenesis of acne, atherosclerosis, diabetes mellitus, obesity, cancer and neurodegenerative diseases, thus affecting most chronic diseases of Western societies. Of special concern is the possibility that milk intake during pregnancy adversely affects the early fetal programming of the IGF-1 axis which will influence health risks later in life. An accumulated body of evidence for the adverse effects of cow's milk consumption from fetal life to childhood, adolescence, adulthood and senescence will be provided which strengthens the presented hypothesis.

Derivation of occupational exposure levels (OELs) of low-toxicity isometric biopersistent particles: How can the kinetic lung overload paradigm be used for improved inhalation toxicity study design and OEL-derivation?

PubMed

Pauluhn, Jürgen

2014-12-20

Convincing evidence suggests that poorly soluble low-toxicity particles (PSP) exert two unifying major modes of action (MoA), in which one appears to be deposition-related acute, whilst the other is retention-related and occurs with particle accumulation in the lung and associated persistent inflammation. Either MoA has its study- and cumulative dose-specific adverse outcome and metric. Modeling procedures were applied to better understand as to which extent protocol variables may predetermine any specific outcome of study. The results from modeled and empirical studies served as basis to derive OELs from modeled and empirically confirmed directions. This analysis demonstrates that the accumulated retained particle displacement volume was the most prominent unifying denominator linking the pulmonary retained volumetric particle dose to inflammogenicity and toxicity. However, conventional study design may not always be appropriate to unequivocally discriminate the surface thermodynamics-related acute adversity from the cumulative retention volume-related chronic adversity. Thus, in the absence of kinetically designed studies, it may become increasingly challenging to differentiate substance-specific deposition-related acute effects from the more chronic retained cumulative dose-related effects. It is concluded that the degree of dissolution of particles in the pulmonary environment seems to be generally underestimated with the possibility to attribute to toxicity due to decreased particle size and associated changes in thermodynamics and kinetics of dissolution. Accordingly, acute deposition-related outcomes become an important secondary variable within the pulmonary microenvironment. In turn, lung-overload related chronic adversities seem to be better described by the particle volume metric. This analysis supports the concept that 'self-validating', hypothesis-based computational study design delivers the highest level of unifying information required for the risk characterization of PSP. In demonstrating that the PSP under consideration is truly following the generic PSP-paradigm, this higher level of mechanistic information reduces the potential uncertainty involved with OEL derivation.

N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish.

PubMed

Robinson, Bonnie; Dumas, Melanie; Gu, Qiang; Kanungo, Jyotshna

2018-06-08

N-acetylcysteine, a precursor molecule of glutathione, is an antioxidant. Ketamine, a pediatric anesthetic, has been implicated in cardiotoxicity and neurotoxicity including modulation of monoaminergic systems in mammals and zebrafish. Here, we show that N-acetylcysteine prevents ketamine's adverse effects on development and monoaminergic neurons in zebrafish embryos. The effects of ketamine and N-acetylcysteine alone or in combination were measured on the heart rate, body length, brain serotonergic neurons and tyrosine hydroxylase-immunoreactive (TH-IR) neurons. In the absence of N-acetylcysteine, a concentration of ketamine that produces an internal embryo exposure level comparable to human anesthetic plasma concentrations significantly reduced heart rate and body length and those effects were prevented by N-acetylcysteine co-treatment. Ketamine also reduced the areas occupied by serotonergic neurons in the brain, whereas N-acetylcysteine co-exposure counteracted this effect. TH-IR neurons in the embryo brain and TH-IR cells in the trunk were significantly reduced with ketamine treatment, but not in the presence of N-acetylcysteine. In our continued search for compounds that can prevent ketamine toxicity, this study using specific endpoints of developmental toxicity, cardiotoxicity and neurotoxicity, demonstrates protective effects of N-acetylcysteine against ketamine's adverse effects. This is the first study that shows the protective effects of N-acetylcysteine on ketamine-induced developmental defects of monoaminergic neurons as observed in a whole organism. Published by Elsevier B.V.

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. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

A rare adverse effect of metronidazole: nervous system symptoms.

PubMed

Kafadar, Ihsan; Moustafa, Fatma; Yalçın, Koray; Klç, Betül Aydn

2013-06-01

Metronidazole, as a 5-nitroimidazole compound, is effective on anaerobic bacteria and protozoon diseases. Mostly, metronidazole is a tolerable drug but rarely presents serious adverse effects on the nervous system. In case of these adverse effects, treatment must be stopped.In this report, a 3-year-old child hospitalized because of diarrhea is presented. During the metronidazole treatment, loss of sight, vertigo, ataxia, and headache occurred as the adverse effects. By this report, we want to express the rare adverse effects of drugs in the differential diagnoses of nervous system diseases.

Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak

PubMed Central

Lancee, William J.; Balderson, Kenneth E.; Bennett, Jocelyn P.; Borgundvaag, Bjug; Evans, Susan; Fernandes, Christopher M.B.; Goldbloom, David S.; Gupta, Mona; Hunter, Jonathan J.; Hall, Linda McGillis; Nagle, Lynn M.; Pain, Clare; Peczeniuk, Sonia S.; Raymond, Glenna; Read, Nancy; Rourke, Sean B.; Steinberg, Rosalie J.; Stewart, Thomas E.; Coke, Susan VanDeVelde; Veldhorst, Georgina G.; Wasylenki, Donald A.

2006-01-01

Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks. PMID:17326946

Lack of Response in an Autistic Population to a Low Dose Clinical Trial of Pyridoxine Plus Magnesium.

ERIC Educational Resources Information Center

Tolbert, Lelland; And Others

1993-01-01

As some therapeutic benefits for autistic persons have been reported from combined high doses of pyridoxine and magnesium, this study evaluated long-term administration of low doses (to minimize adverse effects) to 15 subjects with autism. Findings indicated that, at this dosage level, pyridoxine and magnesium had no effect on the severity of…

Effects of turbidity, sediment, and polyacrylamide on native freshwater mussels

USGS Publications Warehouse

Buczek, Sean B.; Cope, W. Gregory; McLaughlin, Richard A.; Kwak, Thomas J.

2018-01-01

Turbidity is a ubiquitous pollutant adversely affecting water quality and aquatic life in waterways globally. Anionic polyacrylamide (PAM) is widely used as an effective chemical flocculent to reduce suspended sediment (SS) and turbidity. However, no information exists on the toxicity of PAM‐flocculated sediments to imperiled, but ecologically important, freshwater mussels (Unionidae). Thus, we conducted acute (96 h) and chronic (24 day) laboratory tests with juvenile fatmucket (Lampsilis siliquoidea) and three exposure conditions (nonflocculated settled sediment, SS, and PAM‐flocculated settled sediment) over a range of turbidity levels (50, 250, 1,250, and 3,500 nephelometric turbidity units). Survival and sublethal endpoints of protein oxidation, adenosine triphosphate (ATP) production, and protein concentration were used as measures of toxicity. We found no effect of turbidity levels or exposure condition on mussel survival in acute or chronic tests. However, we found significant reductions in protein concentration, ATP production, and oxidized proteins in mussels acutely exposed to the SS condition, which required water movement to maintain sediment in suspension, indicating responses that are symptoms of physiological stress. Our results suggest anionic PAM applied to reduce SS may minimize adverse effects of short‐term turbidity exposure on juvenile freshwater mussels without eliciting additional lethal or sublethal toxicity.

Adherence to Medical Cannabis Among Licensed Patients in Israel.

PubMed

Zolotov, Yuval; Baruch, Yehuda; Reuveni, Haim; Magnezi, Racheli

2016-01-01

Objectives: To evaluate adherence among Israeli patients who are licensed to use medical cannabis and to identify factors associated with adherence to medical cannabis. Methods: Ninety-five novice licensed patients were interviewed for this cross-sectional study. The questionnaire measured demographics, the perceived patient-physician relationship, and the level of patients' active involvement in their healthcare. In addition, patients were queried about adverse effect(s) and about their overall satisfaction from this medical treatment. Results: Eighty percent ( n =76) has been identified as adherent to medical cannabis use. Variables found associated with adherence were "country of origin" (immigrant status), "type of illness" (cancer vs. non-cancer), and "experiencing adverse effect(s)." Three predictors of adherence were found significant in a logistic regression model: "type of illness" (odds ratio [OR] 0.101), patient-physician relationship (OR 1.406), and level of patient activation (OR 1.132). 71.5% rated themselves being "completely satisfied" or "satisfied" from medical cannabis use. Conclusions: Our findings show a relatively high adherence rate for medical cannabis, as well as relative safety and high satisfaction among licensed patients. Additionally indicated is the need to develop and implement standardized education about this evolving field-to both patients and physicians.

Add-on effects of a low-dose aripiprazole in resolving hyperprolactinemia induced by risperidone or paliperidone.

PubMed

Qiao, Ying; Yang, Fuzhong; Li, Chunbo; Guo, Qian; Wen, Hui; Zhu, Suoyu; Ouyang, Qiong; Shen, Weidi; Sheng, Jianhua

2016-03-30

This study investigated the effects of a low-dose aripiprazole adjunctive treatment for risperidone- or paliperidone-induced hyperprolactinemia in Han Chinese women with schizophrenia. After 4 weeks of risperidone or paliperidone treatment, 60 out of 66 patients improved significantly and experienced hyperprolactinemia. They were randomly assigned to the treatment group (aripiprazole adjunctive treatment) (n=30) or control group (non-adjunctive treatment) (n=30). The dosage of risperidone and paliperidone were maintained; and aripiprazole was maintained at 5mg/day during the 8-week study period. The prolactin levels at the end of the 8th week were significantly lower in the treatment group than in the control group. The estradiol level correlated negatively with serum prolactin level both in the treatment group and the control group at the end of the 8th week and the 4th week respectively. The Positive and Negative Syndrome Scale score improved significantly during the 8-week study period in both groups. The incidence of treatment-emergent adverse event was similar in two groups. Low-dose aripiprazole adjunctive treatment is effective in relieving risperidone- and paliperidone-induced hyperprolactinemia in female schizophrenic patients without increasing adverse event. Copyright © 2016. Published by Elsevier Ireland Ltd.

Patient perspectives on low level light therapy and laser therapies for rosacea-associated persistent facial redness.

PubMed

McGinley, Meagan; Alinia, Hossein; Kuo, Sandy; Huang, Karen E; Feldman, Steven R

2014-12-13

There are no definitive treatments of facial redness for rosacea. All treatments aim to alleviate symptoms. Patients' perspectives of two emerging modalities, Low level light therapy and laser treatments are not well characterized. The purpose is to further understand rosacea patients unmet needs about these modalities, Methods: The publicly accessible, online rosacea forum was accessed at august 2013. Stratified random sampling method has done to identify a 10% sample of total 27,051 posts. The Posts were published in the "Laser and IPL therapy" and "Low level light therapy" forums were qualitatively analyzed. Patients discussed a variety of topics, but most commonly discussed effectiveness (34.2%), treatment education (19.3%), and adverse effects (18%). Relationship with the health care provider (9.9%), cost (8.1%), execution of treatments (8.1%) and convenience of treatments (2.5%) were less commonly discussed, but contributed to patients' decisions about utilizing laser and light therapies. Online forums are utilized to fulfill patients' desire for educational, empathic and collaborative relationship. Patients' adherence to laser and light therapies will likely increase if costs are reduced, reduction in redness is consistent with their expectations, and if physicians empower them through education on device choices and managing adverse effects.

Cinacalcet in peritoneal dialysis patients: one-center experience.

PubMed

Conde, Sara Querido; Branco, Patrícia; Sousa, Henrique; Adragão, Teresa; Gaspar, Augusta; Barata, José Diogo

2017-03-01

Secondary hyperparathyroidism is the target of several therapeutic strategies, including the use of cinacalcet. Most studies were done only in hemodialysis patients, with few data from peritoneal dialysis patients. The aim of our work was to evaluate the effectiveness of cinacalcet in secondary hyperparathyroidism in a one-center peritoneal dialysis patients. A retrospective study was performed in 27 peritoneal dialysis patients with moderate to severe secondary hyperparathyroidism (PTHi > 500 pg/mL with normal or elevated serum calcium levels) treated with cinacalcet. Demographic, clinical and laboratory parameters at the beginning of cinacalcet therapy, second, fourth, sixth months after and at the time it was finished were analyzed. Patients were under peritoneal dialysis at 30.99 ± 16.58 months and were treated with cinacalcet for 15.6 ± 13.4 months; 21 (77.8%) patients showed adverse gastrointestinal effects; PTHi levels at the beginning of cinacalcet therapy were 1145 ± 449 pg/mL. The last PTHi levels under cinacalcet therapy was 1131 ± 642 pg/mL. PTHi reduction was statistically significant at 2 months after the beginning of cinacalcet (p = 0.007) but not in the following evaluations. It is necessary the development of new forms of cinacalcet presentation, in order to avoid gastrointestinal effects adverse factors and to improve therapeutic adherence.